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What is the fate of NADH produced in the liver during oxidation of lactic acid?

What is the fate of NADH produced in the liver during oxidation of lactic acid?


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NADH ('reduced NAD') is produced during the oxidation of blood lactate in the liver. Glycolysis requires NAD+ ('oxidised NAD'), whereas gluconeogensis requires NADH. However the NADH is apparently not always used for gluconeogenesis (How is NAD+ used in lactic acid fermentation after it is oxidized from NADH?), i.e. the Cori Cycle does not always operate - so what becomes of the NADH in this case?

My best guess is that, along with the pyruvate, it may be transferred in the blood somehow to do to the site where it is needed, and it will then be taken into the electron transport chain, while the pyruvate will be taken into the Krebs cycle.


The “best guess” in this question is incorrect and the question itself indicates a lack of understanding of the roles of NAD+ and NADH in energy metabolism. (To rectifiy this, Chapters 17 and 18 of Berg et al. are suggested.)

The production of NADH in the oxidation of carbohydrates and fats is the energetic rationale for these processes. Under aerobic conditions the re-oxidation of NADH to NAD+ via the electron transport chain in the mitochondria* generates ATP for the energetic processes of the cell.

The fate of NADH produced by the oxidation of lactate reaching the liver from the blood would be similar under conditions where it is not needed for gluconeogenesis (in the reversal of the GAPDH reaction). In these circumstances it would be reoxidized to NAD+, generating ATP in the mitochondria*.

[Note also that pyruvate is most likely to be oxidized by the liver mitochondria to produce metabolic intermediates and ATP, rather than transferred to the blood. NADH is certainly not transferred to the blood.]

*Advanced Point: Cytoplasmic and Mitochondrial NAD

The statement above, that NADH is “reoxidized to NAD+, generating ATP in the mitochondria”, is correct, but may be taken to imply that the NADH enters the mitochondria. This is not the case becase the NADH and NAD+ cannot pass through the mitochondrial membrane (as @tomd has commented). However the electrons that represent the reduced state of NADH do pass through the membrane. They do this in the guise of other molecules which are reduced in the cytoplasm by NADH in what are known as electron shuttles. The electrons enter the electron transport chain and are finally accepted by molecular oxygen. More detail of shuttles can be found in section 18.5 of Berg et al.


9.3: Fermentation and Regeneration of NAD+

Section summary

This section discusses the process of fermentation. Due to the heavy emphasis in this course on central carbon metabolism, the discussion of fermentation understandably focuses on the fermentation of pyruvate. Nevertheless, some of the core principles that we cover in this section apply equally well to the fermentation of many other small molecules.

The "purpose" of fermentation

The oxidation of a variety of small organic compounds is a process that is utilized by many organisms to garner energy for cellular maintenance and growth. The oxidation of glucose via glycolysis is one such pathway. Several key steps in the oxidation of glucose to pyruvate involve the reduction of the electron/energy shuttle NAD + to NADH. You were already asked to figure out what options the cell might reasonably have to reoxidize the NADH to NAD + in order to avoid consuming the available pools of NAD + and to thus avoid stopping glycolysis. Put differently, during glycolysis, cells can generate large amounts of NADH and slowly exhaust their supplies of NAD + . If glycolysis is to continue, the cell must find a way to regenerate NAD + , either by synthesis or by some form of recycling.

In the absence of any other process&mdashthat is, if we consider glycolysis alone&mdashit is not immediately obvious what the cell might do. One choice is to try putting the electrons that were once stripped off of the glucose derivatives right back onto the downstream product, pyruvate, or one of its derivatives. We can generalize the process by describing it as the returning of electrons to the molecule that they were once removed, usually to restore pools of an oxidizing agent. This, in short, is fermentation. As we will discuss in a different section, the process of respiration can also regenerate the pools of NAD + from NADH. Cells lacking respiratory chains or in conditions where using the respiratory chain is unfavorable may choose fermentation as an alternative mechanism for garnering energy from small molecules.

An example: lactic acid fermentation

An everyday example of a fermentation reaction is the reduction of pyruvate to lactate by the lactic acid fermentation reaction. This reaction should be familiar to you: it occurs in our muscles when we exert ourselves during exercise. When we exert ourselves, our muscles require large amounts of ATP to perform the work we are demanding of them. As the ATP is consumed, the muscle cells are unable to keep up with the demand for respiration, O2 becomes limiting, and NADH accumulates. Cells need to get rid of the excess and regenerate NAD + , so pyruvate serves as an electron acceptor, generating lactate and oxidizing NADH to NAD + . Many bacteria use this pathway as a way to complete the NADH/NAD + cycle. You may be familiar with this process from products like sauerkraut and yogurt. The chemical reaction of lactic acid fermentation is the following:

Pyruvate + NADH &harr lactic acid + NAD +

Figure 1. Lactic acid fermentation converts pyruvate (a slightly oxidized carbon compound) to lactic acid. In the process, NADH is oxidized to form NAD + . Attribution: Marc T. Facciotti (original work)

Energy story for the fermentation of pyruvate to lactate

An example (if a bit lengthy) energy story for lactic acid fermentation is the following:

The reactants are pyruvate, NADH, and a proton. The products are lactate and NAD + . The process of fermentation results in the reduction of pyruvate to form lactic acid and the oxidation of NADH to form NAD + . Electrons from NADH and a proton are used to reduce pyruvate into lactate. If we examine a table of standard reduction potential, we see under standard conditions that a transfer of electrons from NADH to pyruvate to form lactate is exergonic and thus thermodynamically spontaneous. The reduction and oxidation steps of the reaction are coupled and catalyzed by the enzyme lactate dehydrogenase.

A second example: alcohol fermentation

Another familiar fermentation process is alcohol fermentation, which produces ethanol, an alcohol. The alcohol fermentation reaction is the following:

Figure 2. Ethanol fermentation is a two-step process. Pyruvate (pyruvic acid) is first converted into carbon dioxide and acetaldehyde. The second step converts acetaldehyde to ethanol and oxidizes NADH to NAD + . Attribution: Marc T. Facciotti (original work)

In the first reaction, a carboxyl group is removed from pyruvic acid, releasing carbon dioxide as a gas (some of you may be familiar with this as a key component of various beverages). The second reaction removes electrons from NADH, forming NAD + and producing ethanol (another familiar compound&mdashusually in the same beverage) from the acetaldehyde, which accepts the electrons.

Write a complete energy story for alcohol fermentation. Propose possible benefits of this type of fermentation for the single-celled yeast organism.

Fermentation pathways are numerous

While the lactic acid fermentation and alcohol fermentation pathways described above are examples, there are many more reactions (too numerous to go over) that Nature has evolved to complete the NADH/NAD + cycle. It is important that you understand the general concepts behind these reactions. In general, cells try to maintain a balance or constant ratio between NADH and NAD + when this ratio becomes unbalanced, the cell compensates by modulating other reactions to compensate. The only requirement for a fermentation reaction is that it uses a small organic compound as an electron acceptor for NADH and regenerates NAD + . Other familiar fermentation reactions include ethanol fermentation (as in beer and bread), propionic fermentation (it's what makes the holes in Swiss cheese), and malolactic fermentation (it's what gives Chardonnay its more mellow flavor&mdashthe more conversion of malate to lactate, the softer the wine). In Figure 3, you can see a large variety of fermentation reactions that various bacteria use to reoxidize NADH to NAD + . All of these reactions start with pyruvate or a derivative of pyruvate metabolism, such as oxaloacetate or formate. Pyruvate is produced from the oxidation of sugars (glucose or ribose) or other small, reduced organic molecules. It should also be noted that other compounds can be used as fermentation substrates besides pyruvate and its derivatives. These include methane fermentation, sulfide fermentation, or the fermentation of nitrogenous compounds such as amino acids. You are not expected to memorize all of these pathways. You are, however, expected to recognize a pathway that returns electrons to products of the compounds that were originally oxidized to recycle the NAD + /NADH pool and to associate that process with fermentation.

Figure 3. This figure shows various fermentation pathways using pyruvate as the initial substrate. In the figure, pyruvate is reduced to a variety of products via different and sometimes multistep (dashed arrows represent possible multistep processes) reactions. All details are deliberately not shown. The key point is to appreciate that fermentation is a broad term not solely associated with the conversion of pyruvate to lactic acid or ethanol. Source: Marc T. Facciotti (original work)

A note on the link between substrate-level phosphorylation and fermentation

Fermentation occurs in the absence of molecular oxygen (O2). It is an anaerobic process. Notice there is no O2 in any of the fermentation reactions shown above. Many of these reactions are quite ancient, hypothesized to be some of the first energy-generating metabolic reactions to evolve. This makes sense if we consider the following:

  1. The early atmosphere was highly reduced, with little molecular oxygen readily available.
  2. Small, highly reduced organic molecules were relatively available, arising from a variety of chemical reactions.
  3. These types of reactions, pathways, and enzymes are found in many different types of organisms, including bacteria, archaea, and eukaryotes, suggesting these are very ancient reactions.
  4. The process evolved long before O2 was found in the environment.
  5. The substrates, highly reduced, small organic molecules, like glucose, were readily available.
  6. The end products of many fermentation reactions are small organic acids, produced by the oxidation of the initial substrate.
  7. The process is coupled to substrate-level phosphorylation reactions. That is, small, reduced organic molecules are oxidized, and ATP is generated by first a red/ox reaction followed by the substrate-level phosphorylation.
  8. This suggests that substrate-level phosphorylation and fermentation reactions coevolved.

If the hypothesis is correct that substrate-level phosphorylation and fermentation reactions co-evolved and were the first forms of energy metabolism that cells used to generate ATP, then what would be the consequences of such reactions over time? What if these were the only forms of energy metabolism available over hundreds of thousands of years? What if cells were isolated in a small, closed environment? What if the small, reduced substrates were not being produced at the same rate of consumption during this time?

Consequences of fermentation

Imagine a world where fermentation is the primary mode for extracting energy from small molecules. As populations thrive, they reproduce and consume the abundance of small, reduced organic molecules in the environment, producing acids. One consequence is the acidification (decrease in pH) of the environment, including the internal cellular environment. This can be disruptive, since changes in pH can have a profound influence on the function and interactions among various biomolecules. Therefore, mechanisms needed to evolve that could remove the various acids. Fortunately, in an environment rich in reduced compounds, substrate-level phosphorylation and fermentation can produce large quantities of ATP.

It is hypothesized that this scenario was the beginning of the evolution of the F0F1-ATPase, a molecular machine that hydrolyzes ATP and translocates protons across the membrane (we'll see this again in the next section). With the F0F1-ATPase, the ATP produced from fermentation could now allow for the cell to maintain pH homeostasis by coupling the free energy of hydrolysis of ATP to the transport of protons out of the cell. The downside is that cells are now pumping all of these protons into the environment, which will now start to acidify.

If the hypothesis is correct that the F0F1-ATPase also co-evolved with substrate-level phosphorylation and fermentation reactions, then what would happen over time to the environment? While small, reduced organic compounds may have been initially abundant, if fermentation "took off" at some point, then the reduced compounds would run out and ATP might then become scarce as well. That's a problem. Thinking with the design challenge rubric in mind, define the problem(s) facing the cell in this hypothesized environment. What are other potential mechanisms or ways Nature could overcome the problem(s)?


Lactic Acid and the Bloodstream

As lactic acid accumulates inside your muscle cells, it enters your bloodstream. Your liver soaks up the circulating lactate. Later on, while you are resting, your liver is busy oxidizing the lactic acid to pyruvate through a reaction catalyzed by an enzyme called lactate dehydrogenase. The enzyme uses the electrons removed from lactate to reduce a molecule of NAD to NADH. Pyruvate enters small capsule-shaped structures called mitochondria via a transporter, where it may meet with one of several different fates.


Section Summary

If NADH cannot be metabolized through aerobic respiration, another electron acceptor is used. Most organisms will use some form of fermentation to accomplish the regeneration of NAD + , ensuring the continuation of glycolysis. The regeneration of NAD + in fermentation is not accompanied by ATP production therefore, the potential for NADH to produce ATP using an electron transport chain is not utilized.

Additional Self Check Questions

1. Tremetol, a metabolic poison found in white snake root plant, prevents the metabolism of lactate. When cows eat this plant, Tremetol is concentrated in the milk. Humans who consume the milk become ill. Symptoms of this disease, which include vomiting, abdominal pain, and tremors, become worse after exercise. Why do you think this is the case?

2. When muscle cells run out of oxygen, what happens to the potential for energy extraction from sugars and what pathways do the cell use?

Answers

Glossary

anaerobic cellular respiration: the use of an electron acceptor other than oxygen to complete metabolism using electron transport-based chemiosmosis

fermentation: the steps that follow the partial oxidation of glucose via glycolysis to regenerate NAD + occurs in the absence of oxygen and uses an organic compound as the final electron acceptor


Part 3: Glycolysis and fermentation

A) Glycolysis

Glycolysis is the process by which a glucose molecule is converted into two molecules of pyruvate. It typically occurs in the cytoplasm. In addition to 2 pyruvate molecules, each glucose molecule that undergoes glycolysis will also result in the production of 2 NADH and 4 ATP molecules. However, during the process, 2 ATP molecules are consumed. Thus, the net products of glycolysis are 2 pyruvate molecules, 2 NADH, and 2 ATP. (These NADH molecules will be quite useful as electron carriers in the electron transport chain, which we will discuss later.)

The following diagram illustrates every step of glycolysis however, only a handful of these are particularly high yield. While you won’t need to memorize each step of glycolysis and its related enzymes, it may be useful to be familiar with the function of each enzyme.

Figure: An overview of glycolysis. Note that one molecule of glucose (a 6-carbon molecule) yields two molecules of pyruvate (a 3-carbon molecule).

Step 1: Hexokinase/Glucokinase

Glucokinase is found in hepatocytes (liver cells) and pancreatic β-islet cells. It is activated by insulin. Hexokinase, on the other hand, is a bit more universal and found in most tissues. Both enzymes serve the same function: to use ATP to catalyze the irreversible phosphorylation of glucose.

The product of this reaction, glucose 6-phosphate, is now unable to spontaneously diffuse out of the cell. Glucose 6-phosphate also has an inhibitory effect on the hexokinase enzyme.

Step 3: Phosphofructokinase 1 (PFK-1)

Phosphofructokinase 1, also known as PFK-1, catalyzes the rate-limiting step of glycolysis. It uses ATP to catalyze the irreversible conversion of fructose 6-phosphate into fructose 1,6-bisphosphate. This step is highly regulated. Citrate (a metabolic product of aerobic respiration) and ATP have a negative feedback effect on PFK-1.

Why would this be? The presence of citrate and/or ATP indicates that the cell’s energy needs are being met, and thus signals that the glycolysis pathway is not immediately needed. Since this step is an irreversible conversion--and thus requires energy to be performed--shutting down PFK-1 when it is not needed allows the cell to conserve valuable energy.

On the other hand, the presence of AMP (adenosine monophosphate) indicates low energy in the cell and activates PFK-1.

Step 6: G3P dehydrogenase

G3P dehydrogenase catalyzes the reversible conversion of glyceraldehyde 3-phosphate into 1,3-bisphosphoglycerate, which generates one molecule NADH. However, one molecule of glucose (a 6-carbon structure) generates 2 molecules of glyceraldehyde 3-phosphate--so this step yields two molecules of NADH per glucose molecule.

Step 7: Phosphoglycerate kinase

Phosphoglycerate kinase catalyzes the reversible conversion of 1,3-bisphosphoglycerate into 3-phosphoglycerate--or, the removal of a phosphate group from 1,3-bisphosphoglycerate. This generates one ATP per molecule of phosphoglycerate (or 2 ATP per glucose molecule).

Step 10: Pyruvate kinase

The final enzyme of glycolysis, pyruvate kinase, catalyzes the irreversible conversion of phosphoenolpyruvate into pyruvate--or, the removal of a phosphate group from phosphoenolpyruvate. This generates one ATP per molecule of phosphoenolpyruvate (or 2 ATP per glucose molecule).

B) Lactic acid fermentation

Under anaerobic conditions--or, when there is a lack of oxygen--the pyruvate molecules generated by glycolysis will undergo fermentation. During this process, lactate dehydrogenase catalyzes the conversion of pyruvate into lactate (another 3-carbon molecule) and generates NAD+ as a byproduct. Since it is the only enzyme in the process, it is the rate-determining step.

Why would our cells perform lactic acid fermentation, if it does not yield any ATP? The primary purpose of lactic acid fermentation is to replenish the NAD+ that was converted into NADH during glycolysis by glyceraldehyde 3-phosphate dehydrogenase. This makes additional NAD+ available to glycolytic enzymes, so our cells can continue producing 2 ATP at a time through glycolysis.

Lactic acid fermentation is part of a larger pathway known as the lactic acid cycle, or Cori cycle. Lactate generated by the muscles is sent to the liver through the bloodstream. The liver has specialized enzymes that can convert lactate into glucose, which is then sent back to the muscles.

Figure: The Cori cycle allows the recycling of lactate.

C) Gluconeogenesis

Between energy stores available in glycogen and dietary intake, the glucose content in the body is usually sufficient to meet energy needs. However, these sources of energy can easily run out: for instance, during exercise or periods of fasting. How does energy continue to be supplied?

Gluconeogenesis is a metabolic pathway that uses precursors from other sources--for instance, lipids or amino acids--to create glucose. The process can be thought of as the “reverse” of glycolysis: after converting these precursor molecules into pyruvate, several of the same enzymes used in glycolysis will run the reverse reaction to create glucose.

Any reactions that are rate-limiting steps in glycolysis require an additional set of enzymes to catalyze the reverse reaction during gluconeogenesis. Each of these steps requires an additional ATP molecule to proceed spontaneously.


How Cells Derive Energy from Glucose: Metabolic Pathways

Cells use different steps to break down the absorbed glucose to carbon dioxide and water through different enzymatic reactions. The catabolism of glucose occurs in two metabolic pathways: glycolysis and the tricarboxylic acid (TCA also called citric acid or Kreb’s) cycle.

Glycolysis: Enzymes for glycolysis are located in the cytosol of the cell, and glycolysis occurs in this part of the cell. Glycolysis is the breakdown of 6 C glucose into two 3 C end product pyruvates in aerobic metabolism and lactic acid in anaerobic metabolism. It is a catabolic pathway involving oxidation and yields ATP and NADH (reduced NAD) energy. Glycolysis is the pathway by which other sugars (e.g., fructose, galactose) are catabolized by converting them to intermediates of glycolysis. Fructose can be converted to fructose-6-phosphate by hexokinase. Galactose can enter glycolysis by being converted to galactose-1-phosphate followed by conversion (ultimately) to glucose-1-phosphate and subsequently to glucose-6-phosphate (G6P), which is a glycolysis intermediate.

Energy Production Process through Glycolysis: Glycolysis has two phases: an energy investment phase requiring the input of ATP (preparatory phase) and an energy realization phase (pay off) where ATP is made (Figure 5.2). Cells that utilize glucose have an enzyme called hexokinases, which use ATP to phosphorylate the glucose (attaches a phosphorus group) and changes it into G6P. At this point, the cellular “machinery” can begin to process the glucose. Briefly, in the first reaction of glycolysis, hexokinase catalyzes the transfer of phosphate to glucose from ATP, forming glucose-6-phosphate. Thus this step uses ATP, which provides the energy necessary for the reaction to proceed. Glucose-6-phosphate is converted to fructose-6-phosphate and subsequently to fructose-1,6-biphosphate, which is cleaved to dihydroxy acetone phosphate (DHAP) and glyceraldehyde-3-phosphate (G3P). During this process, an additional ATP is required to phosphorylate the intermediate fructose-6-phosphate. Therefore, the “preparation” of glucose results in two molecules of ATP being used for every glucose molecule processed.
During the payoff phase, G3P is further processed to produce pyruvate. During this phase, one NADH and two ATP are produced during the intermediate steps. The DHAP produced can be simply converted into G3P and processed in a similar manner as the first G3P. Therefore, one glucose molecule will result in the production of two NADH, four ATP, and two pyruvate molecules.

Glycolysis: Net Gain of ATP

Figure 5.2. Glycolysis pathway in cytosol Source: Wikipedia

Glycolysis: Overall Functions

ATP Production:
For each molecule of glucose, 2 ATP (preparatory phase) were used and 2 NADH, 4 ATP, and 2 pyruvate molecules (payoff phase) were generated which equals a net production of 2 NADH, 2 ATP, and 2 pyruvate molecules, and the net gain of ATP is 8 per mole of glucose.

Production of Other Intermediates:
Glycolysis provides pyruvate for the TCA cycle, amino acid synthesis through transamination, glucose-6-phosphate (glycogen synthesis), nicotinamide adenine dinucleotide phosphate, (NADPH) (fatty acid synthesis triglyceride synthesis), and dihydroxyacetone phosphate for glycerol synthesis (the backbone of fat).

Fates of Pyruvate in the Animal Body

It is important to discuss the fate of pyruvate generated through glycolysis. Pyruvate has different fates, depending on the conditions of the animal and the cell type.

Fates of Pyruvate

Lactic Acid Production: When oxygen is present, there is plenty of NAD+, so aerobic cells convert pyruvate to acetyl coenzyme A (CoA) for oxidation in the citric acid cycle. When oxygen is absent, NAD+ levels can go down, so to prevent that from happening, lactate dehydrogenase uses NADH and pyruvate is converted to either lactate (animals) or ethanol (bacteria/yeast). Anaerobic conversion of NADH to NAD+ provides much less ATP energy to cells than when oxygen is present. Anaerobic metabolism of glucose generates only two ATP per glucose. Once oxygen is depleted for the cell, another system will convert the lactic acid back to pyruvate and produce glucose.

Acetyl CoA Production:

Acetyl CoA Production: Acetyl CoA production occurs in the aerobic state and serves as the main precursor for the TCA cycle, lipogenesis, and ketogenesis (during negative balance). Acetyl CoA is converted to ATP through different steps in the TCA cycle. During this conversion, the enzyme pyruvate dehydrogenase and different B vitamin–containing coenzymes (thiamine, riboflavin, niacin, pantothenic acid) function through a series of condensation, isomerization, and dehydrogenation reactions and produces several different intermediates that are used for fat or amino acid synthesis.

To generate more energy from the glucose molecule, further biochemical processes occur within the animal body. These include the enzymatic step pyruvate dehydrogenase (PDH), which connects glycolysis (cytosol) with the TCA cycle in the mitochondria. During this step, 3 C pyruvate is converted to an active form of acetic acid called acetyl CoA, and CO2 is produced.

Pyruvic acid is decarboxylated and the 2 H ions are picked up by NAD+ and thus it provides two mole of NADH for each mole of glucose (net = 6 ATP produced). This enzymatic step needs coenzyme A and its activity is highly regulated by the concentration of acetyl CoA, ATP, and NADH.


Unit 7: Cellular Respiration and Energy Metabolism

I. Describe the process of cellular respiration in general terms.

II. Describe the roles of ATP, NAD, and FAD in energy metabolism in the cell.

III. Describe the process of glycolysis.

IV. Describe the formation of acetyl coenzyme A from pyruvic acid.

V. Explain the role of the Krebs cycle in cellular respiration.

VI. Describe the role of the electron transport chain in cellular respiration.

VII. Describe the major steps in the generation of ATP by chemiosmosis.

VIII. Summarize the ATP produced from the breakdown of a single glucose molecule.

IX. Describe the importance of oxygen (O2) in cellular respiration and compare aerobic respiration with lactic acid fermentation.

X. Describe the importance of carbohydrates, lipids and proteins in energy storage and energy availability, and their use during starvation conditions.

XI. Describe the importance of glucose in cellular respiration and ATP production.

XII. Describe the role of lipids and amino acids in ATP production.

XIII. Describe the role of ketone bodies in energy metabolism.

XIV. Describe the relationship between gluconeogenesis, lipid metabolism, and protein catabolism.

XV. Describe the fate of amino acids that are metabolized for ATP production.

XVI. Explain the importance of appropriate nutrient intake for maintaining homeostasis of the body.

Learning Objectives and Guiding Questions

At the end of this unit, you should be able to complete all the following tasks, including answering the guiding questions associated with each task.

I. Describe the process of cellular respiration in general terms.

  1. Define the term “cellular respiration”.
  2. What is the main biological function of cellular respiration?
  3. Determine and write out the overall chemical equation for aerobic cellular respiration.

II. Describe the roles of ATP, NAD, and FAD in energy metabolism in the cell.

  1. Use complete sentences to describe how cells produce:
    • ATP
    • NADH
    • FADH2
  2. Use complete sentences to describe the biological purpose of a cell producing:
    • ATP
    • NADH
    • FADH2

III. Describe the process of glycolysis.

IV. Describe the formation of acetyl coenzyme A from pyruvic acid.

V. Explain the role of the Krebs cycle in cellular respiration.

VI. Describe the role of the electron transport chain in cellular respiration.

VII. Describe the major steps in the generation of ATP by chemiosmosis.

  1. Write a single-sentence summary of the chemical events that occur during each of the following processes:
    • Glycolysis
    • Pyruvic acid oxidation
    • The Krebs (citric acid) cycle
    • The electron transport chain
    • Substrate-level phosphorylation
    • Oxidative phosphorylation
  2. Specify the molecules that are required, consumed, and produced during each of the following processes:
    • Glycolysis
    • Pyruvic acid oxidation
    • The Krebs (citric acid) cycle
    • The electron transport chain
  3. Starting with the arrival of NADH and FADH2 at the electron transport chain, thoroughly describe how the electron transport chain is used to generate ATP.

VIII. Summarize the ATP produced from the breakdown of a single glucose molecule.

  1. At which point(s) during aerobic cellular respiration of one glucose molecule are ATP molecules produced by each of the following processes, and how many ATP molecules are produced by each process?
    • Substrate-level phosphorylation
    • Oxidative phosphorylation

IX. Describe the importance of oxygen (O2) in cellular respiration and compare aerobic respiration and lactic acid fermentation.

  1. For what single main function is oxygen required during cellular respiration?
  2. In the absence of oxygen, how many molecules of ATP can be produced from a single glucose molecule?
  3. Explain why, in the absence of oxygen, the continued generation of ATP from glucose requires the conversion of pyruvic acid to lactic acid.

X. Describe the importance of carbohydrates, lipids and proteins in energy storage and energy availability, and their use during starvation conditions.

  1. Describe and explain the use of carbohydrates, lipids, and proteins for ATP production when in:
    • An absorptive (fed) state.
    • A postabsorptive (fasting) state.
    • Starvation conditions.
  2. Protein molecules contain approximately the same amount of energy per gram as carbohydrates and are found extensively throughout the human body. Explain why it is physiologically important that proteins are used as major sources of chemical energy only after other energy-containing molecules (i.e., carbohydrates and lipids) have been depleted.

XI. Describe the importance of glucose in cellular respiration and ATP production.

  1. Which specific nutrient molecule are all human body cells normally capable of breaking down to generate ATP?

XII. Describe the role of lipids and amino acids in ATP production.

  1. What other nutrient molecules are at least some human body cells capable of breaking down to generate ATP? For each of these nutrient molecules, which body cell types can (or cannot) break it down?

XIII. Describe the role of ketone bodies in energy metabolism.

  1. What types of molecules can be used to produce ketone bodies?
  2. Under what conditions should ketone bodies be produced?
  3. What function do ketone bodies serve in the human body?

XIV. Describe the relationship between gluconeogenesis, lipid metabolism, and protein catabolism.

XV. Describe the fate of amino acids that are metabolized for ATP production.

  1. Name and describe with a one-sentence summary the mechanism(s) that are used to allow body cells to continue generating ATP in the event that:
    • Blood glucose levels decline
    • Glycogen stores in the body decline
    • Lipid stores in the body decline
    • Oxygen is unavailable
  2. Explain the functional reason why, under conditions of low oxygen availability, lactic acid (or lactate) must be produced to allow glycolysis to continue.
  3. Clearly define each of the following terms:
    • Glycolysis
    • Glycogenesis
    • Gluconeogenesis
    • Glycogenolysis
  4. Describe the process in the human body by which some of the energy present in lipid molecules can be used to generate ATP.
    • In which organ(s) and/or cell type(s) can this process occur?
    • Which major steps are involved?
    • Can any of the intermediate molecules be transported to other tissues in a form that will allow the receiving tissues to generate ATP in the absence of glucose?
    • At what stage(s) of cellular respiration can the breakdown products of lipid molecules be used?
  5. Describe the process in the human body by which some of the energy present in amino acids can be used to generate ATP.
    • In which organ(s) and/or cell type(s) can this process occur?
    • Which major step are involved?
    • At what stage(s) of cellular respiration can the breakdown products of amino acids be used?
    • In breaking down amino acids, what potentially toxic chemical is produced that is not produced when a lipid or carbohydrate is broken down? What is the fate of this product?
    • What are the potentially detrimental physiological consequences of breaking down amino acids, rather than glucose, to produce ATP?

XVI. Explain the importance of appropriate nutrient intake for maintaining homeostasis of the body.

  1. List the classes of nutrients that can be broken down to release energy that can be used to produce ATP.
  2. For each of the following chemicals, describe its function in metabolism and name the specific nutrient(s) that must be ingested to produce it:
    • Pyruvate dehydrogenase
    • Nicotinamide adenine dinucleotide (NAD + )
    • Flavin adenine dinucleotide (FAD)
    • Coenzyme A

    Part 1: Carbohydrate Metabolism

    Carbohydrates are organic molecules composed of carbon, hydrogen, and oxygen atoms. The family of carbohydrates includes both sugars (i.e. monosaccharides and disaccharides) and polysaccharides. Glucose and fructose are examples of sugars, and starch, glycogen, and cellulose are all examples of polysaccharides. Polysaccharides are made of multiple monosaccharide molecules. Polysaccharides serve as energy storage (e.g., starch and glycogen) and as structural components (e.g., chitin in insects and cellulose in plants).

    During digestion, carbohydrates are broken down into simple, soluble sugars that can be transported across the intestinal wall into the circulatory system to be transported throughout the body. Carbohydrate digestion begins in the mouth with the action of salivary amylase on starches and ends with monosaccharides being absorbed across the epithelium of the small intestine. Once the absorbed monosaccharides are transported to the tissues, the process of cellular respiration begins (Figure 1). This section will focus first on glycolysis, a process where the monosaccharide glucose is oxidized, releasing the energy stored in its bonds to produce ATP.

    Figure 1. Cellular Respiration. Cellular respiration oxidizes glucose molecules through glycolysis, the Krebs cycle, and oxidative phosphorylation to produce ATP.

    Glycolysis: Glucose is the body’s most readily available source of energy. After digestive processes break polysaccharides down into monosaccharides, including glucose, the monosaccharides are transported across the wall of the small intestine and into the circulatory system, which transports them to the liver. In the liver, hepatocytes either pass the glucose on through the circulatory system or store excess glucose as glycogen. Cells in the body take up the circulating glucose in response to insulin and, through a series of reactions called glycolysis, transfer some of the energy in glucose to a new bond between adenosine diphosphate (ADP) and a third phosphate group to form adenosine triphosphate (ATP) (Figure 2). The last step in glycolysis produces the product pyruvate.

    Glycolysis can be expressed as the following equation:

    Glucose + 2ATP + 2NAD + + 4ADP + 2Pi → 2 Pyruvate + 4ATP + 2NADH + 2H +

    This equation states that glucose – in combination with ATP (a source of chemical energy), nicotinamide adenine dinucleotide (NAD + , a coenzyme that serves as an electron acceptor), and inorganic phosphate – breaks down into two pyruvate molecules, generating four ATP molecules – for a net yield of two ATP – and two energy-containing NADH coenzyme molecules (resulting from adding a hydrogen atom and an extra electron to NAD + ). The NADH that is produced in this process will be used later to produce ATP in the mitochondria. Importantly, by the end of this process, one glucose molecule generates two pyruvate molecules, two high-energy ATP molecules, and two electron-carrying NADH molecules.

    Glycolysis can be divided into two phases: energy consuming (also called chemical priming) and energy yielding. The first phase is the energy-consuming phase, so it requires two ATP molecules to start the reaction for each molecule of glucose. At the end of this phase, the six-carbon sugar is split to form two phosphorylated three-carbon sugars, glyceraldehyde-3-phosphate (G3P) and dihydroxyacetone phosphate (DHAP). DHAP is then converted into glyceraldehyde-3-phosphate.

    The second phase of glycolysis, the energy-yielding phase, harvests the energy contained in G3P, which is further phosphorylated and oxidized. During this step an electron is released that is then picked up by NAD + to create an NADH molecule. NADH is a high-energy molecule, like ATP, but unlike ATP, it is not used as energy currency by the cell. Because there are two glyceraldehyde-3-phosphate molecules, two NADH molecules are synthesized during this step. In a series of reactions leading to pyruvate, the two phosphate groups are then transferred from the molecule to which they are attached to two ADPs to form two ATPs by the process of substrate-level phosphorylation (direct phosphorylation). Thus, glycolysis uses two ATPs but generates four ATPs, yielding a net gain of two ATPs and two molecules of pyruvate. In the presence of oxygen, pyruvate continues on to the Krebs cycle (also called the citric acid cycle or tricarboxylic acid cycle (TCA), where additional energy is extracted and passed on, converted into lactic acid by fermentation or used later for the synthesis of glucose through gluconeogenesis.

    Anaerobic Conditions: When oxygen (O2) is limited or absent, pyruvate enters an anaerobic pathway. In these reactions, pyruvate can be converted into lactic acid. This pathway serves to oxidize NADH into the NAD+ needed by glycolysis. In this reaction, pyruvate replaces oxygen as the final electron acceptor. It accepts the electrons from the NADH produced from glycolysis, regenerating NAD + , and is reduced to form lactic acid. This lactic acid fermentation occurs in most cells of the body when oxygen is limited or mitochondria are absent or nonfunctional. For example, because erythrocytes (red blood cells) lack mitochondria, they must produce their ATP from lactic acid fermentation. This is an effective pathway of ATP production for short periods of time, ranging from seconds to a few minutes. The lactic acid produced diffuses into the plasma and is carried to the liver, where it is converted back into pyruvate or glucose. Similarly, when a person exercises, muscles use ATP faster than oxygen can be delivered to them. They depend on glycolysis and lactic acid production for rapid ATP production.

    Figure 2. Glycolysis Overview. During the energy-consuming phase of glycolysis, two ATPs are consumed, transferring two phosphates to the glucose molecule. The glucose molecule then splits into two three-carbon compounds, each containing a phosphate. During the second phase, an additional phosphate is added to each of the three-carbon compounds. The energy for this endergonic reaction is provided by the removal (oxidation) of two electrons from each three-carbon compound. During the energy-yielding phase, the phosphates are removed from both three-carbon compounds and used to produce four ATP molecules.

    Aerobic Respiration: In the presence of oxygen, pyruvate can enter the Krebs cycle where additional energy is extracted as electrons are transferred from the pyruvate to the acceptors NAD+ and flavin adenine dinucleotide (FAD), with carbon dioxide released as a waste product (Figure 3). The NADH and FADH2 (resulting from the addition of two hydrogen atoms to FAD) pass electrons on to the electron transport chain, which uses the transferred energy to produce ATP by oxidative phosphorylation. As the last step in the electron transport chain, oxygen is the terminal electron acceptor, combining with electrons and hydrogen ions to produce water inside the mitochondria.

    Krebs Cycle (Citric Acid Cycle or Tricarboxylic Acid Cycle): The pyruvate molecules generated during glycolysis are transported across the mitochondrial membrane into the inner mitochondrial matrix, where they are metabolized by enzymes in a pathway called the Krebs cycle (Figure 4). The Krebs cycle is also commonly called the citric acid cycle or the tricarboxylic acid (TCA) cycle. During the Krebs cycle, high-energy molecules, including ATP, NADH, and FADH2, are created. NADH and FADH2 then pass electrons through the electron transport chain in the mitochondria to generate more ATP molecules.

    The three-carbon pyruvate molecule generated during glycolysis moves from the cytoplasm into the mitochondrial matrix, where it is converted into a two-carbon acetyl group and bound to coenzyme A to form an acetyl coenzyme A (acetyl CoA) molecule. This reaction is an oxidative decarboxylation that releases carbon dioxide and transfers two electrons to NAD+ to form NADH. Acetyl CoA enters the Krebs cycle by combining with a four-carbon molecule, oxaloacetate, to form the six-carbon molecule citrate, or citric acid, at the same time releasing the coenzyme A molecule.

    The six-carbon citrate molecule is then converted to a five-carbon molecule and then a four-carbon molecule, ending with oxaloacetate, the beginning of the cycle. Along the way, each citrate molecule will produce one ATP, one FADH2, and three NADH. The FADH2 and NADH will enter the oxidative phosphorylation system located in the inner mitochondrial membrane. In addition, the Krebs cycle supplies the starting materials to process and break down proteins and fats.

    Oxidative Phosphorylation: Oxidative phosphorylation is made up of two closely tied components, the electron transport chain and chemiosmosis. The electron transport chain (ETC) uses the NADH and FADH2 produced by the Krebs cycle to generate a proton gradient. Electrons from NADH and FADH2 are transferred through protein complexes embedded in the inner mitochondrial membrane by a series of enzymatic reactions. The electron transport chain consists of a series of four enzyme complexes (Complex I – Complex IV) and two mobile electron shuttles (ubiquinone and Cytochrome c), which act as electron carriers and proton pumps used to transfer H + ions into the space between the inner and outer mitochondrial membranes (Figure 5). The ETC couples the transfer of electrons between a donor (like NADH) and an electron acceptor (O2) with the transfer of protons (H + ions) across the inner mitochondrial membrane. In the presence of oxygen, energy is passed, stepwise, through the electron carriers to collect gradually the energy needed to attach a phosphate to ADP and produce ATP. The role of molecular oxygen, O2, is as the terminal electron acceptor for the ETC. This means that once the electrons have passed through the entire ETC, they must be passed to another, separate molecule. These electrons, O2, and H + ions from the matrix combine to form new water molecules. This is the basis for your need to breathe in oxygen. Without oxygen, electron flow through the ETC ceases.

    The electrons released from NADH and FADH2 are passed along the chain by each of the carriers, which are reduced when they receive the electron and oxidized when passing it on to the next carrier. Each of these reactions releases a small amount of energy, which is used to pump H+ ions across the inner membrane. The accumulation of these protons in the space between the membranes creates a proton gradient with respect to the mitochondrial matrix.

    Figure 3. Aerobic Respiration Versus Lactic Acid Production. The process of lactic acid fermentation converts glucose into two lactate molecules in the absence of oxygen or within erythrocytes that lack mitochondria. During aerobic respiration, glucose is oxidized into two pyruvate molecules. Figure 4. Krebs Cycle. During the Krebs cycle, each pyruvate that is generated by glycolysis is converted into a two-carbon acetyl CoA molecule. The acetyl CoA is systematically processed through the cycle and produces high-energy NADH, FADH2, and ATP molecules. (Not all material in this figure is examinable.)

    In chemiosmosis, the energy stored in the proton gradient generated by the electron transport chain is used to generate ATP. Embedded in the inner mitochondrial membrane is an amazing protein pore complex called ATP synthase. Effectively, it is a turbine that is powered by the flow of H + ions across the inner membrane down a gradient and into the mitochondrial matrix. As the H + ions traverse the complex, the shaft of the complex rotates. This rotation enables other portions of ATP synthase to encourage ADP and Pi to create ATP.

    Figure 5. Oxidative Phosphorylation. The electron transport chain is a series of electron carriers and ion pumps that are used to pump H + ions out of the inner mitochondrial matrix. The resulting proton gradient then drives ATP production by ATP synthase.

    In accounting for the total number of ATP produced per glucose molecule through aerobic respiration, it is important to remember the following points:

    A net of two ATP are produced through glycolysis (four produced and two consumed during the energy-consuming stage).

    In all phases after glycolysis, the number of ATP, NADH, and FADH2 produced must be multiplied by two to reflect how each glucose molecule produces two pyruvate molecules.

    In the ETC, about 2.5 ATP are produced for every oxidized NADH. However, only about 1.5 ATP are produced for every oxidized FADH2. The electrons from FADH2 produce less ATP, because they start at a lower point in the ETC (Complex II) compared to the electrons from NADH (Complex I) (see Figure 5)

    Therefore, for every glucose molecule that enters aerobic respiration, a possible net total of 32 ATPs are produced (Figure 6). This total represents the maximum potential ATP production per glucose molecule from aerobic cellular respiration.

    Figure 6. Carbohydrate Metabolism. Carbohydrate metabolism involves glycolysis, the Krebs cycle, and the electron transport chain.

    Gluconeogenesis: Gluconeogenesis is the synthesis of new glucose molecules from pyruvate, lactate, glycerol, or some amino acids. This process takes place primarily in the liver during periods of low glucose, that is, under conditions of fasting, starvation, and low carbohydrate diets. So, the question can be raised as to why the body would create something it has just spent a fair amount of effort to break down? Certain key organs, including the brain, can use only glucose as an energy source therefore, it is essential that the body maintain a minimum blood glucose concentration. When the blood glucose concentration falls below that certain point, new glucose is synthesized by the liver to raise the blood concentration to normal.

    As will be discussed as part of lipolysis, fats can be broken down into glycerol, which can be phosphorylated to form dihydroxyacetone phosphate or DHAP. DHAP can either enter the glycolytic pathway or be used by the liver as a substrate for gluconeogenesis.

    Part 2: Lipid Metabolism

    Fats (or triglycerides) within the body are ingested as food or synthesized by adipocytes or hepatocytes from carbohydrate precursors (Figure 8). Lipid metabolism entails the oxidation of fatty acids to either generate energy or synthesize new lipids from smaller constituent molecules. Lipid metabolism is associated with carbohydrate metabolism, as products of glucose (such as acetyl CoA) can be converted into lipids.

    Figure 8. Triglyceride Broken Down into a Monoglyceride. A triglyceride molecule (a) breaks down into a monoglyceride (b).

    Lipolysis: To obtain energy from fat, triglycerides must first be broken down by hydrolysis into their two principal components, fatty acids and glycerol. This process, called lipolysis, takes place in the cytoplasm of adipocytes. Subsequently, the fatty acids and glycerol are released into the bloodstream, to be taken up by tissues such as the muscle, heart and liver. The resulting fatty acids are oxidized by β-oxidation into acetyl CoA, which is used by the Krebs cycle. The glycerol that is released from triglycerides after lipolysis directly enters the glycolysis pathway as DHAP. Because one triglyceride molecule yields three fatty acid molecules with as much as 16 or more carbons in each one, fat molecules yield more energy than carbohydrates and are an important source of energy for the human body. Triglycerides yield more than twice the energy per unit mass when compared to carbohydrates and proteins. Therefore, when glucose levels are low, triglycerides can be converted into acetyl CoA molecules and used to generate ATP through aerobic respiration.

    The breakdown of fatty acids begins in the cytoplasm, where fatty acids are converted into fatty acyl CoA molecules. This fatty acyl CoA is transported to the mitochondrial matrix, where it is broken down and oxidized to acetyl CoA in a process called fatty acid oxidation or beta (β)-oxidation (Figure 10). The newly formed acetyl CoA enters the Krebs cycle and is used to produce ATP in the same way as acetyl CoA derived from pyruvate.

    Ketogenesis: If excessive acetyl CoA is created from the oxidation of fatty acids and the Krebs cycle is overloaded and cannot handle it, the acetyl CoA, in the liver, is diverted to create ketone bodies (Fig. 11).

    Two of these ketone bodies (β-hydroxybutyrate and acetoacetate, and their acid forms β-hydroxybutyric acid and acetoacetatic acid) can serve as a fuel source if glucose levels are too low in the body. Ketone bodies serve as fuel in times of prolonged starvation or when patients suffer from uncontrolled diabetes and cannot utilize most of the circulating glucose. The third ketone body, acetone, is removed by exhalation. One symptom of ketogenesis is that the patient’s breath smells sweet like alcohol. This effect provides one way of telling if a diabetic is properly controlling the disease.

    Figure 10. Breakdown of Fatty Acids. During fatty acid oxidation, triglycerides can be broken down into acetyl CoA molecules and used for energy when glucose levels are low. Figure 11. Ketogenesis. Excess acetyl CoA is diverted from the Krebs cycle to the ketogenesis pathway. This reaction occurs in the mitochondria of liver cells. The result is the production of β-hydroxybutyrate, the primary ketone body found in the blood.

    Ketone Body Oxidation: Organs that have classically been thought to be dependent solely on glucose, such as the brain, can actually use ketone bodies as an alternative energy source. This keeps the brain and other organs, such as the heart, functioning when glucose is limited. Since both β-hydroxybutyric acid and acetoacetatic acid are acids, their presence in blood, can cause acidosis (ketoacidosis), a dangerous condition in diabetics.

    In these organs, ketone bodies are converted to two acetyl CoA molecules each. These acetyl CoA molecules are then processed through the Krebs cycle to generate energy (Figure 12).

    Figure 12. Ketone Oxidation. When glucose is limited, ketone bodies can be oxidized to produce acetyl CoA to be used in the Krebs cycle to generate energy.

    Lipogenesis: When glucose levels are plentiful, the excess acetyl CoA generated by glycolysis and pyruvate oxidation can be converted into fatty acids, triglycerides, cholesterol, steroids, and bile salts. This process, called lipogenesis, creates lipids (fat) from the acetyl CoA and takes place in the cytoplasm of adipocytes (fat cells) and hepatocytes (liver cells) (Figure 13). When you eat more glucose or carbohydrates than your body needs, acetyl CoA is turned into fat. Although there are several metabolic sources of acetyl CoA, it is most commonly derived from glycolysis. Acetyl CoA availability is significant, because it initiates lipogenesis. Lipogenesis begins with acetyl CoA and advances by the subsequent addition of two carbon atoms from another acetyl CoA this process is repeated until fatty acids are the appropriate length. Because this is a bond-creating anabolic process, ATP is consumed. However, the creation of triglycerides and lipids is an efficient way of storing the energy available in carbohydrates. Triglycerides and lipids, high-energy molecules, are stored in adipose tissue until they are needed.

    Figure 13. Lipid Metabolism. Lipids may follow one of several pathways during metabolism. Glycerol and fatty acids follow different pathways.

    Part 3: Protein Metabolism

    Freely available amino acids are used to create proteins. If amino acids exist in excess, the body has no capacity or mechanism for their storage thus, they are converted into glucose or ketone bodies. Amino acid breakdown results in hydrocarbons, which are converted to glucose through gluconeogenesis, and nitrogenous waste, due to the removal of the amino group via deamination (i.e. ammonium, NH4 + ). However, high concentrations of nitrogen are toxic. The urea cycle, a liver process, converts ammonium into urea, facilitating the excretion of excess nitrogen from the body.

    In the urea cycle, ammonium is combined with CO2, resulting in urea and water. The urea is eliminated through the kidneys in the urine.

    Amino acids can also be used as a source of energy, especially in times of starvation. Because the processing of amino acids results in the creation of metabolic intermediates, including pyruvate, acetyl CoA, acetoacyl CoA, oxaloacetate, and α-ketoglutarate, amino acids can serve as a source of energy production through the Krebs cycle (Figure 16). Figure 17 summarizes the pathways of catabolism and anabolism for carbohydrates, lipids, and proteins.

    Part 4: Metabolic States of the Body

    You eat periodically throughout the day however, your organs, especially the brain, need a continuous supply of glucose. How does the body meet this constant demand for energy? Your body processes the food you eat both to use immediately and, importantly, to store as energy for later demands. If there were no method in place to store excess energy, you would need to eat constantly in order to meet energy demands. Distinct mechanisms are in place to facilitate energy storage, and to make stored energy available during times of fasting and starvation.

    Figure 16. Accessing the Energy in Amino Acids. Amino acids can be broken down into precursors for glycolysis or the Krebs cycle. Amino acids (in bold) can enter the cycle through more than one pathway. The points of entry of all the amino acids are not examinable. Figure 17. Catabolic and Anabolic Pathways. Nutrients follow a complex pathway from ingestion through anabolism and catabolism to energy production.

    The Absorptive State: The absorptive state, or the fed state, occurs after a meal when your body is digesting the food and absorbing the nutrients (anabolism exceeds catabolism) (Figure 18). Digestion begins the moment you put food into your mouth, as the food is broken down into its constituent parts to be absorbed through the intestine. The digestion of carbohydrates begins in the mouth, whereas the digestion of proteins and fats begins in the stomach and small intestine. The constituent parts of these carbohydrates, fats, and proteins are transported across the intestinal wall and enter the bloodstream (sugars and amino acids) or the lymphatic system (fats). From the intestines, these systems transport them to the liver, adipose tissue, or muscle cells that will process and use, or store, the energy.

    Depending on the amounts and types of nutrients ingested, the absorptive state can linger for up to 4 hours. The ingestion of food and the rise of glucose concentrations in the bloodstream stimulate pancreatic beta cells to release insulin into the bloodstream, where it initiates the absorption of blood glucose by liver hepatocytes, and by adipose and muscle cells. Insulin also stimulates glycogenesis, the storage of glucose as glycogen, in the liver and muscle cells where it can be used for later energy needs of the body. Insulin also promotes the synthesis of protein in muscle. As you will see, muscle protein can be catabolized and used as fuel in times of starvation.

    If energy is exerted shortly after eating, the dietary fats and sugars that were just ingested will be processed and used immediately for energy. If not, the excess glucose is stored as glycogen in the liver and muscle cells, or as fat in adipose tissue excess dietary fat is also stored as triglycerides in adipose tissues.

    The Postabsorptive State: The postabsorptive state, or the fasting state, occurs when the food has been digested, absorbed, and stored (Figure 19). You commonly fast overnight, but skipping meals during the day puts your body in the postabsorptive state as well. During this state, the body must rely initially on stored glycogen. Glucose levels in the blood begin to drop as it is absorbed and used by the cells. In response to the decrease in glucose, insulin levels also drop. Glycogen and triglyceride storage slows. However, due to the demands of the tissues and organs, blood glucose levels must be maintained in the normal range of 80–120 mg/dL. In response to a drop in blood glucose concentration, the hormone glucagon is released from the alpha cells of the pancreas. Glucagon acts upon the liver cells, where it inhibits glycogenesis and stimulates glycogenolysis, the breakdown of stored glycogen back into glucose. The glucose is released from the liver to be used by the peripheral tissues and the brain. As a result, blood glucose levels begin to rise. The stored glycogen in a well-fed human typically is sufficient to meet the energy needs of the body for several hours. Gluconeogenesis, the production of glucose from non-carbohydrates, will also begin in the liver to replace the glucose that has been used by the peripheral tissues.

    Starvation: When the body is deprived of nourishment for an extended period of time, it goes into “survival mode.” The first priority for survival is to provide enough glucose or fuel for the brain. The second priority is the conservation of amino acids for proteins. Therefore, when glucose is no longer available, the use of ketone bodies as an energy source helps to decrease the demand for glucose, thus minimizing gluconeogenesis in order to maintain body proteins.

    Because glucose levels are very low during starvation, glycolysis will shut off in cells that can use alternative fuels. For example, muscles will switch from using glucose to fatty acids as fuel. As previously explained, fatty acids can be converted into acetyl CoA and processed through the Krebs cycle to make ATP. Pyruvate, lactate, and alanine from muscle cells are not converted into acetyl CoA and used in the Krebs cycle, but are exported to the liver to be used in the synthesis of glucose. As starvation continues, and more glucose is needed, glycerol from fatty acids can be liberated and used as a source for gluconeogenesis.

    After several days of starvation, ketone bodies become the major source of fuel for the heart and other organs. As starvation continues, fatty acids and triglyceride stores are oxidized to create these molecules. This prevents the continued breakdown of proteins that serve as carbon sources for gluconeogenesis, helping to maintain the proper functioning of the body’s muscles. Once these lipid stores are fully depleted, proteins from muscles are released and broken down for glucose synthesis. This leads to muscle wasting, as the body is forced to cannibalize the tissue for survival. Overall survival is dependent on the amount of fat and protein stored in the body.

    Figure 18. Absorptive State. During the absorptive state, the body digests food and absorbs the nutrients. Figure 19. Postabsorptive State. During the postabsorptive state, the body must rely on stored glycogen for energy.


    What is the fate of NADH produced in the liver during oxidation of lactic acid? - Biology

    Campell Biology chapter 9:Cellular respiration

    What is the term for metabolic pathways that release stored energy by breaking down complex molecules?
    A) anabolic pathways
    B) catabolic pathways
    C) fermentation pathways
    D) thermodynamic pathways
    E) bioenergetic pathways

    The molecule that functions as the reducing agent (electron donor) in a redox or oxidation-reduction reaction
    A) gains electrons and gains potential energy.
    B) loses electrons and loses potential energy.
    C) gains electrons and loses potential energy.
    D) loses electrons and gains potential energy.
    E) neither gains nor loses electrons, but gains or loses potential energy.

    When electrons move closer to a more electronegative atom, what happens?
    A) The more electronegative atom is reduced, and energy is released.
    B) The more electronegative atom is reduced, and energy is consumed.
    C) The more electronegative atom is oxidized, and energy is consumed.
    D) The more electronegative atom is oxidized, and energy is released.
    E) The more electronegative atom is reduced, and entropy decreases.

    Why does the oxidation of organic compounds by molecular oxygen to produce CO₂ and water release free energy?
    A) The covalent bonds in organic molecules and molecular oxygen have more kinetic energy than the covalent bonds in water and carbon dioxide.
    B) Electrons are being moved from atoms that have a lower affinity for electrons (such as C) to atoms with a higher affinity for electrons (such as O).
    C) The oxidation of organic compounds can be used to make ATP.
    D) The electrons have a higher potential energy when associated with water and CO₂ than they do in organic compounds.
    E) The covalent bond in O₂ is unstable and easily broken by electrons from organic molecules

    Which of the following statements describes the results of this reaction?
    C₆H₁₂O₆ + 6 O₂ → 6 CO₂ + 6 H₂O + Energy
    A) C₆H₁₂O₆ is oxidized and O₂ is reduced.
    B) O₂ is oxidized and H₂O is reduced.
    C) CO₂ is reduced and O₂ is oxidized.
    D) C₆H₁₂O₆ is reduced and CO₂ is oxidized.
    E) O₂ is reduced and CO₂ is oxidized

    When a glucose molecule loses a hydrogen atom as the result of an oxidation-reduction reaction, the molecule becomes
    A) hydrolyzed.
    B) hydrogenated.
    C) oxidized.
    D) reduced.
    E) an oxidizing agent.

    When a molecule of NAD⁺ (nicotinamide adenine dinucleotide) gains a hydrogen atom (not a proton), the molecule becomes
    A) dehydrogenated.
    B) oxidized.
    C) reduced.
    D) redoxed.
    E) hydrolyzed.

    Which of the following statements describes NAD⁺?
    A) NAD⁺ is reduced to NADH during glycolysis, pyruvate oxidation, and the citric acid cycle.
    B) NAD⁺ has more chemical energy than NADH.
    C) NAD⁺ is oxidized by the action of hydrogenases.
    D) NAD⁺ can donate electrons for use in oxidative phosphorylation.
    E) In the absence of NAD⁺, glycolysis can still function.

    Where does glycolysis take place in eukaryotic cells?
    A) mitochondrial matrix
    B) mitochondrial outer membrane
    C) mitochondrial inner membrane
    D) mitochondrial intermembrane space
    E) cytosol

    The ATP made during glycolysis is generated by
    A) substrate-level phosphorylation.
    B) electron transport.
    C) photophosphorylation.
    D) chemiosmosis.
    E) oxidation of NADH to NAD⁺.

    The oxygen consumed during cellular respiration is involved directly in which process or event?
    A) glycolysis
    B) accepting electrons at the end of the electron transport chain
    C) the citric acid cycle
    D) the oxidation of pyruvate to acetyl CoA
    E) the phosphorylation of ADP to form ATP

    Which process in eukaryotic cells will proceed normally whether oxygen (O₂) is present or absent?
    A) electron transport
    B) glycolysis
    C) the citric acid cycle
    D) oxidative phosphorylation
    E) chemiosmosis

    An electron loses potential energy when it
    A) shifts to a less electronegative atom.
    B) shifts to a more electronegative atom.
    C) increases its kinetic energy.
    D) increases its activity as an oxidizing agent.
    E) moves further away from the nucleus of the atom.

    Why are carbohydrates and fats considered high energy foods?
    A) They have a lot of oxygen atoms.
    B) They have no nitrogen in their makeup.
    C) They can have very long carbon skeletons.
    D) They have a lot of electrons associated with hydrogen.
    E) They are easily reduced.

    Substrate-level phosphorylation accounts for approximately what percentage of the ATP formed by the reactions of glycolysis?
    A) 0%
    B) 2%
    C) 10%
    D) 38%
    E) 100%

    During glycolysis, when each molecule of glucose is catabolized to two molecules of pyruvate, most of the potential energy contained in glucose is
    A) transferred to ADP, forming ATP.
    B) transferred directly to ATP.
    C) retained in the two pyruvates.
    D) stored in the NADH produced.
    E) used to phosphorylate fructose to form fructose 6-phosphate

    In addition to ATP, what are the end products of glycolysis?
    A) CO₂ and H₂O
    B) CO₂ and pyruvate
    C) NADH and pyruvate
    D) CO₂ and NADH
    E) H₂O, FADH₂, and citrate

    The free energy for the oxidation of glucose to CO₂ and water is -686 kcal/mol and the free energy for the reduction of NAD⁺ to NADH is +53 kcal/mol. Why are only two molecules of NADH formed during glycolysis when it appears that as many as a dozen could be formed?
    A) Most of the free energy available from the oxidation of glucose is used in the production of ATP in glycolysis.
    B) Glycolysis is a very inefficient reaction, with much of the energy of glucose released as heat.
    C) Most of the free energy available from the oxidation of glucose remains in pyruvate, one of the products of glycolysis.
    D) There is no CO₂ or water produced as products of glycolysis.
    E) Glycolysis consists of many enzymatic reactions, each of which extracts some energy from the glucose molecule

    Starting with one molecule of glucose, the energy-containing products of glycolysis are
    A) 2 NAD⁺, 2 pyruvate, and 2 ATP.
    B) 2 NADH, 2 pyruvate, and 2 ATP.
    C) 2 FADH₂, 2 pyruvate, and 4 ATP.
    D) 6 CO₂, 2 ATP, and 2 pyruvate.
    E) 6 CO₂, 30 ATP, and 2 pyruvate.

    In glycolysis, for each molecule of glucose oxidized to pyruvate
    A) two molecules of ATP are used and two molecules of ATP are produced.
    B) two molecules of ATP are used and four molecules of ATP are produced.
    C) four molecules of ATP are used and two molecules of ATP are produced.
    D) two molecules of ATP are used and six molecules of ATP are produced.
    E) six molecules of ATP are used and six molecules of ATP are produced.

    A molecule that is phosphorylated
    A) has been reduced as a result of a redox reaction involving the loss of an inorganic phosphate.
    B) has a decreased chemical reactivity it is less likely to provide energy for cellular work.
    C) has been oxidized as a result of a redox reaction involving the gain of an inorganic phosphate.
    D) has an increased chemical potential energy it is primed to do cellular work.
    E) has less energy than before its phosphorylation and therefore less energy for cellular work.

    Which kind of metabolic poison would most directly interfere with glycolysis?
    A) an agent that reacts with oxygen and depletes its concentration in the cell
    B) an agent that binds to pyruvate and inactivates it
    C) an agent that closely mimics the structure of glucose but is not metabolized
    D) an agent that reacts with NADH and oxidizes it to NAD⁺
    E) an agent that blocks the passage of electrons along the electron transport chain

    Why is glycolysis described as having an investment phase and a payoff phase?
    A) It both splits molecules and assembles molecules.
    B) It attaches and detaches phosphate groups.
    C) It uses glucose and generates pyruvate.
    D) It shifts molecules from cytosol to mitochondrion.
    E) It uses stored ATP and then forms a net increase in ATP.

    The transport of pyruvate into mitochondria depends on the proton-motive force across the inner mitochondrial membrane. How does pyruvate enter the mitochondrion?
    A) active transport
    B) diffusion
    C) facilitated diffusion
    D) through a channel
    E) through a pore

    Which of the following intermediary metabolites enters the citric acid cycle and is formed, in part, by the removal of a carbon (CO₂) from one molecule of pyruvate?
    A) lactate
    B) glyceraldehydes-3-phosphate
    C) oxaloacetate
    D) acetyl CoA
    E) citrate

    During cellular respiration, acetyl CoA accumulates in which location?
    A) cytosol
    B) mitochondrial outer membrane
    C) mitochondrial inner membrane
    D) mitochondrial intermembrane space
    E) mitochondrial matrix

    How many carbon atoms are fed into the citric acid cycle as a result of the oxidation of one molecule of pyruvate?
    A) two
    B) four
    C) six
    D) eight
    E) ten

    Carbon dioxide (CO₂) is released during which of the following stages of cellular respiration?
    A) glycolysis and the oxidation of pyruvate to acetyl CoA
    B) oxidation of pyruvate to acetyl CoA and the citric acid cycle
    C) the citric acid cycle and oxidative phosphorylation
    D) oxidative phosphorylation and fermentation
    E) fermentation and glycolysis

    A young animal has never had much energy. He is brought to a veterinarian for help and is sent to the animal hospital for some tests. There they discover his mitochondria can use only fatty acids and amino acids for respiration, and his cells produce more lactate than normal. Of the following, which is the best explanation of his condition?
    A) His mitochondria lack the transport protein that moves pyruvate across the outer mitochondrial membrane.
    B) His cells cannot move NADH from glycolysis into the mitochondria.
    C) His cells contain something that inhibits oxygen use in his mitochondria.
    D) His cells lack the enzyme in glycolysis that forms pyruvate.
    E) His cells have a defective electron transport chain, so glucose goes to lactate instead of to acetyl CoA

    During aerobic respiration, electrons travel downhill in which sequence?
    A) food → citric acid cycle → ATP → NAD⁺
    B) food → NADH → electron transport chain → oxygen
    C) glucose → pyruvate → ATP → oxygen
    D) glucose → ATP → electron transport chain → NADH
    E) food → glycolysis → citric acid cycle → NADH → ATP

    What fraction of the carbon dioxide exhaled by animals is generated by the reactions of the citric acid cycle, if glucose is the sole energy source?
    A) 1/6
    B) 1/3
    C) 1/2
    D) 2/3
    E) 100/100

    Where are the proteins of the electron transport chain located?
    A) cytosol
    B) mitochondrial outer membrane
    C) mitochondrial inner membrane
    D) mitochondrial intermembrane space
    E) mitochondrial matrix

    In cellular respiration, the energy for most ATP synthesis is supplied by
    A) high energy phosphate bonds in organic molecules.
    B) a proton gradient across a membrane.
    C) converting oxygen to ATP.
    D) transferring electrons from organic molecules to pyruvate.
    E) generating carbon dioxide and oxygen in the electron transport chain.

    During aerobic respiration, which of the following directly donates electrons to the electron transport chain at the lowest energy level?
    A) NAD+
    B) NADH
    C) ATP
    D) ADP + Pi
    E) FADH2

    The primary role of oxygen in cellular respiration is to
    A) yield energy in the form of ATP as it is passed down the respiratory chain.
    B) act as an acceptor for electrons and hydrogen, forming water.
    C) combine with carbon, forming CO₂.
    D) combine with lactate, forming pyruvate.
    E) catalyze the reactions of glycolysis

    Inside an active mitochondrion, most electrons follow which pathway?
    A) glycolysis → NADH → oxidative phosphorylation → ATP → oxygen
    B) citric acid cycle → FADH₂ → electron transport chain → ATP
    C) electron transport chain → citric acid cycle → ATP → oxygen
    D) pyruvate → citric acid cycle → ATP → NADH → oxygen
    E) citric acid cycle → NADH → electron transport chain → oxygen

    During aerobic respiration, H₂O is formed. Where does the oxygen atom for the formation of the water come from?
    A) carbon dioxide (CO₂)
    B) glucose (C₆H₁₂O₆)
    C) molecular oxygen (O₂)
    D) pyruvate (C₃H₃O₃-)
    E) lactate (C₃H₅O₃-)

    In chemiosmotic phosphorylation, what is the most direct source of energy that is used to convert ADP + Pi to ATP?
    A) energy released as electrons flow through the electron transport system
    B) energy released from substrate-level phosphorylation
    C) energy released from movement of protons through ATP synthase, against the electrochemical gradient
    D) energy released from movement of protons through ATP synthase, down the electrochemical gradient
    E) No external source of energy is required because the reaction is exergonic.

    Energy released by the electron transport chain is used to pump H⁺ into which location in eukaryotic cells?
    A) cytosol
    B) mitochondrial outer membrane
    C) mitochondrial inner membrane
    D) mitochondrial intermembrane space
    E) mitochondrial matrix

    The direct energy source that drives ATP synthesis during respiratory oxidative phosphorylation in eukaryotic cells is
    A) oxidation of glucose to CO₂ and water.
    B) the thermodynamically favorable flow of electrons from NADH to the mitochondrial electron transport carriers.
    C) the final transfer of electrons to oxygen.
    D) the proton-motive force across the inner mitochondrial membrane.
    E) the thermodynamically favorable transfer of phosphate from glycolysis and the citric acid cycle intermediate molecules of ADP

    When hydrogen ions are pumped from the mitochondrial matrix across the inner membrane and into the intermembrane space, the result is the
    A) formation of ATP.
    B) reduction of NAD⁺.
    C) restoration of the Na⁺/K⁺ balance across the membrane.
    D) creation of a proton-motive force.
    E) lowering of pH in the mitochondrial matrix.

    Where is ATP synthase located in the mitochondrion?
    A) cytosol
    B) electron transport chain
    C) outer membrane
    D) inner membrane
    E) mitochondrial matrix

    It is possible to prepare vesicles from portions of the inner mitochondrial membrane. Which one of the following processes could still be carried on by this isolated inner membrane?
    A) the citric acid cycle
    B) oxidative phosphorylation
    C) glycolysis and fermentation
    D) reduction of NAD⁺
    E) both the citric acid cycle and oxidative phosphorylation

    How many oxygen molecules (O₂) are required each time a molecule of glucose (C₆H₁₂O₆) is completely oxidized to carbon dioxide and water via aerobic respiration,?
    A) 1
    B) 3
    C) 6
    D) 12
    E) 30

    Which of the following produces the most ATP when glucose (C₆H₁₂O₆) is completely oxidized to carbon dioxide (CO₂) and water?
    A) glycolysis
    B) fermentation
    C) oxidation of pyruvate to acetyl CoA
    D) citric acid cycle
    E) oxidative phosphorylation (chemiosmosis)

    Approximately how many molecules of ATP are produced from the complete oxidation of two molecules of glucose (C₆H₁₂O₆) in aerobic cellular respiration?
    A) 2
    B) 4
    C) 15
    D) 30-32
    E) 60-64

    The synthesis of ATP by oxidative phosphorylation, using the energy released by movement of protons across the membrane down their electrochemical gradient, is an example of
    A) active transport.
    B) an endergonic reaction coupled to an exergonic reaction.
    C) a reaction with a positive ΔG .
    D) osmosis.
    E) allosteric regulation

    Chemiosmotic ATP synthesis (oxidative phosphorylation) occurs in
    A) all cells, but only in the presence of oxygen.
    B) only eukaryotic cells, in the presence of oxygen.
    C) only in mitochondria, using either oxygen or other electron acceptors.
    D) all respiring cells, both prokaryotic and eukaryotic, using either oxygen or other electron acceptors.
    E) all cells, in the absence of respiration.

    If a cell is able to synthesize 30 ATP molecules for each molecule of glucose completely oxidized by carbon dioxide and water, how many ATP molecules can the cell synthesize for each molecule of pyruvate oxidized to carbon dioxide and water?
    A) 0
    B) 1
    C) 12
    D) 14
    E) 15

    What is proton-motive force?
    A) the force required to remove an electron from hydrogen
    B) the force exerted on a proton by a transmembrane proton concentration gradient
    C) the force that moves hydrogen into the intermembrane space
    D) the force that moves hydrogen into the mitochondrion
    E) the force that moves hydrogen to NAD⁺

    In liver cells, the inner mitochondrial membranes are about five times the area of the outer mitochondrial membranes. What purpose must this serve?
    A) It allows for an increased rate of glycolysis.
    B) It allows for an increased rate of the citric acid cycle.
    C) It increases the surface for oxidative phosphorylation.
    D) It increases the surface for substrate-level phosphorylation.
    E) It allows the liver cell to have fewer mitochondria

    Brown fat cells produce a protein called thermogenin in their mitochondrial inner membrane. Thermogenin is a channel for facilitated transport of protons across the membrane. What will occur in the brown fat cells when they produce thermogenin?
    A) ATP synthesis and heat generation will both increase.
    B) ATP synthesis will increase, and heat generation will decrease.
    C) ATP synthesis will decrease, and heat generation will increase.
    D) ATP synthesis and heat generation will both decrease.
    E) ATP synthesis and heat generation will stay the same

    In a mitochondrion, if the matrix ATP concentration is high, and the intermembrane space proton concentration is too low to generate sufficient proton-motive force, then
    A) ATP synthase will increase the rate of ATP synthesis.
    B) ATP synthase will stop working.
    C) ATP synthase will hydrolyze ATP and pump protons into the intermembrane space.
    D) ATP synthase will hydrolyze ATP and pump protons into the matrix.

    Which catabolic processes may have been used by cells on ancient Earth before free oxygen became available?
    A) glycolysis and fermentation only
    B) glycolysis and the citric acid cycle only
    C) glycolysis, pyruvate oxidation, and the citric acid cycle
    D) oxidative phosphorylation only
    E) glycolysis, pyruvate oxidation, the citric acid cycle, and oxidative phosphorylation, using an electron acceptor other than oxygen

    Which of the following normally occurs regardless of whether or not oxygen (O₂) is present?
    A) glycolysis
    B) fermentation
    C) oxidation of pyruvate to acetyl CoA
    D) citric acid cycle
    E) oxidative phosphorylation (chemiosmosis)

    Which of the following occurs in the cytosol of a eukaryotic cell?
    A) glycolysis and fermentation
    B) fermentation and chemiosmosis
    C) oxidation of pyruvate to acetyl CoA
    D) citric acid cycle
    E) oxidative phosphorylation

    Which metabolic pathway is common to both cellular respiration and fermentation?
    A) the oxidation of pyruvate to acetyl CoA
    B) the citric acid cycle
    C) oxidative phosphorylation
    D) glycolysis
    E) chemiosmosis

    The ATP made during fermentation is generated by which of the following?
    A) the electron transport chain
    B) substrate-level phosphorylation
    C) chemiosmosis
    D) oxidative phosphorylation
    E) aerobic respiration

    In the absence of oxygen, yeast cells can obtain energy by fermentation, resulting in the production of
    A) ATP, CO₂, and ethanol (ethyl alcohol).
    B) ATP, CO₂, and lactate.
    C) ATP, NADH, and pyruvate.
    D) ATP, pyruvate, and oxygen.
    E) ATP, pyruvate, and acetyl CoA.

    In alcohol fermentation, NAD⁺ is regenerated from NADH by
    A) reduction of acetaldehyde to ethanol (ethyl alcohol).
    B) oxidation of pyruvate to acetyl CoA.
    C) reduction of pyruvate to form lactate.
    D) oxidation of ethanol to acetyl CoA.
    E) reduction of ethanol to pyruvate.

    One function of both alcohol fermentation and lactic acid fermentation is to
    A) reduce NAD⁺ to NADH.
    B) reduce FAD⁺ to FADH₂.
    C) oxidize NADH to NAD⁺.
    D) reduce FADH₂ to FAD⁺.
    E) do none of the above.

    An organism is discovered that thrives both in the presence and absence of oxygen in the air. Curiously, the consumption of sugar increases as oxygen is removed from the organism's environment, even though the organism does not gain much weight. This organism
    A) must use a molecule other than oxygen to accept electrons from the electron transport chain.
    B) is a normal eukaryotic organism.
    C) is photosynthetic.
    D) is an anaerobic organism.
    E) is a facultative anaerobe.

    Which statement best supports the hypothesis that glycolysis is an ancient metabolic pathway that originated before the last universal common ancestor of life on Earth?
    A) Glycolysis is widespread and is found in the domains Bacteria, Archaea, and Eukarya.
    B) Glycolysis neither uses nor needs O₂.
    C) Glycolysis is found in all eukaryotic cells.
    D) The enzymes of glycolysis are found in the cytosol rather than in a membrane-enclosed organelle.
    E) Ancient prokaryotic cells, the most primitive of cells, made extensive use of glycolysis long before oxygen was present in Earth's atmosphere.

    Why is glycolysis considered to be one of the first metabolic pathways to have evolved?
    A) It produces much less ATP than does oxidative phosphorylation.
    B) It does not involve organelles or specialized structures, does not require oxygen, and is present in most organisms.
    C) It is found in prokaryotic cells but not in eukaryotic cells.
    D) It relies on chemiosmosis, which is a metabolic mechanism present only in the first cells' prokaryotic cells.
    E) It requires the presence of membrane-enclosed cell organelles found only in eukaryotic cells

    When an individual is exercising heavily and when the muscle becomes oxygen-deprived, muscle cells convert pyruvate to lactate. What happens to the lactate in skeletal muscle cells?
    A) It is converted to NAD⁺.
    B) It produces CO₂ and water.
    C) It is taken to the liver and converted back to pyruvate.
    D) It reduces FADH₂ to FAD⁺.
    E) It is converted to alcohol.

    When skeletal muscle cells are oxygen-deprived, the heart still pumps. What must the heart muscle cells be able to do?
    A) derive sufficient energy from fermentation
    B) continue aerobic metabolism when skeletal muscle cannot
    C) transform lactate to pyruvate again
    D) remove lactate from the blood
    E) remove oxygen from lactate

    When skeletal muscle cells undergo anaerobic respiration, they become fatigued and painful. This is now known to be caused by
    A) buildup of pyruvate.
    B) buildup of lactate.
    C) increase in sodium ions.
    D) increase in potassium ions.
    E) increase in ethanol.

    A mutation in yeast makes it unable to convert pyruvate to ethanol. How will this mutation affect these yeast cells?
    A) The mutant yeast will be unable to grow anaerobically.
    B) The mutant yeast will grow anaerobically only when given glucose.
    C) The mutant yeast will be unable to metabolize glucose.
    D) The mutant yeast will die because they cannot regenerate NAD⁺ from NAD.
    E) The mutant yeast will metabolize only fatty acids

    You have a friend who lost 7 kg (about 15 pounds) of fat on a regimen of strict diet and exercise. How did the fat leave her body?
    A) It was released as CO₂ and H₂O.
    B) It was converted to heat and then released.
    C) It was converted to ATP, which weighs much less than fat.
    D) It was broken down to amino acids and eliminated from the body.
    E) It was converted to urine and eliminated from the body.

    Phosphofructokinase is an important control enzyme in the regulation of cellular respiration. Which of the following statements correctly describes phosphofructokinase activity?
    A) It is inhibited by AMP.
    B) It is activated by ATP.
    C) It is activated by citrate, an intermediate of the citric acid cycle.
    D) It catalyzes the conversion of fructose 1,6-bisphosphate to fructose 6-phosphate, an early step of glycolysis.
    E) It is an allosteric enzyme.

    Phosphofructokinase is an allosteric enzyme that catalyzes the conversion of fructose 6-phosphate to fructose 1,6-bisphosphate, an early step of glycolysis. In the presence of oxygen, an increase in the amount of ATP in a cell would be expected to
    A) inhibit the enzyme and thus slow the rates of glycolysis and the citric acid cycle.
    B) activate the enzyme and thus slow the rates of glycolysis and the citric acid cycle.
    C) inhibit the enzyme and thus increase the rates of glycolysis and the citric acid cycle.
    D) activate the enzyme and increase the rates of glycolysis and the citric acid cycle.
    E) inhibit the enzyme and thus increase the rate of glycolysis and the concentration of citrate

    Even though plants carry on photosynthesis, plant cells still use their mitochondria for oxidation of pyruvate. When and where will this occur?
    A) in photosynthetic cells in the light, while photosynthesis occurs concurrently
    B) in nonphotosynthesizing cells only
    C) in cells that are storing glucose only
    D) in all cells all the time
    E) in photosynthesizing cells in the light and in other tissues in the dark

    In vertebrate animals, brown fat tissue's color is due to abundant blood vessels and capillaries. White fat tissue, on the other hand, is specialized for fat storage and contains relatively few blood vessels or capillaries. Brown fat cells have a specialized protein that dissipates the proton-motive force across the mitochondrial membranes. Which of the following might be the function of the brown fat tissue?
    A) to increase the rate of oxidative phosphorylation from its few mitochondria
    B) to allow the animals to regulate their metabolic rate when it is especially hot
    C) to increase the production of ATP
    D) to allow other membranes of the cell to perform mitochondrial functions
    E) to regulate temperature by converting most of the energy from NADH oxidation to heat

    What is the purpose of beta oxidation in respiration?
    A) oxidation of glucose
    B) oxidation of pyruvate
    C) feedback regulation
    D) control of ATP accumulation
    E) breakdown of fatty acids

    Where do the catabolic products of fatty acid breakdown enter into the citric acid cycle?
    A) pyruvate
    B) malate or fumarate
    C) acetyl CoA
    D) α-ketoglutarate
    E) succinyl CoA

    What carbon sources can yeast cells metabolize to make ATP from ADP under anaerobic conditions?
    A) glucose
    B) ethanol
    C) pyruvate
    D) lactic acid
    E) either ethanol or lactic acid

    High levels of citric acid inhibit the enzyme phosphofructokinase, a key enzyme in glycolysis. Citric acid binds to the enzyme at a different location from the active site. This is an example of
    A) competitive inhibition.
    B) allosteric regulation.
    C) the specificity of enzymes for their substrates.
    D) an enzyme requiring a cofactor.
    E) positive feedback regulation.

    During intense exercise, as skeletal muscle cells go into anaerobiosis, the human body will increase its catabolism of
    A) fats only.
    B) carbohydrates only.
    C) proteins only.
    D) fats, carbohydrates, and proteins.
    E) fats and proteins only.

    Yeast cells that have defective mitochondria incapable of respiration will be able to grow by catabolizing which of the following carbon sources for energy?
    A) glucose
    B) proteins
    C) fatty acids
    D) glucose, proteins, and fatty acids
    E) Such yeast cells will not be capable of catabolizing any food molecules, and will therefor

    Which step in Figure 9.1 shows a split of one molecule into two smaller molecules?
    A) A
    B) B
    C) C
    D) D
    E) E

    In which step in Figure 9.1 is an inorganic phosphate added to the reactant?
    A) A
    B) B
    C) C
    D) D
    E) E

    Which step in Figure 9.1 is a redox reaction?
    A) A
    B) B
    C) C
    D) D
    E) E

    Which portion of the pathway in Figure 9.1 involves an endergonic reaction?
    A) A
    B) B
    C) C
    D) D
    E) E

    Which portion of the pathway in Figure 9.1 contains a phosphorylation reaction in which ATP is the phosphate source?
    A) A
    B) B
    C) C
    D) D
    E) E

    Starting with one molecule of isocitrate and ending with fumarate, how many ATP molecules can be made through substrate-level phosphorylation (see Figure 9.2)?
    A) 1
    B) 2
    C) 11
    D) 12
    E) 24

    Carbon skeletons for amino acid biosynthesis are supplied by intermediates of the citric acid cycle. Which intermediate would supply the carbon skeleton for synthesis of a five-carbon amino acid (see Figure 9.2)?
    A) succinate
    B) malate
    C) citrate
    D) α-ketoglutarate
    E) isocitrate

    For each mole of glucose (C₆H₁₂O₆) oxidized by cellular respiration, how many moles of CO₂ are released in the citric acid cycle (see Figure 9.2)?
    A) 2
    B) 4
    C) 6
    D) 12
    E) 3

    If pyruvate oxidation is blocked, what will happen to the levels of oxaloacetate and citric acid in the citric acid cycle shown in Figure 9.2?
    A) There will be no change in the levels of oxaloacetate and citric acid.
    B) Oxaloacetate will decrease and citric acid will accumulate.
    C) Oxaloacetate will accumulate and citric acid will decrease.
    D) Both oxaloacetate and citric acid will decrease.
    E) Both oxaloacetate and citric acid will accumulate.

    Starting with citrate, which of the following combinations of products would result from three acetyl CoA molecules entering the citric acid cycle (see Figure 9.2)?
    A) 1 ATP, 2 CO₂, 3 NADH, and 1 FADH₂
    B) 2 ATP, 2 CO₂, 3 NADH, and 3 FADH₂
    C) 3 ATP, 3 CO₂, 3 NADH, and 3 FADH₂
    D) 3 ATP, 6 CO₂, 9 NADH, and 3 FADH₂
    E) 38 ATP, 6 CO₂, 3 NADH, and 12 FADH

    For each molecule of glucose that is metabolized by glycolysis and the citric acid cycle (see Figure 9.2), what is the total number of NADH + FADH₂ molecules produced?
    A) 4
    B) 5
    C) 6
    D) 10
    E) 12

    Figure 9.3 shows the electron transport chain. Which of the following is the combination of substances that is initially added to the chain?
    A) oxygen, carbon dioxide, and water
    B) NAD⁺, FAD, and electrons
    C) NADH, FADH₂, and protons
    D) NADH, FADH₂, and O₂
    E) oxygen and protons

    Which of the following most accurately describes what is happening along the electron transport chain in Figure 9.3?
    A) Chemiosmosis is coupled with electron transfer.
    B) Each electron carrier alternates between being reduced and being oxidized.
    C) ATP is generated at each step.
    D) Energy of the electrons increases at each step.
    E) Molecules in the chain give up some of their potential energy.

    Which of the protein complexes labeled with Roman numerals in Figure 9.3 will transfer electrons to O₂?
    A) complex I
    B) complex II
    C) complex III
    D) complex IV
    E) All of the complexes can transfer electrons to O₂.

    What happens at the end of the chain in Figure 9.3?
    A) 2 electrons combine with a proton and a molecule of NAD⁺.
    B) 2 electrons combine with a molecule of oxygen and two hydrogen atoms.
    C) 4 electrons combine with a molecule of oxygen and 4 protons.
    D) 4 electrons combine with four hydrogen and two oxygen atoms.
    E) 1 electron combines with a molecule of oxygen and a hydrogen atom.

    In the presence of oxygen, the three-carbon compound pyruvate can be catabolized in the citric acid cycle. First, however, the pyruvate (1) loses a carbon, which is given off as a molecule of CO₂, (2) is oxidized to form a two-carbon compound called acetate, and (3) is bonded to coenzyme A.

    These three steps result in the formation of
    A) acetyl CoA, O₂, and ATP.
    B) acetyl CoA, FADH₂, and CO₂.
    C) acetyl CoA, FAD, H₂, and CO₂.
    D) acetyl CoA, NADH, H⁺, and CO₂.
    E) acetyl CoA, NAD⁺, ATP, and CO₂.

    In the presence of oxygen, the three-carbon compound pyruvate can be catabolized in the citric acid cycle. First, however, the pyruvate (1) loses a carbon, which is given off as a molecule of CO₂, (2) is oxidized to form a two-carbon compound called acetate, and (3) is bonded to coenzyme A.

    Why is coenzyme A, a sulfur-containing molecule derived from a B vitamin, added?
    A) because sulfur is needed for the molecule to enter the mitochondrion
    B) in order to utilize this portion of a B vitamin which would otherwise be a waste product from another pathway
    C) to provide a relatively unstable molecule whose acetyl portion can be readily transferred to a compound in the citric acid cycle
    D) because it drives the reaction that regenerates NAD⁺
    E) in order to remove one molecule of CO₂

    Exposing inner mitochondrial membranes to ultrasonic vibrations will disrupt the membranes. However, the fragments will reseal "inside out." These little vesicles that result can still transfer electrons from NADH to oxygen and synthesize ATP. If the membranes are agitated further, however, the ability to synthesize ATP is lost.

    After the first disruption, when electron transfer and ATP synthesis still occur, what must be present?
    A) all of the electron transport proteins as well as ATP synthase
    B) all of the electron transport system and the ability to add CoA to acetyl groups
    C) the ATP synthase system
    D) the electron transport system
    E) plasma membranes like those bacteria use for respiration

    Exposing inner mitochondrial membranes to ultrasonic vibrations will disrupt the membranes. However, the fragments will reseal "inside out." These little vesicles that result can still transfer electrons from NADH to oxygen and synthesize ATP. If the membranes are agitated further, however, the ability to synthesize ATP is lost.

    After the further agitation of the membrane vesicles, what must be lost from the membrane?
    A) the ability of NADH to transfer electrons to the first acceptor in the electron transport chain
    B) the prosthetic groups like heme from the transport system
    C) cytochromes
    D) ATP synthase, in whole or in part
    E) the contact required between inner and outer membrane surfaces

    Exposing inner mitochondrial membranes to ultrasonic vibrations will disrupt the membranes. However, the fragments will reseal "inside out." These little vesicles that result can still transfer electrons from NADH to oxygen and synthesize ATP. If the membranes are agitated further, however, the ability to synthesize ATP is lost.

    These inside-out membrane vesicles
    A) will become acidic inside the vesicles when NADH is added.
    B) will become alkaline inside the vesicles when NADH is added.
    C) will make ATP from ADP and i if transferred to a pH 4 buffered solution after incubation in a pH 7 buffered solution.
    D) will hydrolyze ATP to pump protons out of the interior of the vesicle to the exterior.
    E) will reverse electron flow to generate NADH from NAD⁺ in the absence of oxygen.

    The immediate energy source that drives ATP synthesis by ATP synthase during oxidative phosphorylation is the
    A) oxidation of glucose and other organic compounds.
    B) flow of electrons down the electron transport chain.
    C) affinity of oxygen for electrons.
    D) H⁺ concentration across the membrane holding ATP synthase.
    E) transfer of phosphate to ADP

    Which metabolic pathway is common to both fermentation and cellular respiration of a glucose molecule?
    A) the citric acid cycle
    B) the electron transport chain
    C) glycolysis
    D) synthesis of acetyl CoA from pyruvate
    E) reduction of pyruvate to lactate

    In mitochondria, exergonic redox reactions
    A) are the source of energy driving prokaryotic ATP synthesis.
    B) are directly coupled to substrate-level phosphorylation.
    C) provide the energy that establishes the proton gradient.
    D) reduce carbon atoms to carbon dioxide.
    E) are coupled via phosphorylated intermediates to endergonic processes.

    The final electron acceptor of the electron transport chain that functions in aerobic oxidative phosphorylation is
    A) oxygen.
    B) water.
    C) NAD⁺.
    D) pyruvate.
    E) ADP

    What is the oxidizing agent in the following reaction?
    Pyruvate + NADH + H⁺ → Lactate + NAD⁺
    A) oxygen
    B) NADH
    C) NAD⁺
    D) lactate
    E) pyruvate

    When electrons flow along the electron transport chains of mitochondria, which of the following changes occurs?
    A) The pH of the matrix increases.
    B) ATP synthase pumps protons by active transport.
    C) The electrons gain free energy.
    D) The cytochromes phosphorylate ADP to form ATP.
    E) NAD⁺ is oxidized.

    Most CO₂ from catabolism is released during
    A) glycolysis.
    B) the citric acid cycle.
    C) lactate fermentation.
    D) electron transport.
    E) oxidative phosphorylation


    Lactic Acid Fermentation

    The fermentation method used by animals and some bacteria like those in yogurt is lactic acid fermentation (Figure 1). This occurs routinely in mammalian red blood cells and in skeletal muscle that does not have enough oxygen to allow aerobic respiration to continue (such as in muscles after hard exercise). The chemical reaction of lactic acid fermentation is the following:

    The build-up of lactic acid causes muscle stiffness and fatigue. In muscles, lactic acid produced by fermentation must be removed by the blood circulation and brought to the liver for further metabolism. Once the lactic acid has been removed from the muscle and is circulated to the liver, it can be converted back to pyruvic acid and further catabolized (broken down) for energy.

    Note that the purpose of this process is not to produce lactic acid (which is a waste product and is excreted from the body). The purpose is to convert NADH back into NAD + so that glycolysis can continue so that the cell can produce 2 ATP per glucose.

    Figure 1 Lactic acid fermentation is common in muscles that have become exhausted by use.


    Glycogen: Chemistry & Metabolism | Polyose | Organisms | Biology

    In this article we will discuss about:- 1. Chemistry of Glycogen 2. Amount and Distribution of Glycogen 3. Mobilization 4. Formation 5. Metabolism.

    Chemistry of Glycogen:

    Glycogen is called animal starch because it is in this form that glucose remains stored in the liver and muscles. Glycogen is branched polysaccharides (amylopectin type) consisting of hundreds of glucose units linked together by glucosidic linkages, i.e., α-1, 4′ linkage and 1, 6′ linkage which are formed by specific enzymes—uridine diphosphate glucose (UDPG)—pyrophosphorylase, glycogen synthetase and amylo-(1, 4′ —1, 6′)- transglucosidase respectively.

    Glycogen is soluble in water and makes an opalescent solution and gives red colour with iodine. Glycogen liberates more energy than the corresponding weight of glucose. It does not diffuse into the intracellular fluid, as it exerts no osmotic pressure. It may be easily broken down into glucose by enzymes present in the liver.

    Amount and Distribution of Glycogen:

    In a normal adult about 700 gm of glycogen is present in the body, about 300 gm in liver and 400 gm in muscles. Liver and muscles are the chief storehouses. All growing tissues can store glycogen. Consequently, they are present in large amounts in the placenta in its early stage, the foetal muscles, and the yeast, etc. In the foetal muscles it may be as much as 40% of the total dried solids. Oyster is very rich in glycogen and is a good source for its manufacture.

    Glycogen in any tissue is not a static quantity. It is being constantly used up and re-synthesised. So that at any time the glycogen of the tissue should be considered as a balance between the constant production and loss. Liver glycogen is most mobile. It is the first to be formed and is also the first to be mobilized. Muscle glycogen is much slower to move. There are remarkable differences between the metabolism of liver glycogen and muscle glycogen.

    Mobilization of Glycogen:

    Glycogen is formed both in the liver and muscles (Fig. 10.8).

    When blood sugar tends to fall, liver glycogen is converted into glucose and mobilized in the blood stream (Fig. 10.9).

    Thus blood sugar is maintained. In muscular exercise, starvation, exposure to cold and such other conditions, in which extra energy is demand­ed, liver glycogen is mobilized. This action is helped by certain hormones such as adrenaline (epinephrine), glucagon, thyroxine, growth or somatotrophic hormone (STH) of anterior pituitary, etc. Stimulation of the sympathetic has same function. It is antagonised by insulin. Insulin helps glycogenesis in liver and prevents glycogenolysis.

    The former process is the breakdown of glycogen to glucose whereas the latter is the process of break­down of glycogen or glucose to pyruvic acid (anaerobic) which is further oxidized to CO2 and H2O (aer­obic) through TCA cycle. In both the processes, glycogen is converted to glucose-6-phosphate and in the process of glycogenolysis glucose-6-phosphate is splitted into glucose and Pi by phosphatase whereas in the process of glycolysis glucose-6-phosphate is converted further into fructose-6-phosphate by phosphohexose isomerase.

    Glycogen is broken down to glucose-1-phosphate, catalysed by the enzyme phosphorylase-a. (active form). Phosphorylase exists in an inactive form, phosphorylase. b. Cyclic AMP (CAMP or 3′-5′-AMP) donates a phosphate group and converts it into an active form, phosphorylase- a. An enzyme, adenyl cyclase, helps in the formation of cyclic AMP from ATP which is accelerated by glucagon and adrenaline (epinephrine). The glucose-l-phosphate is converted into glucose-6-phosphate, catalyzed by the enzyme phosphoglucomutase. The enzyme phosphohexo isomerase converts glucose-6-phosphate to fructose-6-phosphate.

    Formation of Glycogen (Glycogenesis):

    In the process of glycogenesis, glucose is phosphorylated to glucose-6-phosphate by hexokinase (glucokinase) in presence of a phosphate donor, ATP a common to the first reaction in the glycolytic path of glucose metabolism. Glucose-6 phosphate is transformed into glucose-1-phosphate, catalysed by the enzyme phosphoglucomutase.

    In the next step glucose-1-phosphate reacts with uridine triphosphate (UTP) to form uridine diphosphate glucose (activated glucose units as UDPG) and inorganic pyrophosphate (PPi). This reaction is catalysed by enzyme UDPG – pyrophosphorylase.

    An enzyme UDPG – glycogen transglucosylase (glycogen synthetase) helps in the addition of glucose residue present in its activated form (UDPG) to a pre-existing glycogen chain at non-reducing outer end of the molecule (glycogen) so that glycogen tree is elongated successively due to the 1, 4′ linkage formation. Thus uridine diphosphate (UDP) is liberated and re-synthesised with the help of ATP – UDP + ATP ADP + UTP.

    A second enzyme, called branching enzyme [amylo-(1, 4′-1,6′) – transglucosidase] transfers a part of the 1, 4′-chain to adjacent chain to form α-1, 6′ linkage and helps in glycogen synthesis by forming a branch point (1, 6′ linkage ) in the molecule.

    Pathway of Formation of Pyruvic Acid:

    Fructose-6-phosphate accepts another phosphate group from ATP and is transformed into fructose-1-6-diphosphate. This reaction is influenced by the enzyme 6-phosphofructokinase. Another enzyme aldolase breaks down the above hexose diphosphate into dihydroxyacetone phosphate and glyceral dehyde-3-phosphate each con­taining 3 carbon atoms (triosephosphate).

    Enzyme triosephosphate isomerase keeps the above two triosephosphates in equilibrium. Glyceraldehyde-3-phosphate is then dehydrogenated by triosephosphate dehydrogenase into 1-3-diphosphoglycerate, the hydrogen being accepted by NAD. Phosphorylation also takes place at this stage and requires inorganic phosphate (Pi). Diphosphoglycerate then donates one high energy phosphate to ADP to convert it into ATP and it itself is transformed into 3-phosphoglycerate.

    This reaction is catalysed by the en­zyme, ATP phosphoglyceric transphosphorylase (phosphoglyceric acid kinase). Phosphoglyceromutase then transforms 3-phosphoglycerate to 2-phosphoglycerate and enolase converts it into 2-phosphoenolpyruvate. Phosphoenolpyruvate is spontaneously converted to pyruvate which is oxidised further to CO2 and H2O through TCA cycle if aerobic condition exists or otherwise reduced to lactic acid.

    ATP-phosphopyruvic transphosphorylase (py­ruvic acid kinase) then transfers one energy-rich (∼) phosphate bond from phosphoenolpyruvate to ADP to form ATP and pyruvic acid. Other monosaccharides (galactose, fructose, and mannose) gain their entrance in the glycolytic pathway as indicated in the Figure 10.10. Citric Acid Cycle or Krebs Cycle:

    The citric acid cycle is one of the most important biochemical mechanisms of oxidation of the activated metab­olites and it is perhaps the major terminal pathway of biological oxidation in all animal tissues. The activated metabolites, which are few in number derived from carbohydrate, protein, and fat, are oxidised by the elec­tron-transport chain and most of the utilisable energy (ATP) are produced for the organism.

    The activated metabolites, which are derived from different foodstuffs (Fig. 10.11), are given below:

    The components, included in this cycle, are interrelated by oxidation and reduction, and other reactions which produce 2CO2, H2O and energy ATP. In case of carbohydrate, the pyruvic acid which is formed by glycolytic path of oxidation enters this cycle by first being transformed into acetyl CoA.

    This cycle is known as Krebs (citric acid) cycle after the English biochemist H.A. Krebs who first formulated and proposed the mechanism. Citric acid being one of the member of the cycle and some of the members contains these carboxylised groups so this cycle is also known as citric acid cycle and tricarboxylic acid (TCA) cycle.

    Acetyl CoA or Active Acetate Formation:

    In presence of six factors, i.e., Mg ++ , NAD, thiamine pyrophosphate, lipoic acid, FAD and coenzyme A, the pyruvic oxidase along with enzyme complex converts pyruvate to active acetate as a result of oxidative decarboxylation and as a result the NADH2 is formed which is reconverted to NAD by electron-transport chain. It enters into the TCA cycle.

    A condensing enzyme, citrate synthetase, helps in the condensation of acetyl CoA with oxalo-acetate to form citrate. Citrate first by a process of dehydration is converted into cis-aconitate which again by a process of rehydration is transformed into iso-citrate. The enzyme aconitase catalyses the reaction at both the two steps, so-citrate in presence of the enzyme iso-citrate dehydrogenase is then dehydrogenated to oxalosuccinate. NAD or NADP acts as a hydrogen-acceptor and is converted into NADH2 or NADPH2.

    An enzyme oxalosuccinate decarboxylase in presence of Mn ++ removes CO2 from oxalosuccinate which is thus converted into α-ketoglutarate. A process of oxidative decarboxylation, similar to that in the conversion of pyruvate to acetyl CoA, transforms a-ketoglutarate to succinyl CoA catalysed by α-ketoglutaric oxidase which also requires coenzyme A, lipoic acid and NAD acting as hydrogen-acceptor.

    Succinyl CoA, while it being converted into succinate, provides energy for synthesis of GTP (guanosine-5′-triphosphate) from GDP (guanosine-5′-diphosphate). So GTP in turn supplies energy for synthesis of ATP from ADP while it is reconverted to GDP. Thus succinyl CoA supplies ultimately energy for the synthesis of ATP.

    [The enzyme thiophorase present in tissues, other than liver, can help in the conversion of succinyl CoA succinate.] Enzyme succinate dehydrogenase converts succinate to fumarate, the hydrogen is transferred directly to flavoprotein (FAD) converting it into FADH2. Fumarase helps in the addition of water to fumarate, malate is formed in this process. Oxaloacetate is regenerated from malate under the influence of malate dehydrogenase, NAD again is the hydrogen-acceptor (Fig. 10.12).

    Pentose Phosphate Pathway (PPP) or Pentose Cycle or Hexose Monophosphate (HMP) Shunt or Phosphogluconate Oxidative path or Warburg-Dickens-Lipmann Path:

    This pathway of glucose metabolism takes place in liver, mammary gland, testis, adrenal cortex and leucocytes. Glucose-6-phosphate derived from different sources is dehydrogenated by glucose-6-phosphate dehydrogenase into 6-phospho-gluconolactone which, through several steps described in the Figure 10.10, is ultimately con­verted into sedoheptulose-7-phosphate and enters again into the main glycolytic pathway at fructose-6-phosphate and glyceraldehyde-3-phosphate.

    The formation of sedoheptulose-7-phosphate is catalysed by transketolase whereas the breakdown is catalysed by the enzyme transaldolase. The transketolase and transaldolase reactions are important in this path which is responsible for conversion of aldehydes to ketones and vice versa, as well as lower sugars to higher sugars and vice versa.

    The physiological benefits in the cycle are as follows:

    i. Synthesis of pentose to be required for the synthesis of nucleotides.

    ii. Pentoses can enter into the glycolytic path and it itself may be oxidized in pentose phosphate pathway (PPP).

    iii. Hexose (glucose-fructose) may be burnt in this PPP or may supply pentoses.

    iv. NADPH2 formed in the PPP, is utilized in the fat and steroid synthesis.

    v. Energy formed in this path is 36 ATP per molecule of glucose if all the NADPH, are oxidized in the mitochondria to NADP.

    vi. The oxidation of glucose (Fig. 10.13) in this path is independent of TCA cycle components.

    vi. Components of PPP may enter into the path of formation of glucuronic acid an ascorbic acid (vitamin C).

    Metabolism of Glycogen:

    I. Metabolism of Glycogen in Liver:

    Sources of Liver Glycogen:

    Glycogenesis (formation of glycogen) in the liver can take place from the following:

    i. From Carbohydrates and the Related Substances:

    For instance, glucose, ga­lactose, fructose, mannose, lactic acid (from muscles or otherwise), pyruvic acid, methyl glyoxal, etc. Lactic acid of muscles is carried through blood stream to the liver where it is converted into glycogen very readily. It is believed that pentose does not form glycogen.

    The antiketogenic amino acids (e.g., glycine, alanine, aspartic acid and glutamic acid, etc.) can read­ily form glucose through TCA cycle or reversible glycolytic path or both, as the case may be, as seen in diabetes mellitus. In diabetes mellitus the G: N ratio increased indicating the glucose is formed from protein (neoglucogenesis). It is reasonable to believe that this glucose may be available for glycogen formation.

    The glycerol part of fats is converted into glucose from which glycogen may be derived.

    Functions of Liver Glycogen:

    i. Liver glycogen is a ready source of glucose supply in the blood.

    ii. It helps in the de-toxicating mechanism in the liver.

    iii. It protects the liver from the toxic effects of arsenic, carbon tetrachloride, etc.

    iv. If the liver glycogen level is high, ketone body formation and rate of deamination of amino acids are depressed.

    II. Metabolism of Glycogen in Muscles:

    Muscle contains about 0.5%-1.0% of glycogen as opposed to 5% in the liver. But due to greater amount of muscles in the body, the total quantity is higher and is about 400 gm or approximately equal depending on the total muscle mass of the body.

    1. Glycogenesis in Muscles:

    Muscle glycogen can be derived from the following sources:

    Which is obviously taken from the blood stream?

    Which is produced in the muscle during muscular contraction? The major part (4/5ths) of the lactic acid produced during exercise is reconverted into glycogen. A small part of it (1/5th) is oxidised into carbon dioxide and water through TCA cycle.

    The conversion of lactic acid into glycogen in the muscle is comparatively much slower than in the liver. So that during heavy muscular exercise, a large amount of lactic acid is produced in the muscles. A good part of it diffuses into the blood stream and is brought to liver where it is readily reconverted into glycogen. Probably glycogen is not produced in the muscles from proteins and carbohydrates.

    2. Glycolysis in Muscles:

    Glycolysis is the process of breakdown of glycogen or glucose in muscles and other tissues into pyruvic and lactic acids (Embdert-Meyerhof glycolytic pathway). Glyco­gen leaves the liver in the form of glucose, but it leaves the muscles in the form of pyru­vic and lactic acids. The difference is proba­bly due to the fact that, the enzyme systems and the chemical reaction in the liver and muscles are not the same.

    Lactic acid that emerges from the muscles is carried to liver through blood stream where it is reconvert­ed into glycogen. This glycogen is again mo­bilised in the form of glucose which enters into the blood stream. Muscles take up this glucose from the blood stream and recover its lost glycogen. This cyclic process of cir­culation of carbohydrate in different forms in different tissues is known as Cori cycle through which muscle and liver glycogens become readily interchangeable (Fig. 10.16).

    Glycogen, in other tissues excepting liver, exhibits the same pattern of breakdown as in the muscles.