Chapter 22: AEROBIC RESPIRATION AND ENERGY PRODUCTION
How many molecules of ATP are produced by the complete degradation of glucose via glycolysis, the citric acid cycle, and oxidative phosphorylation?
The net yield of ATP produced by the complete oxidation of glucose is 36 ATP per glucose
The reaction catalyzed by citrate synthase is a condensation reaction. Define the term condensation
A condensation is a reaction in which aldehydes or ketones react to form larger molecules.
Why would a deficiency of a-ketoglutarate dehydrogenase cause chronic lactic acidosis?
A deficiency of α-ketoglutarate dehydrogenase is characterized by chronic lactic acidosis. The reason for this is that the citric acid cycle cannot provide the energy demands of the body, and the body must rely on glycolysis and lactate fermentation for most of its energy needs. Without α-ketoglutarate dehydrogenase, α-ketoglutarate cannot be converted to succinyl CoA and CO2. However, α-ketoglutarate and alanine can be converted to pyruvate and glutamate by the enzyme alanine transaminase. Lactate dehydrogenase reduces pyruvate to lactate, further contributing to lactic acidosis.
Write the equation for the conversion of isocitrate to a-ketoglutarate, and circle the chemical change that reveals the type of reaction that is occurring
A dehydrogenation reaction is an oxidation reaction in which protons and electrons are removed from a molecule.
What is the function of a transaminase?
A transaminase is an enzyme that catalyzes the transfer of an amino group from an amino acid to a keto acid.
What molecule serves as a signal to increase the rate of the reactions of the citric acid cycle?
ADP
Why are ADP and ATP efficient effector molecules for allosteric enzymes that regulate a biochemical pathway such as the citric acid cycle?
ADP and ATP are efficient effector molecules for allosteric enzymes that regulate biochemical pathways. When ATP is an end product of a biochemical pathway, high amounts of this product serve as negative effectors so that additional ATP is not produced when it is not needed. In addition, when ATP levels are low, ADP levels are high. In this case, ADP is able to serve as a positive effector and increase the biochemical pathway's rate of ATP production.
alanine to pyruvate
ATP Total = 15 ATP
What is the name of the enzyme that catalyzes ATP synthesis in mitochondria?
ATP synthase is the enzyme that catalyzes the synthesis of ATP in the mitochondria.
What does the term aerobic respiration mean?
Aerobic respiration is the oxygen requiring degradation of fuel molecules and production of ATP.
Why are allosteric enzymes an efficient means to regulate a biochemical pathway?
Allosteric enzymes are an efficient means to regulate a biochemical pathway because they bind to effectors, such as ATP or ADP, that alter the shape of the enzyme active site, either stimulating the rate of the reaction or inhibiting the reaction
What is the role of vitamin B6 in transamination?
Pyridoxal phosphate is derived from vitamin B6. Transaminases require the coenzyme pyridoxal phosphate.
Structure of urea
1 NH₂ from Aspartate 1 NH₂ from free NH₃ 1 C from CO₂
What is the energy source used for the urea cycle?
Three ATP are hydrolyzed to provide the energy for the urea cycle.
Which pathway produces more ATP? Explain.
Thus, aerobic respiration harvests nearly 40% of the potential energy of glucose, and anaerobic glycolysis harvests only about 2% of the potential energy of glucose.
Explain the mechanism of transamination
Transaminase binds to the amino acid in its active site. Then, the a-amino group is transferred to pyridoxal phosphate, producing pyridoxamine phosphate. The amino group is then transferred to an a-keto acid.
What chemical transformation is carried out by transaminases?
Transaminases transfer amino groups from amino acids to ketoacids.
What is the net yield of ATP for anaerobic glycolysis?
Two ATP per glucose
Compare the number of molecules of ATP produced by glycolysis to the number of ATP molecules produced by oxidation of glucose by aerobic respiration.
Two ATP per glucose (net yield) are produced in glycolysis, whereas the complete oxidation of glucose in aerobic respiration (glycolysis, the citric acid cycle, and oxidative phosphorylation) results in the production of 36 ATP per glucose.
Under what metabolic conditions is pyruvate converted to acetyl CoA
Under aerobic conditions pyruvate is converted to acetyl CoA.
In the reaction catalyzed by pyruvate dehydrogenase, pyruvate is also oxidized. What substance is reduced when pyruvate is oxidized? What is the product of that reduction reaction?
When pyruvate is oxidized, NAD+ is reduced, producing NADH.
Arginine is converted into
a-Ketoglutarate Nine ATP
Into which citric acid cycle intermediate is each of the following amino acids converted? b. Glutamate
a-Ketoglutarate. 9 atp
a-ketoglutarate dehydrogenase
a-ketoglutarate to succinyl-CoA. Oxidoreductase
Into which citric acid cycle intermediate is each of the following amino acids converted? a. Alanine
a. Pyruvate
citrate synthase
acetyl CoA to citrate a transferase
Phenylalanine is converted to
acetyl coa. two-carbon fragments of phenylalanine are converted to acetyl CoA. For each of these, the energy yield is 12 ATP.
Why is the glutamate family of transaminases so important?
because the ketoacid corresponding to glutamate is a-ketoglutarate, one of the citric acid cycle intermediates. This provides a link between the citric acid cycle and amino acid metabolism. These transaminases provide amino groups for amino acid synthesis and collect amino groups during catabolism of amino acids
Aconitase
citrate to isocitrate Isomerase
isocitrate dehydrogenase
isocitrate to alpha-ketoglutarate. Oxidoreductase
malate dehydrogenase
malate to oxaloacetate -oxidoreductase
Aspartate is converted to
oxaloacetate. No ATP is provided directly. However, this provides a supply of oxaloacetate for use in the citric acid cycle for the continued oxidation of food molecules.
succinate dehydrogenase
succinate to fumarate oxidoreductase
Threonine is converted to
succinate. Five ATP
Succinyl CoA synthase
succinyl-CoA to succinate Hydrolase
How many ions of NAD+ are reduced to molecules of NADH during one turn of the citric acid cycle?
three
Is the following statement true or false? If false, rewrite the statement to make it accurate. Acetyl CoA transfers an acetyl group from pyruvate to citrate
true
Define the term allosteric enzyme.
An allosteric enzyme is one that has an effector binding site and an active site. Effector binding can change the shape of the active site, causing it to be active or inactive
Explain how the citric acid cycle serves as an amphibolic pathway
An amphibolic pathway is a metabolic pathway that functions both in anabolism and catabolism. The citric acid cycle is amphibolic because it has a catabolic function—it completely oxidizes the acetyl group carried by acetyl CoA to provide electrons for ATP synthesis. Because citric acid cycle intermediates are precursors for the biosynthesis of many other molecules, it also serves a function in anabolism.
What is the function of an anaplerotic reaction?
An anaplerotic reaction is one that replenishes an essential intermediate, such as oxaloacetate, so that a critical biochemical pathway, like the citric acid cycle, can continue to function.
Define the term effector
An effector is a molecule that binds to the active site of an allosteric enzyme and either activates or inactivates it, thereby turning the enzyme on or off.
What is meant by the term oxidative phosphorylation?
Oxidative phosphorylation is the process by which the energy of electrons harvested from oxidation of a fuel molecule is used to phosphorylate ADP to produce ATP.
What is the terminal electron acceptor in aerobic respiration?
Oxygen.
Define the term cristae
Cristae are the folds of the inner mitochondrial membrane. The electron transport system and ATP synthase are embedded in these membranes.
In the reaction catalyzed by pyruvate dehydrogenase, pyruvate is decarboxylated. What is meant by the term decarboxylation?
Decarboxylation is a chemical reaction in which a carboxyl group is removed from a molecule.
Explain why deficiencies of citric acid cycle enzymes cause hypotonia.
Deficiencies of citric acid cycle enzymes cause hypotonia because there is insufficient ATP.
What is the role of pyridoxal phosphate in transamination reactions?
During transamination reactions, the a-amino group is transferred to the coenzyme pyridoxal phosphate. In the last part of the reaction, the a-amino group is transferred from pyridoxal phosphate to an a-keto acid.
What kinds of proteins are found in the inner mitochondrial membrane?
Embedded within the inner mitochondrial membrane are transport proteins that move fuel molecules and H+ into the mitochondrial matrix. The electron carriers of the electron transport system and ATP synthase, the multisubunit enzyme that makes ATP, are also located in the inner mitochondrial membrane.
What is the importance of the regulation of the citric acid cycle?
Energy-harvesting pathways, such as the citric acid cycle, must be responsive to the energy needs of the cell. If the energy requirements are high, as during exercise, the reactions must speed up. If energy demands are low and ATP is in excess, the reactions of the pathway slow down.
A bacterial culture is given 14C-labeled pyruvate as its sole source of carbon and energy. The following is the structure of the radiolabeled pyruvate.
First, pyruvate is converted to acetyl CoA. Then, citrate is formed from oxaloacetate and the radiolabeled acetyl CoA.
Fumarase
Fumarate --> Malate - hydration -lyase
Fumarase converts fumarate to malate. Explain this reaction in terms of the chemistry of alcohols and alkenes
Fumarate contains an alkene carbon-carbon double bond. Addition of water to the double bond of fumarate gives malate. The enzyme fumarase catalyzes this reaction. When water is added to the alkene double bond, one of the carbons forms a new bond to —OH, and the other carbon forms a new bond to —H. As a result, the alkene becomes an alcohol.
What biochemical reaction is catalyzed by glutamate dehydrogenase?
Glutamate dehydrogenase catalyzes the oxidative deamination of the amino acid glutamate, producing ammonium ion and -ketoglutarate.
Are the following statements true or false? If false, rewrite the statements to make them accurate. Glycolysis and the citric acid cycle are aerobic processes. These anabolic processes occur in the mitochondria and the cytoplasm, respectively.
Glycolysis is an anaerobic process that occurs in the cytoplasm. The citric acid cycle is an aerobic process that occurs in the mitochondria.
What metabolic condition is produced if the urea cycle does not function properly?
Hyperammonemia
What is hyperammonemia? How are mild forms of this disease treated ?
Hyperammonemia is an elevation of the concentration of ammonium ions in the body. It is caused by a deficiency of urea cycle enzymes. The mild form of this genetic disease can be treated with a low protein diet.
What is the chemical meaning of the term decarboxylation? Give an example of a decarboxylase.
In a decarboxylation reaction, a carboxylate group is removed from a substrate and released as CO2.
At which steps in the citric acid cycle do oxidationreduction reactions occur?
In the citric acid cycle oxidation reactions occur at step 3 (conversion of isocitrate to -ketoglutarate), step 4 (conversion of -ketoglutarate to succinyl CoA), step 6 (conversion of succinate to fumarate), and step 8 (oxidation of malate to produce oxaloacetate).
In the oxidation of succinate to fumarate, what is the structural evidence that an oxidation reaction has occurred? What functional groups are involved?
In this reaction, two H are removed from succinate. In organic chemistry and biochemistry, loss of H indicates that oxidation has occurred
To what class of enzymes does dinucleotide diphosphokinase belong? Explain your answer.
It is a kinase because it transfers a phosphoryl group from one molecule to another. Kinases are a specific type of transferase.
Describe the evidence that suggests that mitochondria evolved from free-living bacteria.
Just like bacteria, mitochondria have their own DNA and protein synthesizing machinery and make some of their own proteins. They also grow and divide like bacteria. The fact that mitochondria have two membranes with very different properties also suggests that they were once free-living bacteria. Perhaps the inner membrane evolved from the original bacterial membrane and the outer membrane evolved from the membrane of the cell that "captured" it.
How do the mitochondria differ from the other components of eukaryotic cells?
Mitochondria are different than other organelles because they are surrounded by two membranes, they have their own genetic information, make some of their own proteins, and they are self-replicating.
What is the function of the mitochondria?
Mitochondria are the organelles responsible for aerobic respiration.
What molecules serve as signals to decrease the rate of the reactions of the citric acid cycle?
Molecules such as ATP, acetyl CoA, NADH, and succinyl CoA all serve as negative allosteric effectors of individual enzymes in the citric acid cycle.
Why is myoglobinuria associated with genetic disorders of the enzymes of the citric acid cycle?
Muscle cells have a high energy (ATP) demand and the citric acid cycle produces large amounts of ATP. When there is a genetic disorder of one of the enzymes of the citric acid cycle, muscle cells may die as a result of insufficient energy. When the cells die, myoglobin is released into the blood and urine. This condition is called myoglobinuria.
Explain why mutations of the citric acid cycle enzymes frequently appear first in the central nervous system.
Mutations of the citric acid cycle enzymes frequently appear first in the central nervous system because of the high energy (ATP) demands of this tissue.
Write a balanced chemical equation for the reduction of NAD +
NAD+ H:2 −−−−→ NADH
How many molecules of FAD are converted to FADH2 during one turn of the citric acid cycle?
One FAD is reduced to FADH2 in one turn of the citric acid cycle
What is the function of oxaloacetate in the citric acid cycle?
Oxaloacetate is the "acceptor" of the acetyl group of acetyl CoA. It becomes covalently joined to the acetyl group. By this reaction the acetyl group enters the citric acid cycle for the final stages of its oxidation.
What general type of reaction is occurring in the conversion of isocitrate to a-ketoglutarate?
Oxidation reduction
What vitamins are required for acetyl CoA production from pyruvate?
Pyruvate is converted to acetyl CoA by the pyruvate dehydrogenase complex. This huge enzyme complex requires four coenzymes, each of which is made from a different vitamin. The four coenzymes are thiamine pyrophosphate (made from thiamine), FAD (made from riboflavin), NAD1 (made from niacin), and coenzyme A (made from the vitamin pantothenic acid). The coenzyme lipoamide is also involved in this reaction.
Explain the role of allosteric enzymes in control of the citric acid cycle.
Several of the enzymes of the citric acid cycle are allosteric enzymes that are either inhibited or stimulated by binding of an effector. Typically the effectors are molecules such as ATP, that would indicate that the cell has sufficient energy, or ADP, that would indicate that the ATP supply is low. In order for the enzymes to respond appropriately to the energy needs of the cell, it is logical that ATP would serve as a negative allosteric effector and ADP would serve as a positive allosteric effector.
The pair of reactions catalyzed by aconitase results in the conversion of isocitrate to its isomer citrate. What are isomers?
Structural isomers are molecules having the same molecular formula but different molecular structures.
To what class of enzymes does succinate dehydrogenase belong? Explain your answer
Succinate dehydrogenase catalyzes the oxidation of succinate to produce fumarate. Thus, the enzyme is an oxidoreductase.
What substance is the source of the carbonyl group?
The carbonyl group of urea is derived from CO2 .
What four allosteric enzymes or enzyme complexes are responsible for the regulation of the citric acid cycle?
The citric acid cycle is regulated by the following four enzymes or enzyme complexes: pyruvate dehydrogenase complex, citrate synthase, isocitrate dehydrogenase, and the a-ketoglutarate dehydrogenase complex.
How could a deficiency of riboflavin, thiamine, niacin, or pantothenic acid reduce the amount of ATP the body can produce?
The coenzymes NAD+, FAD, thiamine pyrophosphate, and coenzyme A are required by the pyruvate dehydrogenase complex for the conversion of pyruvate to acetyl CoA. These coenzymes are synthesized from the vitamins niacin, riboflavin, thiamine, and pantothenic acid, respectively. If the vitamins are not available, the coenzymes will not be available and pyruvate cannot be converted to acetyl CoA. Because the complete oxidation of the acetyl group of acetyl CoA produces the vast majority of the ATP for the body, ATP production would be severely inhibited by a deficiency of any of these vitamins.
The enzyme aconitase catalyzes the isomerization of citrate into isocitrate. Discuss the two reactions catalyzed by aconitase in terms of the chemistry of alcohols and alkenes
The conversion of citrate to cis-aconitate is an example of the dehydration of an alcohol to produce an alkene (double bond). The conversion of cis-aconitate to isocitrate is an example of the hydration of an alkene, that is, the addition of water to the double bond, to produce an alcohol (-OH).
What is the cellular location of the electron transport systems?
The electron carriers of the electron transport system are located in the inner mitochondrial membrane.
Define the term electron transport system
The electron transport system is a series of electron transport proteins embedded in the inner mitochondrial membrane that accept high-energy electrons from NADH and FADH2 and transfer them in stepwise fashion to molecular oxygen (O2 ).
What is the function of the electron transport systems of the mitochondria?
The electron transport system passes electrons harvested during oxidation of fuel molecules to molecular oxygen. At three sites, protons are pumped from the mitochondrial matrix into the intermembrane compartment. Thus, the electron transport system builds the high-energy H1 reservoir that provides energy for ATP synthesis
What biochemical processes occur in the matrix space of the mitochondria?
The final oxidation of carbohydrates, amino acid carbon skeletons, and fatty acids occur in the mitochondrial matrix. The pathways that carry out these reactions are the citric acid cycle and b-oxidation of fatty acids.
What is the function of acetyl CoA in the citric acid cycle?
The function of acetyl CoA in the citric acid cycle is to bring the two-carbon remnant (acetyl group) of pyruvate from glycolysis and transfer it to oxaloacetate. In this way, the acetyl group enters the citric acid cycle for the final stages of oxidation.
GTP is formed in one step of the citric acid cycle. How is this GTP converted into ATP?
The high-energy phosphoryl group of the GTP is transferred to ADP to produce ATP. This reaction is catalyzed by the enzyme dinucleotide diphosphokinase.
What is the function of the intermembrane compartment of the mitochondria?
The intermembrane compartment is the location of the high energy proton (H+) reservoir produced by the electron transport system. The energy of this H+ reservoir is used to make ATP.
What is the major role of coenzyme A in catabolic reactions?
The major role of coenzyme A in catabolism is to carry the two-carbon acetyl group to the citric acid cycle. There the acetyl group is completely oxidized and large amounts of ATP are made.
Define the term mitochondrion
The mitochondrion is an organelle that serves as the cellular power plant. The reactions of the citric acid cycle, the electron transport system, and ATP synthase function together within the mitochondrion to harvest ATP energy for the cell.
How many molecules of ATP are produced when one molecule of NADH is oxidized by oxidative phosphorylation?
Three ATP
In what important way do the inner and outer mitochondrial membranes differ?
The outer mitochondrial membrane is freely permeable to substances of molar mass less than 10,000 g/mol. The inner mitochondrial membrane is highly impermeable. Embedded within the inner mitochondrial membrane are the electron carriers of the electron transport system, and ATP synthase, the multisubunit enzyme that makes ATP.
How many molecules of ATP are produced when one molecule of FADH2 is oxidized by oxidative phosphorylation?
The oxidation of FADH2 via oxidative phosphorylation yields 2 ATP.
What is the source of energy for the synthesis of ATP in mitochondria?
The oxidation of a variety of fuel molecules, including carbohydrates, the carbon skeletons of amino acids, and fatty acids provides the electrons. The energy of these electrons is used to produce an H1 reservoir. The energy of this proton reservoir is used for ATP synthesis
What is the purpose of the urea cycle?
The purpose of the urea cycle is to convert toxic ammonium ions to urea, which is excreted in the urine of land animals.
Which of the four allosteric enzymes or enzyme complexes in the citric acid cycle are under negative allosteric control? Which are under positive allosteric control?
The pyruvate dehydrogenase complex, the -ketoglutarate dehydrogenase complex, and citrate synthase are under negative allosteric control. Isocitrate dehydrogenase is under both positive and negative allosteric control.
Where do the reactions of the urea cycle occur?
The reactions of the urea cycle occur in the liver.
What is the role of coenzyme A in the reaction catalyzed by pyruvate dehydrogenase?
The role of coenzyme A in the reaction catalyzed by pyruvate dehydrogenase is to serve as a carrier of the two-carbon acetyl group that is produced by the oxidation and decarboxylation of pyruvate. The acetyl group is bonded to coenzyme A by a high-energy thioester bond; thus, acetyl-CoA is the "activated" form of the acetyl group.
What substances are the sources of each of the amino groups in the urea molecule?
The source of one amino group of urea is the ammonium ion, and the source of the other is the a-amino group of the amino acid aspartate.
In what form are the vitamins riboflavin, thiamine, niacin, and pantothenic acid needed by the pyruvate dehydrogenase complex?
The vitamin riboflavin is used to make the coenzyme FAD. Niacin is the precursor of the coenzyme NAD+. Pantothenic acid is a precursor for coenzyme A and thiamine is a precursor of thiamine pyrophosphate. All these coenzymes are required by the pyruvate dehydrogenase complex for the conversion of pyruvate to acetyl CoA.
In the oxidation of malate to oxaloacetate, what is the structural evidence that an oxidation reaction has occurred? What functional groups are involved?
This reaction is an example of the oxidation of a secondary alcohol to a ketone. The two functional groups are the hydroxyl group of the alcohol and the carbonyl group of the ketone.
Write a chemical equation for the production of acetyl CoA from pyruvate. Under what conditions does this reaction occur?
This reaction occurs under aerobic conditions.