Chapter 17: The Citric Acid Cycle

It's a source of precursors for synthesis.

Chapter 17 begins with a detailed discussion of the reaction mechanisms of the pyruvate dehydrogenase complex, followed by a description of the reactions of the citric acid cycle.
There are details of mechanism and stereospecificity of some of the reactions in this description.
In the following sections, they describe the pathway including the energy yield and control mechanisms.
The chapter ends with a summary of the biosynthetic roles of the citric acid cycle and its relationship to the glyoxylate cycle found in plants.

Chapters 8 through 10, the introduction to metab olism, and the chapter on glycolysis contain essential background material for this chapter.

You should be able to complete the objectives when you have mastered this chapter.

The cycle is found in the cells.

The citric acid cycle has several enzymatic reactions.

There are logical roles of GTP.

The effects of heavy metal poisoning are compared.

List the reactions that are unique.

Match the cofactors of the pyruvate dehydrogenase complex in the left column with their corresponding enzyme components and with their roles in the enzymatic steps that are listed in the right column.

citryl CoA is formed by the hydrolyzing of the thioester bond of acetyl CoA and oxaloacetate.

Draw the structure of isocitrate and show the atoms in bold letters.

Each of them will be catalyzed by the enzyme.

The first few structures in the cycle are shown with the "new" acetate carbons at the bottom.

In CO2, the label will be lost.

The pyruvate dehy drogenase complex is activated by the pyruvate dehydrogenase component.

The citric acid cycle is regulated by the enzymes in the left column.

The appropriate control mechanisms are in the right column.

The functions of the citric acid cycle are performed by the glyoxylate cycle in plants andbacteria.

The biosynthetic products in mammals are listed in the right column.

The synthesis of certain amino acids requires the use of citric acid cycle intermediates.

The decarboxylation of oxaloacetate can be done with Pyruvate carboxylase.

The condensation of gly oxylate with acetyl CoA can be accomplished by Malate synthase.

A complex reaction can be carried out by a multienzyme complex.

The intermediates in the reaction remain bound to the complex and are passed from one component to the next, which increases the overall reaction rate and reduces side reactions.

The reaction intermediates would have to diffuse randomly.

After oxaloacetate has been bound, the en zyme structure has rearranged to create a binding site for acetyl CoA.

After citryl CoA is formed, there are structural changes that bring an aspartate and a water molecule into the vicinity of the thioester bond for the hydrolysis step.
acetyl CoA is protected.

The text doesn't go into detail about the stereochemistry of the aconitase, but it does say that the double bond and the hydroxyl on the side of the molecule are away from the "new" carbons introduced from Acetyl CoA.

The middle carbons of oxaloacetate will be labeled because they are symmetrical.

About 30 ATP are formed from glucose to CO2 and H2O.

The oxidation reduction reactions of the citric acid cycle are dependent on the cofactors NAD+ and FAD.

The cofactors are regenerated by transfer of electrons through the electron transport chain to O2 to give H2O.

The text points out that the inhibition of citrate synthase is species specific.

oxaloacetate and acetyl CoA are available in all organisms.

In the various dehydrogenation reactions of the citric acid cycle, NAD+ and FAD are absolutely required as electron acceptors.

The citric acid cycle stops when the cofactors are not available.

The condensation of glyoxylate and acetyl CoA is similar to the condensation of oxaloacetate and acetyl CoA in the citric acid cycle.

In order to prevent the premature hydrolysis of acetyl CoA, the initial binding of glyoxylate, which causes structural changes in the enzyme that allow the subsequent binding of acetyl CoA, would be expected.

You can see question 5.

The glyoxylate cycle can be used to synthesise four-carbon precursor mol ecules.

In the citric acid cycle, the carbon atoms from acetyl CoA are released as CO2, and there is no net synthesis of four-carbon molecule.

A single NADH can yield 2.5 million units of the molecule of the molecule of the molecule of the molecule of the molecule of the molecule of the molecule of the molecule of the molecule of the molecule of the molecule of the molecule of the molecule of the molecule of the molecule of the molecule of

The mechanism for the reaction is proposed.

When an isolated rat heart is perfused with sodium fluoroacetate, the rate of glycolysis decreases.

Oxaloacetate is used to give fluorocitrate in cardiac cells.

A dehydration-rehydration reaction with aconitate is what leads to the conversion of citrate to isocitrate in the citric acid cycle.

The conversion of citrate to aconitate and aconitate to isocitrate is done by a single enzyme.

There are two groups in the isocitrate dehydrogenase.

Discuss their possible roles in the reaction.

The conversion of succinate to malate is a potent activity of Malonate anion.

There is a pathway from citrate to succinct in animal tissues.

Krebs noticed that citrate enhances respiration in muscle tissues.
He knew that malonate reduces the rate of respiration in animal cells.
Fumarate was added to the malonate-poisoned muscle.

Studies show that oxaloacetate has an effect on succinate dehydrogenase activity.

As crushed grapes turn to wine, winemakers have to understand what is happening.

The major pathway is glycolysis.
As more CO2 is produced, it can lead to sparkling wine.
The L-lactate is produced bybacteria that bind L-malic acid and decarboxylate it to form L-lactate.
The wine is more complex and less acidic as a result of this process.
Initial experiments failed to produce malolactic fermentation using only yeast, but after some thought, researchers inserted another gene into the yeast and the process succeeded.

Oysters live their adult lives on the sea floor.

Sometimes the local environment can become a problem.

Oysters accumulate succinate when they are deprived of oxygen.

Even though the citric acid cycle can't be run as a cycle in the absence of oxygen, the reactions can be exploited in a way that maintains the redox balance.
The four-carbon reactions are run backwards.
NAD+ and FAD are reduced.
The cycle runs from the beginning to the end.
There are two NADH molecules produced by this.

The oxidation of acetate was proposed by Thunberg in the early 1900s.

In his scheme, two molecules of acetate are reduced to form a single molecule, which in turn is converted to oxaloacetate.
The decarboxylation of oxaloacetate to pyruvate is the last part of the cycle.
If electron carriers like FAD would be part of the scheme, compare the energy liberated by the scheme to the energy liberated by the citric acid cycle.

A cell is deficient.

It is important for muscles to have a source of energy.

Pyruvate dehydrogenasephosphate phosphatase is activated by calcium ion, which increases concentration during exercise.

The carboxylation of pyruvate is one of the anaplerotic reactions that help maintain appropriate levels of oxaloacetate.

The a-keto acids can be obtained by removing the respective groups of glutamate and aspartate.

The oxidation of a fatty acid with an even number of carbon atoms yields a number of acetyl CoA, whereas the oxidation of an odd number of carbon atoms yields propionyl CoA.

The sole carbon source for some organisms is ethanol.

If you propose a pathway for the utilization of this two-carbon compound, you should convert it into one or more molecules that can be used for energy generation and as biosynthetic precursors.

Most of the energy is provided by the citric acid cycle.

It is how we make a living.
There are biochemical strategies that are unrelated.

The sequence for converting methane into CO2 should be proposed.

The mechanism is similar to the one shown on page 469 of the text, in which the C-2 car banion of TPP attacks the a-keto group of pyruvate.

The decarboxylation of pyruvate is enhanced by the delocalization of electrons.

The initial product is cleaved to yield acetaldehyde andTPP.

In contrast to the reaction catalyzed by pyruvate dehydrogenase, there is no net oxidation.

The decrease in the levels of other citric acid cycle in termediates suggests that aconitase is prevented by fluorocitrate.

Excess citrate causes a decrease in the rate of glycolysis and an increase in the number of monophosphates.

Environmentalists and farmers and ranchers are at odds over whether or not to use Compound 1080 outdoors.

There is no antidote because it acts on cells in a way that causes a slow and painful death.

It is a tertiary alcohol, which is difficult to oxidize, and has an alcohol function.

Isomerization of citrate to isocitrate makes it easier to decarboxylate.

The sum of the two values for individual reactions is the standard free-energy value for the conversion of citrate to isocitrate.

Everything would be present at 1 molar concentration under standard conditions.

The reaction toward net formation of that molecule would be pulled by this lower concentration of isocitrate.

Increased concentrations of citrate could cause the formation of isocitrate once more.

It appears that both mechanisms may operate to ensure net isocitrate synthesis.

The acceptor for electrons from isocitrate is contained in Lipoic acid.

FAD could transfer those electrons to NAD+.
The roles of the groups are similar to those they play in the reaction.

Malonate is unreactive because it has only one methylene group.

We now know that fumarate can be seen as a component of the citric acid cycle.

A block in the conversion of succinate to fumarate would cause an increase in concentration.
In the first experiment, the pathway from citrate to succinate was shown to be significant and related to the process of respiration.
The second experiment suggested that there is a separate pathway from fumarate to succinate.
Krebs realized that there was a pathway that could account for all of the observations.
The piece of the puzzle that was left was to find out how pyruvate or acetate could be used to make citrate.
The results of those experiments are described.

He was able to use the results of his experiments and others to show how a cyclic pathway could function to carry out oxidation of carbon molecule while regenerating oxaloacetate.

The ornithine cycle, which is used for urea synthesis, was shown to be a cyclic pathway by Krebs.

Succinct dehydroge nase, fumarase, and malate dehydrogenase are involved in the creation of oxaloacetate.

One would expect the activity of oxaloacetate to be reduced when it is high.
Succinct production would be increased if there were low levels of oxaloacetate.

Lactic acid has one.

As malate is converted into lactate and carbon dioxide, the wine's pH changes.

The researchers were able to insert a gene for malate permease, which would allow malate to enter the yeast cells.

The system started working well with both genes.

GTP is created by one high-energy bond.

While the NADH used up cancels out the NADH produced, we have a second NADH that can provide electrons through the electron transport chain to reduce FAD.

The passage of a pair of electrons forward through Complex I and backward through Complex II should produce enough of a proton gradient to form another ATP.
The basic facts of the production of ATP in the mitochondria are described in Section 17.1.9 of the text, but the details of the production will be discussed in Chapter 18.

3 NADH and 1 FADH2 are generated for each group consumed, and their reoxidation in the electron transport chain provides energy for the generation of nine molecules of ATP.

The energy liberated by both schemes is the same because pyruvate dehydrogenase and the citric acid cycle have the same action.
The condensation of two acetyl groups to form succinate is one of the reactions shown in the scheme.

The rate of synthesis of acetyl CoA can be accelerated by removing a phosphoryl group from pyru vate dehydrogenase.

The rate of entry of acetyl groups into the citric acid cycle will decrease if cells deficient in phosphatase activity are not activated.
As the cell responds to a continued requirement for ATP synthesis, stimulation of glycolytic activity and an increase in lactate production would be expected.
The clinical note can be found on page 481 of the text.

The phosphatase stimulates the rate of both glycolysis and the citric acid cycle.

Increased production of ATP is available for muscle contraction when pyruvate dehydrogenase is activated.

The structures of the a-keto acid analogs of glutamate and aspartate are in fact both citric acid cycle intermediates, a-ketoglutarate and oxaloacetate.

When deaminated, aspartate contributes directly to the addition of oxaloacetate.

oxaloacetate is a component of the citric acid cycle.

The net synthesis of oxaloacetate is not affected by the entry of acetyl groups into the citric acid cycle.

The relative number of carbon atoms in the pathway can only be increased by compounds with three or more carbons.
The compounds with an even number of fatty acids do not contribute to the net synthesis of oxaloacetate.

The microorganism first converts acetic acid to acetic acid by carrying out two successive oxidations.

A reduced electron carrier will be produced.
The acetyl group is transferred to oxaloacetate to form citrate after the action of acetyl CoA.
The net formation of oxaloacetate from isocitrate and another molecule of acetyl CoA is assisted by two enzymes from the glyoxylate cycle.
Oxaloacetate can be used in the production of biosynthetic intermediates.
It is necessary for a small amount of oxaloacetate and other intermediates of the citric acid cycle to be present in order for acetate to enter the pathway.

Methane is first converted to methanol by a monooxygenase and then to water by a reductant.

The electron acceptor in this step is a novel quinone.

Formaldehyde is converted to CO2 by formic acid.

The two steps contain NADH.
There are 2.5 and 1.5 from NADH.

Figure 17.15 shows carbon atoms around the citric acid cycle to answer the problem.

This problem assumes that all pyruvate goes to acetyl CoA.
Since pyruvate can enter the cycle at oxaloacetate, this is not necessarily true.

CHAPTER 17 (c) is about the formation of acetyl CoA from pyruvate.

They can't carry out the gly oxylate cycle because they don't have these two enzymes.

The small-molecule intermediates in the citric acid cycle are not eaten.

The cycle intermediates are regenerated at a particular point during each turn of the cycle.
The release of free coenzyme A and the production of GTP, FADH2, and three molecules of NADH is a part of the cycle as a whole.

The stereospecificity of glyceraldehyde 3-phosphate dehydrogenase is different from that of alcohol dehydrogenase.

It is a transition state analog.

The transition state of the normal coenzyme in thiamine-catalyzed reactions is similar to that of the sulfur-containing ring of this analog.

The citric acid cycle cannot operate in a sustained manner without O2 as a terminal acceptor.

The pyruvate that is produced by glycolysis must be reduced so that the NADH produced in the process can be converted to NAD+.
The production of CO2 and acetyl-CoA is a product of the pyruvate dehydrogenase complexample.

The reaction is pushed uphill because of the differences in concentration.

The smallest [Mal]/[OAA] ratio permitting net OAA formation is 1.75 x 104.

Pi 2 NADH + 3H+ 10 The only way to get the carbons from fats into oxaloacetate is through the citric acid cycle.

Although two carbon atoms enter the cycle as acetyl CoA, two carbon atoms are lost as CO2 before oxaloacetate is formed.

A C-C bond can be formed by the enolate anion of acetyl CoA.

This reaction is similar to the condensation of oxaloacetate.
The reactions are nearly identical despite the fact that glyoxylate has a hydrogen atom.

The carbons in the drawing are from acetyl-CoA.

Carbon 6 is lost in the formation of a-ketoglutarate, so the label from carbon 5 is not lost in that step.

The upper H on the small molecule can never be binding to groups X, Y, and H'.

The two hydrogens on the carbon atom are distinguishable by their relative orientations.

4.5 O2 4 H2O + 6 CO2 from the balanced equation would be consumed per mole of citrate.

The result could suggest that the citrate is being regenerated in a cycle, rather than being consumed.

The regeneration of the citrate is blocked at low concentrations, so it disappears almost completely.

Some steps between the block and the citrate may reversibly approach equilibrium, but not all of it.

The number of cfu is restored when the isocitrate lyase gene is restored.

Without the gly synthesisoxalate cycle, it's not possible to have Carbohydrates from lipids.

There is a chance that the glyoxalate cycle will be missing.