Citric Acid Cycle Enzymes - Biochemistry

Citrate synthase is the first enzyme of the citric acid cycle. Its role is to condense acetyl-CoA onto oxaloacetate in order to generate citrate.

Acetyl-CoA carboxylase is an enzyme that attaches a carboxyl group to acetyl-CoA in order to generate malonyl-CoA, which plays a role in fatty acid synthesis by contributing two carbons at a time to the growing hydrocarbon chain. Moreover, malonyl-CoA also serves a regulatory role in the breakdown and synthesis of fatty acids. Since it is a major precursor to the synthesis of fatty acids, high levels of it inhibit the breakdown of fatty acids by preventing fatty acids from entering the mitochondria, where they are broken down via beta-oxidation. Thus, malonyl-CoA allows fatty acids to be synethesized without simultaneously being degraded.

Thiolase is an enzyme that condenses two molecules of acetyl-CoA into acetoacetyl-CoA. This molecule is an important intermediate in two important pathways. One is the production of ketone bodies, while the other is the mevalonate pathway, which is an important series of reactions that synthesizes many compounds, such as cholesterol.

Pyruvate dehydrogenase is an enzyme complex that converts pyruvate into acetyl-CoA, thus linking glycolysis with the citric acid cycle.

Pyruvate carboxylase is an enzyme that adds a carboxyl group to pyruvate in order to generate oxaloacetate. This reaction can be used either to generate oxaloacetate for use in the kreb's cycle, or in the gluconeogenesis pathway to synthesize glucose from a variety of substrates.

The first step of the citric acid cycle involves the combination of acetyl-CoA with oxaloacetate, producing citrate. Next, aconitase catalyzes the isomerization of citrate to isocitrate, via the intermediate known as cis-aconitate. The conversion of isocitrate to alpha-ketoglutarate is catalyzed by isocitrate dehydrogenase. The citric acid cycle involves the conversion of fumarate to malate, not the reverse, although some bacteria do the reverse citric acid cycle to produce complex organic compounds. Succinyl-CoA is converted to succinate via succinyl-CoA synthetase (also known as succinate thiokinase).

Succinate dehydrogenase (also known as succinate-coenzyme Q reductase or complex II) is bound to the inner mitochondrial membrane. It participates in both the citric acid cycle and the electron transport chain. Aconitase is an enzyme involved in glycolysis, not the citric acid cycle (Krebs cycle).

All enzymes that have NADH as a product would be inhibited by the addition of NADH. The correct answers are citrate synthase, isocitrate dehydrogenase, and alpha-ketoglutarate dehydrogenase. Pyruvate dehydrogenase, which synthesizes acetyl-CoA from pyruvate, is also inhibited by NADH.

Each enzyme listed in the answer choices catalyzes a reaction in glycolysis or the citric acid cycle, but pyruvate dehydrogenase is the only one responsible for converting pyruvate to acetyl-CoA. Pyruvate is decarboxylated (removal of a ) and this is replaced with an S-CoA group, forming the necessary acetyl-CoA molecule to feed into the citric acid cycle.

Succinate dehydrogenase is the only enzyme in the citric acid cycle to use . The other dehydrogenases use while citrate synthase performs an unrelated reaction using acetyl-CoA.

Malate dehydrogenase catalyzes the conversion of malate to oxaloacetate and vice versa, while the other enzymes are the three irreversible steps in the citric acid cycle.

Succinate dehydrogenase catalyzes the reaction from succinate to fumarate. A byproduct of this reaction is the formation of from .

The only enzyme listed in the answer choices that does not catalyze a reaction within the citric acid cycle is pyruvate kinase. Pyruvate kinase is an important enzyme in the final step of glycolysis, as it catalyzes the conversion of phosphoenolpyruvate and ADP to pyruvate and ATP. This reaction is not contained within the citric acid cycle though, and therefore pyruvate kinase does not catalyze any reactions in the citric acid cycle.

Each of the other enzymes listed catalyzes reactions within the citric acid cycle, as follows:

Isocitrate dehydrogenase catalyzes the conversion of isocitrate to alpha-ketoglutarate.

Alpha-ketoglutarate dehydrogenase catalyzes the conversion of alpha-ketoglutarate to succinyl-CoA.

Succinyl-CoA synthetase catalyzes the conversion of succinyl-CoA to succinate.

Fumarase catalyzes the conversion of fumarate to malate.

The only enzyme listed in the answer choices that catalyzes a reaction within the citric acid cycle is isocitrate dehydrogenase, as it catalyzes the formation of alpha-ketoglutarate, carbon dioxide, NADH, and a proton, from isocitrate and .

Each of the other enzymes listed do not catalyze reactions within the citric acid cycle, but rather they catalyze reactions within glycolysis, as follows:

Pyruvate kinase catalyzes the conversion of phosphoenolpyruvate and ADP to pyruvate and ATP.

Glyceraldehyde-3-phosphate dehydrogenase catalyzes the conversion of glyceraldehyde-3-phosphate, , and inorganic phosphate to 1,3-bisphosphoglycerate, NADH, and a proton.

Phosphoglycerate kinase catalyzes the conversion of 1,3-bisphosphoglycerate and ADP to 3-phosphoglycerate and ATP.

Enolase catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate.

The only enzyme listed that participates in the citric acid cycle and catalyzes a step producing is succinate dehydrogenase. Succinate dehydrogenase catalyzes the conversion of succinate and FAD to fumarate and .

Pyruvate kinase is incorrect as it neither participates in the citric acid cycle (it is part of glycolysis), nor catalyzes a reaction that produces .

Isocitrate dehydrogenase catalyzes the conversion of isocitrate and to alpha-ketoglutarate, NADH, , and CO2, but not .

Fumarase catalyzes the conversion of fumarate and to malate, but not .

Aconitase catalyzes the conversion of cis-aconitate and to isocitrate, but not .

The citric acid cycle enzyme that catalyzes the reaction directly responsible for the production of succinyl-CoA is alpha-ketoglutarate dehydrogenase. Alpha-ketoglutarate dehydrogenase catalyzes the conversion of alpha-ketoglutarate, , and CoA-SH to succinyl-CoA, NADH, , and .

Each of the other enzymes listed are enzymes that participate in the citric acid cycle, but not in the step the directly produces succinyl-CoA. Their general roles are as follows:

Succinyl-CoA synthetase catalyzes the conversion of succinyl-CoA to succinate.

Succinate dehydrogenase catalyzes the conversion of succinate to fumarate.

Isocitrate dehydrogenase catalyzes the conversion of isocitrate to alpha-ketoglutarate.

Fumarase catalyzes the conversion of fumarate to malate.

The only correct statement within the answer choices is that succinyl-CoA synthetase catalyzes the reaction responsible for the formation of succinate. In this reaction, the citric acid cycle enzyme, succinyl-CoA synthetase, catalyzes the conversion of succinyl-CoA, GDP (or ADP) and inorganic phosphate to succinate, CoA-SH, and GTP (or ATP).

The incorrect answer choices are explained below:

"Succinyl-CoA synthetase is produced by the reaction catalyzed by alpha-ketoglutarate dehydrogenase."

This is incorrect because it is succinyl-CoA that is produced by the reaction catalyzed by alpha-ketoglutarate dehydrogenase. Succinyl-CoA synthetase, the enzyme, is not produced by this reaction.

"Succinyl-CoA synthetase catalyzes the reaction responsible for the rate-limiting step of glycolysis."

Succinyl-CoA synthetase does not participate in glycolysis; it participates in the citric acid cycle. Furthermore, even in the citric acid cycle, it does not catalyze the reaction responsible for the rate-limiting step of the citric acid cycle.

"Succinyl-CoA synthetase catalyzes the reaction responsible for the formation of succinyl-CoA."

Alpha-ketoglutarate dehydrogenase catalyzes the reaction responsible for the formation of succinyl-CoA. Succinyl-CoA synthetase catalyzes the reaction responsible for the conversion of succinyl-CoA to succinate.

"Succinyl-CoA synthetase directly catalyzes a citric acid cycle reaction that produces ."

Succinate dehydrogenase directly catalyzes a citric acid cycle reaction that produces , not succinyl-CoA synthetase.

The rate-limiting step of the citric acid cycle is catalyzed by the enzyme, isocitrate dehydrogenase. Isocitrate dehydrogenase catalyzes the conversion of isocitrate and to alpha-ketoglutarate, NADH, a proton, and a molecule of carbon dioxide.

Phosphofructokinase-1 (PFK-1) is incorrect, as it catalyzes the rate-limiting step of glycolysis, not the citric acid cycle.

Fructose 1,6-bisphosphatase is incorrect, as it catalyzes the rate-limiting step of gluconeogenesis, not the citric acid cycle.

Succinyl-CoA synthetase is incorrect, as it catalyzes a reaction within the citric acid cycle that is not the rate-limiting step.

Pyruvate kinase is incorrect as the reaction that it catalyzes is neither within the citric acid cycle, nor a rate-limiting step.

Aconitase is the enzyme that catalyzes the conversion of citrate to isocitrate. This essential enzyme is vital in energy production, as it acts like an iron regulatory protein. The conversion of citrate to isocitrate is important since it is needed to react with isocitrate dehydrogenase.

Citrate synthase is the first enzyme of the citric acid cycle. Its role is to condense acetyl-CoA onto oxaloacetate in order to generate citrate.

Acetyl-CoA carboxylase is an enzyme that attaches a carboxyl group to acetyl-CoA in order to generate malonyl-CoA, which plays a role in fatty acid synthesis by contributing two carbons at a time to the growing hydrocarbon chain. Moreover, malonyl-CoA also serves a regulatory role in the breakdown and synthesis of fatty acids. Since it is a major precursor to the synthesis of fatty acids, high levels of it inhibit the breakdown of fatty acids by preventing fatty acids from entering the mitochondria, where they are broken down via beta-oxidation. Thus, malonyl-CoA allows fatty acids to be synethesized without simultaneously being degraded.

Thiolase is an enzyme that condenses two molecules of acetyl-CoA into acetoacetyl-CoA. This molecule is an important intermediate in two important pathways. One is the production of ketone bodies, while the other is the mevalonate pathway, which is an important series of reactions that synthesizes many compounds, such as cholesterol.

Pyruvate dehydrogenase is an enzyme complex that converts pyruvate into acetyl-CoA, thus linking glycolysis with the citric acid cycle.

Pyruvate carboxylase is an enzyme that adds a carboxyl group to pyruvate in order to generate oxaloacetate. This reaction can be used either to generate oxaloacetate for use in the kreb's cycle, or in the gluconeogenesis pathway to synthesize glucose from a variety of substrates.

The first step of the citric acid cycle involves the combination of acetyl-CoA with oxaloacetate, producing citrate. Next, aconitase catalyzes the isomerization of citrate to isocitrate, via the intermediate known as cis-aconitate. The conversion of isocitrate to alpha-ketoglutarate is catalyzed by isocitrate dehydrogenase. The citric acid cycle involves the conversion of fumarate to malate, not the reverse, although some bacteria do the reverse citric acid cycle to produce complex organic compounds. Succinyl-CoA is converted to succinate via succinyl-CoA synthetase (also known as succinate thiokinase).

Succinate dehydrogenase (also known as succinate-coenzyme Q reductase or complex II) is bound to the inner mitochondrial membrane. It participates in both the citric acid cycle and the electron transport chain. Aconitase is an enzyme involved in glycolysis, not the citric acid cycle (Krebs cycle).

All enzymes that have NADH as a product would be inhibited by the addition of NADH. The correct answers are citrate synthase, isocitrate dehydrogenase, and alpha-ketoglutarate dehydrogenase. Pyruvate dehydrogenase, which synthesizes acetyl-CoA from pyruvate, is also inhibited by NADH.