4 - The Citric Acid Cycle and How it Functions Under Aerobic Conditions

What are the reactants of the first step of the Citric Acid Cycle?

Acetyl-CoA and oxaloacetate

What is the product of the first step of the Citric Acid Cycle?

Citrate and Coenzyme A (CoA-SH)

What enzyme catalyzes the first step of the TCA cycle?

Citrate Synthase

What type of reaction is catalyzed by citrate synthase in the first step?

A lyase reaction and an aldol condensation

Is the first step of the TCA cycle reversible?

No, the reaction is irreversible

What is the substrate/reactant of the last step of the TCA cycle?

Malate

What is the product of the last step of the Citric Acid Cycle?

Oxaloacetate

What enzyme catalyzes the last step of the TCA cycle?

Malate Dehydrogenase

What coenzyme is reduced in the last step of the cycle?

NAD⁺ is reduced to NADH

Is the last step of the TCA cycle reversible?

Yes, but the reaction is pulled forward by constant removal of oxaloacetate for the citrate synthase reaction

How does the TCA cycle support energy generation under aerobic conditions?

By producing NADH and FADH₂, which donate high-energy electrons to the electron transport chain (ETC) to drive ATP synthesis via oxidative phosphorylation

How many molecules of NADH are generated per turn of the TCA cycle?

Three NADH molecules

At which steps of the TCA cycle is NADH generated?

• Isocitrate → α-Ketoglutarate (Isocitrate Dehydrogenase)

• α-Ketoglutarate → Succinyl-CoA (α-Ketoglutarate Dehydrogenase)

• Malate → Oxaloacetate (Malate Dehydrogenase)

How many FADH₂ molecules are generated per TCA cycle turn?

One FADH₂

At which step of the TCA cycle is FADH₂ generated?

Succinate → Fumarate, catalyzed by Succinate Dehydrogenase.

Why are NADH and FADH₂ important in aerobic metabolism?

They carry high-energy electrons to the ETC, where they drive proton pumping and ATP synthesis via oxidative phosphorylation.

What reaction occurs between acetyl-CoA and oxaloacetate, and which enzyme catalyzes it?

Claisen condensation (lyase + aldol-type) reaction forming citrate, catalyzed by Citrate Synthase

Step 2: What type of reaction converts citrate to isocitrate, and what enzyme catalyzes it?

Isomerization (dehydration followed by rehydration) catalyzed by Aconitase via the intermediate cis-aconitate

Step 3: What type of reaction is catalyzed by Isocitrate Dehydrogenase?

Oxidative decarboxylation (oxidation of alcohol to ketone, then β-decarboxylation), forming α-ketoglutarate and CO₂, and producing NADH

What type of reaction is catalyzed by the α-Ketoglutarate Dehydrogenase Complex?

Another oxidative decarboxylation, similar to PDC: cleavage of α-keto acid, producing succinyl-CoA, CO₂, and NADH

Step 5: What is the reaction type and enzyme that converts succinyl-CoA to succinate?

Substrate-level phosphorylation, catalyzed by Succinyl-CoA Synthetase (Succinate Thiokinase); GTP (or ATP) is formed

Step 6: What kind of reaction is catalyzed by Succinate Dehydrogenase?

Oxidation, converting succinate to fumarate while reducing FAD to FADH₂

Step 7: What type of reaction converts fumarate to malate, and which enzyme is responsible?

Hydration of a double bond, catalyzed by Fumarase (Fumarate Hydratase)

Step 8: What type of reaction is catalyzed by Malate Dehydrogenase?

Oxidation of a secondary alcohol to a ketone, forming oxaloacetate and reducing NAD⁺ to NADH