The TCA [Citric Acid / Krebs] Cycle [detailed]

The Citric Acid Cycle

• Takes place in the mitochondrial matrix. For each molecule of glucose, this cycle happens two times.
• For a single turn, it produces:
• 1 ATP
• 3 NADH
• 1 FADH2
• 2 CO2 (byproduct, two released per every one acetyl group that passes through the cycle).
• NADH and FADH2 are used to store energy.
• The citric acid cycle's primary goal is to reduce electron carriers like NAD+ and FAD.
• The reduced forms, NADH and FADH2 donate their electrons to the electron transport chain.
• These products will then be used in the Electron Transport Chain (ETC) to generate more ATP.

Reaction #1: Acetyl CoA + oxaloacetate + H2O → Citrate + CoA

• Condensation reaction (uses water).
• Catalyzed by citrate synthase.
• Acetyl transferred to oxaloacetate (OAA), plus water, to form citrate.

Reaction #2: Citrate → Isocitrate

• Catalyzed by aconitase.
• Transfers hydroxyl group from central carbon to the carbon beside it.

Reaction #3: Isocitrate + NAD+ → α-ketoglutarate + NADH + H+ + CO2

• Decarboxylation and oxidation.
• Catalyzed by isocitrate dehydrogenase.
• CO2 released by decarboxylation reaction, resulting in free energy loss that is harnessed as NADH.

Reaction #4: α-Ketoglutarate + NAD+ + CoA → Succinyl CoA + NADH + H+ + CO2

• Decarboxylation and oxidation.
• Catalyzed by α-Ketoglutarate dehydrogenase complex.
• Releases CO2 (free energy harnessed as NADH) and produces a high energy compound called succinyl CoA.

Reaction #5: Succinyl CoA + GDP + Pi → Succinate + GTP + CoA-SH

• Phosphorylation reaction.
• Catalyzed by succinyl CoA synthetase.
• Energy is transferred from high energy bonds in succinyl CoA to GDP, producing GTP.
• Succinate is produced in the process and the CoA group is removed.

Reaction #6: Succinate + FAD → FADH2 + Fumarate

• Oxidation reaction.
• Catalyzed by succinate dehydrogenase.
• Electrons and hydrogens removed and transferred form succinate to FAD (Q = FAD) to produce FADH2.

Reaction #7: Fumarate + H2O → Malate

• Condensation reaction.
• Catalyzed by fumarase.
• Hydroxyl group added to one of the carbons of fumarate.

Reaction #8: Malate + NAD+ → Oxaloacetate + NADH + H+

• Oxidation reaction.
• Catalyzed by malate dehydrogenase.
• Hydroxyl (OH) group is oxidized, generating a carbonyl group. The electrons and hydrogens are transferred to NAD+ to form NADH + H+.

Summary of the citric acid cycle

1. 2C's enter in acetyl-CoA and 2C's leave as CO2.
2. 4 reduced electron carriers are generated: 3NADH and FADH2.
3. High energy GTP is formed.
4. Cycle happens in only one direction.
5. Cycle depends on oxygen. NADH and FADH2 donate electrons to oxygen to regenerate NAD+ and FAD.

Net reaction: Acetyl-CoA + 3NAD+ + FAD + GDP + Pi → 2CO2 + CoA + 3NADH + FADH2 + GTP