Krebs TCA cycle

8 step Krebs cycle intermediates, enzymes, and products.

Step 1

Acetyl-CoA + Oxaloacetate ---> Citrate. Enzyme: Citrate Synthase. Importance: Irreversible entry step. Combines 2-carbon Acetyl-CoA with 4-carbon Oxaloacetate to form 6-carbon Citrate. Inhibited by ATP, NADH, and succinyl-CoA.

Step 2

Citrate ---> Isocitrate. Enzyme: Aconitase. Importance: Isomerization step that relocates the hydroxyl group to prepare the molecule for upcoming decarboxylation.

Step 3

Isocitrate ---> alpha-Ketoglutarate. Enzyme: Isocitrate Dehydrogenase. Cofactor: NAD+ -> NADH + CO2. Importance: Rate-limiting & irreversible step. First oxidation and carbon-loss step, producing NADH and releasing CO2. Activated by ADP/NAD+; inhibited by ATP/NADH.

Step 4

alpha-Ketoglutarate ---> Succinyl-CoA. Enzyme: alpha-Ketoglutarate Dehydrogenase Complex. Cofactor: NAD+ + CoA -> NADH + CO2. Importance: Irreversible oxidation step. Second carbon-loss step, producing NADH, releasing CO2, and attaching high-energy CoA. Inhibited by ATP, NADH, and succinyl-CoA.

Step 5

Succinyl-CoA ---> Succinate. Enzyme: Succinyl-CoA Synthetase. Cofactor: GDP + Pi -> GTP + CoA. Importance: Substrate-level phosphorylation step. Cleavage of the thioester bond drives GTP synthesis (which readily converts to ATP).

Step 6

Succinate ---> Fumarate. Enzyme: Succinate Dehydrogenase (Complex II of ETC). Cofactor: FAD -> FADH2. Importance: Membrane-bound step. Directly linked to the inner mitochondrial membrane, oxidizing succinate and reducing FAD to FADH2.

Step 7

Fumarate ---> L-Malate. Enzyme: Fumarase. Cofactor: Uses H2O. Importance: Hydration step that adds water across the double bond of fumarate to prepare for the final oxidation.

Step 8

L-Malate ---> Oxaloacetate. Enzyme: Malate Dehydrogenase. Cofactor: NAD+ -> NADH. Importance: Final oxidation step. Generates the third NADH of the cycle and regenerates Oxaloacetate to restart the cycle.

Products

1 ATP, 3 NADH, 1 FADH₂, 2CO₂