Acetyl-CoA + Oxaloacetate -> Citrate
Enzyme: Citrate Synthase
first a reversible conversion to S-Citryl-CoA Intermediate, and then spontaneous irreversible conversion to Citrate
Citrate -> into?
Citrate -> Isocitrate
Enzyme = Aconitase
First a dehydration into Cis-aconitate Intermediate, then a rehydration into isocitrate
Isocitrate -> into?
Isocitrate -> Alpha-Ketoglutarate
Enzyme = Isocitrate Dehydrogenase
First an irreversible oxidation to Oxalosuccinate Intermediate (with NAD+ -> NADH & H+), then an irreversible decarboxylation (remove CO2) into alpha-ketoglutarate
Alpha-ketoglutarate -> into?
Alpha-ketoglutarate + HS-CoA + NAD+ -> Succinyl-CoA (+ NADH + CO2)
Enzyme: Alpha-ketoglutarate dehydrogenase complex
NAD+ reduces rxn -> NADH & H+, also decarboxylation occurs (CO2 removed)
- now structure has returned to 4 carbons, the rest of cycle just returns to oxaloacetate -
Succinyl-CoA -> into?
Succiny-CoA + Pi + GDP -> Succinate + GTP
Enzyme: Succinyl-CoA Synthetase
(example of coupled reaction: hydrolysis of one high E bond to form another)
(GTP can pass Pi to ADP -> ATP via NDP Kinase)
Succinate -> into?
Succinate + FAD -> Fumarate + FADH2
Enzyme: Succinate Dehydrogenase
Succinate dehydrogenase is also part of Electron Transport Chain! aka Complex II (only enzyme that particpates in both)
Fumarate -> into?
Fumarate + H2O -> Malate
Always L-Malate configuration is formed
Malate -> into?
Malate + NAD+ -> Oxaloacetate + NADH & H+
Enzyme: Malate Dehydrogenase
- Not spontaneous! Pushed forward by high [malate] : [oxaloacete] ratio
- Final step, back to oxaloacetate!
What are the steps that are irreversible?
(large neg delta G)
Step 1: Citrate synthase
Step 3: Isocitrate Dehydrogenase
Step 4: alpha-Ketoglutarate Dehydrogenase Complex