10.3 Citric Acid Cycle Flashcards
Which steps are irreversible in the CAC?
1,3,4
Reaction 0
Substrate: pyruvate, NAD+, CoA
Product: acetyl-CoA, NADH, CO2
Enzyme: pyruvate dehydrogenase complex (E1, E2, and E3)
CAC Net reaction
Acetyl-CoA + 3 NAD+ + FAD + GDP + Pi + 2 H2O → CoA + 2 CO2 + 3 NADH + 3 H+ + FADH2 + GTP
Reaction 1
Substrates: acetyl-CoA, oxaloacetate, H2O
Products: citrate, CoA
Enzyme: citrate synthase
Irreversible
Citrate synthase
ordered mechanism: Oxaloacetate binds first, then a conformational change allows Acetyl CoA to bind
Reaction 2
Substrate: citrate
Product: isocitrate
Enzyme: aconitase
involves cis-aconitate intermediate
Enzyme inhibition: fluoroacetate
Fluorocitrate inhibits aconitase
* Used as rat poison
* Blocks citrate export
Reaction 3
Substrates: isocitrate, NAD+
Products: α-ketoglutarate, NADH, CO2
Enzyme: isocitrate dehydrogenase
IRREVERSIBLE
Reaction 4
Substrates: α-ketoglutarate, NAD+, CoA-SH
Products: succinyl-CoA, NADH + H+, CO2
Enzyme: α-ketoglutarate dehydrogenase
IRREVERSIBLE, Same mechanism as pyruvate dehydrogenase
Reaction 5
Substrates: succinyl-CoA, Pi, GDP
Products: succinate, CoA, GTP
Enzyme: succinyl-CoA synthetase
Reaction 6
Substrates: succinate, FAD (Q)
Products: fumarate, FADH2 (QH2)
Enzyme: succinate dehydrogenase
FAD prosthetic group serves as electron transport intermediate
Reactions happens near IMM
Linked to electron transport system
Reaction 7
Substrates: fumarate, H2O
Product: malate
Enzyme: fumarase
Carbanion intermediate
Hydrates C=C double bond
Fumarase highly stereo-specific, generates L-malate only
Reaction 8
Substrates: malate, NAD+
Products: oxaloacetate, NADH, H+
Enzyme: malate dehydrogenase
Coupled to reaction 1; common intermediate; step one pushes step 8 forward
Where is NADH produced?
Steps 3,4,8
Where is FADH2 produced?
Step 6