The citric acid cycle (Krebs cycle)

Question 1

Albert Szent-Györgyi

Answer 1

found that several organic acid acted catalytically

Question 2

Hans Krebs

Answer 2

• discovered the citric acid cycle
• realized the metabolism of the reactions were linked in a cyclic pathway

Question 3

Step 1: Acetyl CoA + Oxaloacetate form citrate

Answer 3

• condensation reaction
• input of H2O and output of CoA
• enzyme: citrate synthase
• methyl of acetyl CoA acts as a nucleophile

Question 4

Step 2: Citrate to Isocitrate

Answer 4

• isomerization reaction
• forms intermediate cis-aconitate
• output then input of H2O
• enzyme: aconitase

Question 5

Step 3: Isocitrate to a-ketoglutarate

Answer 5

• oxidative decarboxylation
• NAD+ becomes NADH
• output of CO2
• enzyme: isocitrate dehydrigenase

Question 6

Step 4: a-ketoglutarate to Succinyl CoA

Answer 6

• oxidative decarboxylation
• input of CoA, output of CO2
• identical mechanism to pyruvate dehydrogenation complex
• NAD+ becomes NADH
• enzyme: a-ketoglutarate dehydrogenase
• high energy reaction

Question 7

Step 5: Succinyl CoA to succinate

Answer 7

• substrate level phosphorylation
• ADP to ATP
• releases CoA
• enzyme: succinylcholine CoA synthetase

Question 8

Step 6: succinate to fumarate

Answer 8

• oxidation
• FAD to FADH2
• analogous to acyl-CoA hydrates of B-oxidation
• enzyme: succinate dehydrogenase

Question 9

Step 7: fumarate to malate

Answer 9

• hydration (input H2O)
• analogous to enrol-CoA hydrates in B-oxidation
• enzyme: fumarase

Question 10

Step 8: Malate to oxaloacetate

Answer 10

• oxidation
• NAD+ to NADH
• analogous to hydroxyacyl CoA dehydrogenase from B-oxidation
• enzyme: malate dehydrogenase

Question 11

Net effect of TCA cycle

Answer 11

• two carbons from acetyl CoA are oxidized to CO2
• 3NAD+ and 1FAD are reduced to 3NADH and 1FADH2
• one ATP is formed per cycle

Question 12

why does citrate form cis-aconitate intermediate before it becomes isocitrate

Answer 12

• it is a tertiary alcohol (poor for oxidation)
• elimination of H2O gives cis C=C bond
• hydrolization of this bond gives a secondary alcohol (good for oxidation)

Question 13

reaction mechanism of succinyl-CoA

Answer 13

• Pi displaces CoA to form high energy acyl phosphate
• reactive his residue accepts phosphate, release succinate
• phosphate is transferred from phosphorylation enzyme to ATP, releasing the enzyme

Question 14

in an experiment with pigeon breast muscle, the addition of fumarate stimulated the removal of acetyl CoA with a 1:1 stoicheometric fashion. what does this say about the Krebs cycle?

Answer 14

the cycle is inhibited between succinate and furimate