Citric Acid Cycle Flashcards Preview

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Flashcards in Citric Acid Cycle Deck (20):
1

3 subunits of pyruvate dehydrogenase complex

E1 (pyruvate dehydrogenase with TPP coenzyme)
E2 (dihydrolipoamide acetyltransferase)
E3 (dihydrolipoamide dehydrogenase)

2

Pyruvate dehydrogenase mechanism

1. Decarboxylation of pyruvate
2. Transfer of hydroxyethyl group to lipoamide (E2 subunit)
3. Acetyl transfer to CoA
4. Reoxidation of lipoamide (E3 subunit's FAD is reduced to FADH2)
5. Reoxidation of FADH2 to FAD

3

Are the 2 carbons from acetyl CoA the 2 that are lost as CO2 in the citric acid cycle?

No- the 2 that are lost as CO2 come from oxaloacetate

4

Net reaction of the citric acid cycle

Acetyl CoA + 2 H2O + OH- + Pi + GDP -> 2 CO2 + HS-CoA + 7 H+ + 8 electrons (6 electrons from 3 NAD+ and 2 electrons from Q) + GTP
8 electrons -> 4 oxidations x 2 electrons/oxidation

5

Step 1 of citric acid cycle

Entry of substrate by condensation with oxaloacetate
Oxaloacetate + acetyl CoA -> Citrate + HS-CoA + H+
Enzyme: citrate synthase

6

How citrate synthase works

Citrate synthase has 2 domains: small and large
Oxaloacetate binding causes 20 degree rotation of small domain, creating acetyl CoA binding site (ensures that acetyl CoA isn't hydrolyzed without purpose)

7

Step 2 of citric acid cycle

Rearrangement
Citrate -> isocitrate
Enzyme: aconitase
Reason: tertiary alcohol can't be oxidized, but a secondary one can

8

Stereoselectivity of step 2

3 point attachment of substrate, citrate, to chiral enzyme, aconitase
2R, 3S-isocitrate is only isomer formed

9

Step 3 of citric acid cycle

First oxidative decarboxylation
Isocitrate + NAD+ -> alpha-ketoglutarate + NADH + CO2
Enzyme: isocitrate dehydrogenase
Secondary alcohol is oxidized to ketone

10

Step 4 of citric acid cycle

Alpha-ketoglutarate + HS-CoA + NAD+ -> succinyl CoA + CO2 + NADH
Enzyme: alpha-ketoglutarate dehydrogenase complex
Alpha-ketoacid is coupled to CoA with the loss of CO2 and the formation of a high-energy thioester

11

Step 5 of citric acid cycle

Succinyl CoA + GDP (or ATP) + Pi -> Succinate + GTP (or ATP) + HS-CoA
Enzyme: succinyl-CoA synthetase
Hydrolysis of high-energy thioester is coupled to formation of GTP or ATP (substrate level phosphorylation)

12

3 step mechanism of step 5

1. Thioester phosphorylysis
2. Phosphoryl transfer to enzymatic His residue
3. Phosphoryl transfer to GDP or ADP

13

Step 6 of citric acid cycle

Succinate + Q -> Fumarate + QH2
Enzyme: succinate dehydrogenase complex
Oxidation of alkane to trans-alkene, loss of 2 H+ and 2 electrons

14

Step 7 of citric acid cycle

Fumarate + H2O -> L-malate
Enzyme: Fumarase
Trans-addition of water to fumarate

15

Step 8 of citric acid cycle

L-malate + NAD+ -> oxaloacetate + NADH + H+
Enzyme: malate dehydrogenase
Secondary alcohol is oxidized to a ketone

16

ATP generated per NADH

2.5

17

ATP generated per QH2

1.5

18

ATP per acetyl CoA

10 (3 NADH x 2.5 ATP/NADH + 1 GTP or ATP + 1 QH2 x 1.5 ATP/QH2)

19

ATP per glucose

32 (Glucose -> 2 pyruvate: 2 NADH -> 5 ATP, 2 ATP; 2 pyruvate -> 2 acetyl CoA: 2 NADH -> 5 ATP; citric acid cycle: 6 NADH -> 15 ATP, 2 QH2 -> 3 ATP, 2 ATP)

20

Key points of regulation for citric acid cycle

1. Pyruvate dehydrogenase complex
2. Citrate synthase
3. Isocitrate dehydrogenase
4. Alpha-ketoglutarate dehydrogenase complex