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Citric Acid Cycle 1
C483 Spring 2013
1. The net effect of the eight steps of the citric acid cycle is to
A) completely oxidize an acetyl group to carbon dioxide.
B) convert pyruvate to Acetyl CoA.
C) produce a citrate molecule
D) produce 8 ATP for every pass through the cycle.
E) More than one of the above
2. The order of prosthetic groups as they act in the three proteins of the
PDH(pyruvate dehydrogenase) complex is:
A) FAD → thiamine pyrophosphate → NAD+
B) FAD → thiamine pyrophosphate → dihydrolipoamide
C) thiamine pyrophosphate → dihydrolipoamide → FAD
D) NAD+ → FAD → dihydrolipoamide
3. Which might you expect to have a higher than normal blood concentration in
an individual with thiamine deficiency?
A) Isocitrate.
B) Pyruvate.
C) Oxaloacetate.
D) Acetyl CoA.
4. About how many total ATP equivalents are generated by the complete
oxidation of one molecule of acetyl CoA?
A) 1.5
B) 2.5
C) 3
D) 10
E) 30
5. Which product of the citric acid cycle produces the most ATP equivalents?
A) NADH.
B) QH2.
C) GTP.
D) CO2.
Overview
• Compartmentalization
– Glycolysis: Cytosol
– Citric Acid Cycle: mitochondria
Overview
• Glycolysis
• Pyruvate dehydrogenase
complex
– Commitment of carbon away
from carbohydrates
• Citric acid cycle
Pyruvate Dehydrogenase Complex
• Three distinct enzymes—in a massive complex
• Five chemical steps
• What cofactors needed?
Pyruvate Dehydrogenase (E1)
• TPP cofactor: draw mechanism of
decarboxylation
Dihydrolipoamide Acyltransferase (E2)
• Transfer catalyzed by E1
• Mechanism of redox
Step 3: transfer
• Maintenance of high energy bond
• Acetyl CoA product is made
• Lipoamide still reduced—not catalytically
viable at this point
Dihydrolipoamide dehydrogenase (E3)
• Redox of prosthetic FAD/FADH2
• Still not a regenerated catalyst!
Step 5: NADH produced
• Prosthetic group is restored
• Step 1 uses proton, step 5 regenerates
• Oxidation of one carbon atom used to
– Produce high energy thioester
– Produce NADH
Overall Reaction
Fate of Acetyl CoA
• Citric Acid Cycle (in muscle)—energy
production (high potential electrons)
• Other tissues use intermediates in many ways
– Amphibolic
Citric Acid Cycle
• Major points: carbon cycle, reaction types,
reaction logic, energy harvest, selected
enzyme reactions
• Minor points: enzyme names, substrate
names, order of reactions
Energy Flow
• Decarboxylation or
alcohol oxidation =
NADH
• Double bond
formation = QH2
• Dehydrogenases
• High energy bond =
substrate
phosphorylation
ATP Harvest: Net equations
Net ATP Harvest from Glucose
• Glycolysis = 2 ATP
– Plus 3 or 5 ATP from
NADH
– In humans, cytosolic
NADH leads to
production of 3 ATP
• Pyruvate DH = 5 ATP
• Citric Acid Cycle = 20
ATP
• Total: 30 ATP/glucose
in humans
Answers
1.
2.
3.
4.
5.
A
C
B
D
A