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 enzymesin 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 reducednot 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