Citric Acid Cycle 1

C483 Spring 2013

1. The net effect of the eight steps of the citric acid cycle is toA) completely oxidize an acetyl group to carbon dioxide.B) convert pyruvate to Acetyl CoA.C) produce a citrate moleculeD) 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 → dihydrolipoamideC) thiamine pyrophosphate → dihydrolipoamide → FADD) 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) 1.5B) 2.5C) 3D) 10E) 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. A2. C3. B4. D5. A