Chapter 17: The Citric Acid Cycle

Question 1

Pyruvate dehydrogenase complex

Answer 1

A group of 3 enzymes and 5 coenzymes

Oxidizes pyruvate to acetyl-CoA & one CO₂

Produces one NADH

Question 2

Pyruvate dehydrogenase complex inhibition

Answer 2

The key means of regulating the complex is covalent modification via phosphorylation

PDH is allosterically inhibited by:

• ATP
• NADH
• acetyl CoA
• High ATP:ADP ratio

PDH is activated by:

• ADP
• NAD⁺
• Pyruvate
• Low ATP:ADP ratio

Question 3

Citric acid cycle enzymes

Answer 3

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1. Citrate synthase
   
   1. Inhibited by citrate and ATP
2. Aconitase
3. Isocitrate dehydrogenase- rate limiting
   
   1. Inhibited by NADH
   2. Stimulated by ADP and Ca²⁺
4. a-ketoglutarate dehydrogenase
   
   1. Inhibited by NADH, succinyl CoA, and acetyl CoA
   2. Stimulated by Ca²⁺
5. Succinyl CoA synthetase
6. Succiniate dehydrogenase
7. Fumarase
8. Malate dehydrogenase

Question 4

Citric acid cycle intermediates

Answer 4

Intermediates

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1. Citrate
2. Isocitrate
3. a-Ketoglutarate
4. Succinyl CoA
5. Succinate
6. Fumarate
7. Malate
8. Oxaloacetate

Question 5

Step 1 of CAC

Answer 5

Citrate synthase catalyzes the condensation of acetyl CoA and oxaloacetate to form citrate

Inhibited by:

• ATP
• NADH
• Succinyl-CoA
• Citrate

Question 6

Step 2 of CAC

Answer 6

Aconitase catalyzes a dehydration that forms the intermediate cis-aconitate

Cis-aconitate is subsequently hydrated to form isocitrate

Question 7

Step 3 of CAC

Answer 7

Isocitrate dehydrogenase catalyzes the oxidative decarboxylation of isocitrate forming α-ketoglutarate

Produces one molecule of NADH

Releases one molecule of CO₂

Inhibited by:

• ATP
• NADH

Stimulated by:

• ADP
• NAD⁺

Question 8

Step 4 of CAC

Answer 8

The α-ketoglutarate dehydrogenase complex catalyzes the synthesis of succinyl CoA

Produces one molecule of NADH

Releases one molecule of CO₂

Inhibited by:

• ATP
• NADH
• Succinyl-CoA

The enzyme is an organized assembly of three kinds of enzymes that is homologous to the pyruvate dehydrogenase complex

Question 9

Step 5 of CAC

Answer 9

Succinyl CoA synthetase catalyzes the cleavage of a thioester linkage forming succinate

Concomitantly forms one molecule of ATP/GTP via substrate-level phosphorylation

Question 10

Step 6 of CAC

Answer 10

Succinate dehydrogenase performs an elimination reaction that forms a E alkene fumarate

Produces one molecule of FADH₂

Question 11

Step 7 of CAC

Answer 11

Fumarase performs a hydration reaction that introduces the only chiral CAC intermediate malate

Question 12

Step 8 of CAC

Answer 12

Malate dehydrogenase oxidizes malate to reform oxaloacetate

Produces one molecule of NADH

Question 13

Citric acid cycle phases and net products

Answer 13

Pyruvate oxidation- yields one NADH, one acetyl CoA, and one CO₂ as waste

Citric acid cycle- yields one ATP, three NADH, one FADH₂, and two CO₂ as waste

Inputs and outputs shown are for each pyruvate molecule thus, each glucose molecule nets:

• 2 ATP
• 8 NADH
• 2 FADH₂

Question 14

Yields of each stage of cellular respiration

Answer 14

Per molecule of glucose

Glycolysis

• 2 ATP via substrate-level phosphorylation
• 2 NADH
• 2 Pyruvate

Pyruvate oxidation

• 2 NADH
• 2 Acetyl CoA

Citric acid cycle

• 2 ATP via substrate-level phosphorylation
• 6 NADH
• 2 FADH₂

Oxidative phosphorylation

• Roughly 26-28 ATP

Total ATP

Maximum 30-32 ATP

Question 15

Control points of CAC

Answer 15

Question 16

CAC source for fatty acids and sterols

Answer 16

Citrate

Question 17

CAC source for glutamate and purines

Answer 17

α-Ketoglutarate

Question 18

CAC source for porphyrins & heme

Answer 18

Succinyl-CoA

Question 19

CAC source for aspartate purines, pyrimidines, & glucose

Answer 19

Oxaloacetate

Question 20

Anapleurotic reactions

Answer 20

Anaplerosis is the act of replenishing TCA cycle intermediates that have been extracted for biosynthesis (in what are called anaplerotic reactions).

The TCA cycle is a hub of metabolism, with central importance in both energy production and biosynthesis. Therefore, it is crucial for the cell to regulate concentrations of TCA cycle metabolites in the mitochondria. Anaplerotic flux must balance cataplerotic flux in order to retain homeostasis of cellular metabolism