Citric Acid Cycle

Question 1

What are the three stages of Energy metabolism and cellular respiration?

Answer 1

Oxidation of precursors to yield Acetyl-CoA

Acetyl groups are oxidized to CO2 in CAC resulting in NADH and FADH2

Energy in NADH and FADH2 used to make ATP

Question 2

Where is the majority of energy obtained?

Answer 2

Complete oxidation of pyruvate in the mitochondria

Question 3

What are the four fates of pyruvate?

Answer 3

Lactate

Alanine

Acetyl CoA

Oxaloacetate

Question 4

What happens to acetyl CoA in the CAC?

Answer 4

Completely oxidized to CO2 in CAC

Question 5

What are the three enzymes in PDH?

Answer 5

Pyruvate Dehydrogenase

Dihydrolipoyl Transacetylase

Dihydrolipoyl Dehydrogenase

Question 6

What 5 coenzymes are required for the PDH?

Answer 6

TPP

Lipoate

Coenzyme A

FAD+

NAD+

Question 7

How is the PDH complex regulated by phosphorylation?

Answer 7

Inactivated by phosphorylation

Activated by dephosphorylation

Question 8

What activates PD kinase?

Answer 8

Allosteric: NADH, Acetyl CoA

Glucocorticoids, Insulin, Growth and Thyroid hormones, Tyr kinases

Question 9

What inhibits PD kinase?

Answer 9

Pyrvate, NAD, CoA

Question 10

What activates PD phosphatase?

Answer 10

Calcium, Low NADH/NAD ratio, Low Acetyl CoA levels

Question 11

What is generated in each turn of the CAC?

Answer 11

3 NADH

1 FADH2

One GTP

2CO2

Question 12

What is the first reaction?

Answer 12

Citrate Synthase - formation of citrate

Rate limiting step

Irreversible

Question 13

What is the second reaction?

Answer 13

Aconitase - formation of Isocitrate

Good substrate for oxidation

Reversible - product concentration kept low to pull forward

Question 14

What is the third reaction?

Answer 14

Isocitrate Dehydrogenase - formation of a-ketoglutarate

Oxidative decarboxylation

Generates CO2 and NADH

Irreversible

Question 15

What is the fourth reaction?

Answer 15

a-ketoglutarate dehydrogenase - forms Succinyl-CoA

Needs same five coenzymes used in PDH complex

Generates NADH

Irreversible

Question 16

Where do the carbons lost as CO2 come from?

Answer 16

Derived from oxacloacetate

Question 17

What is the fifth reaction?

Answer 17

Succinyl-CoA Synthetase - forms Succinate

Produces GTP

Reversible

Question 18

What is the sixth reaction?

Answer 18

Succinate Dehydrogenase - forms fumarate

Bound to inner membrane, part of ETC

Produces FADH2

Reversible

Question 19

What is the seventh reaction?

Answer 19

Fumarase - forms L-malate

Reversible

Question 20

What is the eighth reaction?

Answer 20

Malate Dehydrogenase - forms oxaloacetate

Unfavorable - oxaloacetate concentration kept very low by citrate synthase

Question 21

What are some examples of anaplerotic reactions that provide the CAC with intermediates to continue?

Answer 21

Pyruvate carboxylase - pyruvate to OAA

Malic Enzyme - Pyruvate to malate

PEP carboxykinase - PEP to OAA

Question 22

How do glucogenic amino acids contribute to the TCA cycle?

Answer 22

Degradation generates 3,4, or 5C intermediates of the TCA cycle

Question 23

How is citrate synthase regulated?

Answer 23

Activated: ADP

Inhibited: NADH, Succinyl-CoA, citrate ATP

Question 24

How is Isocitrate dehydrogenase regulated?

Answer 24

Activated: Ca, ADP

Inhibited: ATP

Question 25

How is a-ketoglutarate dehydrogenase complex regualted?

Answer 25

Activated: Ca

Inhibited: Succinyl-CoA, NADH

Question 26

What results from citric acid cycle defects?

Answer 26

Invariably affects the CNS

Wide range of phenotypes

Diagnosis depends on biochemical analysis

Extremely rare