Lecture 24: TCA Cycle

Question 1

Three steps in formation of Acetyl CoA from pyruvate

Answer 1

Decarboxylation
Oxidation
Transfer to CoA
NADH is produced

Question 2

How does pyruvate enter the mitochondria, and what decarboxylates it once inside

Answer 2

Mitochondrial pyruvate carrier

Pyruvate dehydrogenase complex

Question 3

Pyruvate dehydrogenase requires _ enzymes and _ coenzymes- name them

Answer 3

3 enzymes E1, E2, E3
5 coenzymes 
-Thyamine pyrophosphate
Lipoic acid
FAD
NAD
CoA

Question 4

Pyruvate dehydrogenase is active under which phosphorylation state

Answer 4

Dephosphorylated is active

Question 5

What are positive/negative allosteric regulators of Pyruvate dehydrogenase kinase PDK

Answer 5

+ Acetyl Coa, NADH, ATP

- Pyruvate, CoA, NAD+, ADP

Question 6

What are positive allosteric regulators of Pyruvate dehydrogenase phosphatase PDP

Answer 6

Calcium and magnesium

Question 7

High levels of acetyl CoA will directly inhibit which enzyme of the pyruvate dehydrogenase complex (remember 3 enzymes and 5 coenzymes)

Answer 7

E2

Question 8

Citrate synthase

Answer 8

Condensation of 4-carbon oxaloacetate and 2-carbon acetyl CoA to yield Citrate

Question 9

Aconitase

Answer 9

Citrate –> Isocitrate

Question 10

Isocitrate dehydrogenase

Answer 10

Isocitrate-->oxalosuccinate--> a-ketoglutarate
NADH + CO2 formed
Rate limiting step
Activated by ADP
Inhibited by ATP and NADH

Question 11

a-ketoglutarate dehydrogenase complex

Answer 11

a-ketoglutarate–> Succinyl CoA
NADH formed
Inhibited by ATP, succinyl CoA and NADH

Question 12

Succinyl CoA synthetase

Answer 12

Succinyl CoA–> Succinate

*GTP formed- only step yielding high energy molecule

Question 13

Succinate dehydrogenase

Answer 13

Succinate–> Fumarate

FADH2 formed

Question 14

Where is succinate dehydrogenase located, and where is FADH2 sent when formed by it

Answer 14

Located in the inner mitochondrial membrane directly associated with electron transport chain
FADH2 passes electrons directly to Co-Q in the ETC

Question 15

Fumarase

Answer 15

Fumarate–> Malate

Question 16

Malate dehydrogenase

Answer 16

Malate–> Oxaloacetate
NADH formed
Inhibited by excess oxaloacetate or NADH

Question 17

How does insulin help regulate the citric acid cycle

Answer 17

Insulin can stimulate fatty acid synthesis by activating phosphatases and increasing conversion of pyruvate to acetyl CoA

Question 18

What is the effect of Arsenite on pyruvate dehydrogenase complex

Answer 18

Inhibits function by binding Lipoic acid on E2

Question 19

How does citrate synthase prevent wasteful hydrolysis of Acetyl CoA

Answer 19

Oxaloacetate must bind first, and the enzyme undergoes conformational change to accept acetyl CoA

Question 20

What is the second control site in the citric acid cycle

Answer 20

Isocitrate dehydrogenase is activated by ADP and inhibited by NADH/ATP

Question 21

What is the third control site in the citric acid cycle

Answer 21

a-ketoglutarate dehydrogenase
Allosterically inhibited by its products- Succinyl CoA and NADH
Also inhibited by ATP

Question 22

What happens when excess citrate builds up because of the control point at isocitrate dehydrogenase, what happens to the citrate

Answer 22

It is transported to the cytosol and signals phosphofructokinase to halt glycolysis

Question 23

What happens to a-ketoglutarate when it builds up

Answer 23

It can be used for synthesis of amino acids and purine bases

Question 24

What are the two major anaplerotic reactions that replenish TCA cycle intermediates- and when are they important

Answer 24

Degradation of amino acids
Carboxylation of pyruvate
Most important during states of low energy