Regulation of Pyruvate Dehydrogenase

Question 1

True or false: The conversion of pyruvate to acetyl CoA by pyruvate dehydrogenase is reversible.

Answer 1

False; it is irreversible.

Question 2

Which compounds are competitive inhibitors of pyruvate dehydrogenase?

Answer 2

NADH and acetyl-CoA (the products of the reaction)

Question 3

True or false: NAD+ is a competitive inhibitor of pyruvate dehydrogenase.

Answer 3

False; NADH is a competitive inhibitor (competes for NAD+ binding site)

Question 4

True or false: Acetyl-CoA is a competitive inhibitor of pyruvate dehydrogenase.

Answer 4

True

Question 5

What two molecules actually drive the E2 and E3 reactions of pyruvate dehydrogenase in reverse?

Answer 5

NADH and acetyl-CoA

Question 6

What is the effect of high ratios of [NADH]/[NAD+] and [acetyl-CoA]/[CoA]?

Answer 6

Maintains E2 in acetylated form, making it incapable of accepting hydroxyethyl group from TTP

Question 7

Which part of pyruvate dehydrogenase reaction is inhibited by NADH?

Answer 7

The dihydrolipoyl dehydrogenase (E3).

Question 8

Which part of pyruvate dehydrogenase reaction is inhibited by acetyl-CoA?

Answer 8

The transacetylase component (E2), because acetyl-CoA binds to it.

Question 9

To what fate does the oxidative carboxylation of pyruvate to acetyl-CoA commit the carbon atoms derived from glucose?

Answer 9

Either oxidation to CO2 by the TCA cycle and generation of energy or incorporation into lipid (because acetyl-CoA is a precursor for lipid synthesis).

Question 10

What are the two key means of regulating pyruvate dehydrogenase?

Answer 10

1) Competitive inhibition by NADH and acetyl CoA

2) Covalent modification of E1 by pyruvate dehydrogenase kinase that inactivates the enzyme.

Question 11

Which hormone reverses the inactivation of pyruvate dehydrogenase kinase by activating pyruvate dehydrogenase phosphatase?

Answer 11

Insulin

Question 12

What activates pyruvate dehydrogenase kinase?

Answer 12

NADH and acetyl-CoA

Question 13

When activated, what does pyruvate dehydrogenase kinase do to pyruvate dehydrogenase?

Answer 13

It causes phosphorylation that inactivates the multi-enzyme complex.

Question 14

Which enzyme, when activated by insulin, reverses the effects of pyruvate dehydrogenase kinase? How does it do this?

Answer 14

Pyruvate dehydrogenase phosphatase; it removes phosphoryl groups, reactivating pyruvate dehydrogenase and allowing the TCA Cycle to continue.

Question 15

What causes insulin to promote the synthesis of acetyl-CoA and glycogen?

Answer 15

Increased [glucose].

Question 16

True or false: the phosphorylated E1 enzyme is active.

Answer 16

False; the dephosphorylated E1 enzyme is active.

Question 17

What causes the deactivation of the E1 enzyme?

Answer 17

Phosphorylation by pyruvate dehydrogenase kinase, which is activated by increase concentrations of NADH and Acetyl-CoA

Question 18

What inhibits pyruvate dehydrogenase kinase?

Answer 18

Pyruvate, ADP, and Ca+

Question 19

True or false: pyruvate dehydrogenase is activated by cAMP.

Answer 19

False; it is unaffected by cAMP.

Question 20

True or false: Ca2+ (released in response to hormones) activates pyruvate dehydrogenase kinase and inhibits pyruvate dehydrogenase phosphatase.

Answer 20

False; Ca2+ inhibits pyruvate dehydrogenase kinase and activates pyruvate dehydrogenase phosphatase.