PDC

Question 1

Under anaerobic conditions, 2 pyruvate are ______.

NADH is _______, why?

Answer 1

2 pyruvate reduced to 2 lactate

NADH is oxidized to NAD+ for regeneration for step 6 of glycolysis

Question 2

Under aerobic conditions, 2 pyruvate______

Answer 2

2 pyruvate will enter the mitochondria and pyruvate dehydrogenase complex will oxidize to 2 acetyl CoA

Also lose CO2 and produce 2 NADH in the process

Question 3

Where is PDC located?

Answer 3

mitochondrial matrix

Question 4

Major components of PDC?

Answer 4

E1, E2, E3

Question 5

Type of reaction PDC catalyzes

Answer 5

Oxidative decarboxylation

Oxidation reduction
NAD+ –> NADH
Loss of CO2

Question 6

Products of PDC catalyzed reaction per 1 glucose

Answer 6

2 Acetyl CoA
2 CO2
2 NADH

Question 7

Requirements for PDC reaction

Answer 7

Vitamin coenzymes

Question 8

Vitamin coenzymes (2)

Answer 8

1. Catalytic, covalently bound to respective components

2. Stoichiometric, not bound, come on and off complex

Question 9

Catalytic vitamin coenzymes

Answer 9

• Thiamin pyrophosphate (TPP)
• Lipoic acid
• Flavin adenine dinucleotide (FAD/FADH2)

Question 10

Stoichiometric, not bound vitamin coenzymes

Answer 10

• CoA

- NAD+

Question 11

Why are they called coenzymes?

Answer 11

Need to undergo the same type of regeneration of conformation following the reaction that an enzyme does

Question 12

Is the PDC reaction reversible or irreversible?

Answer 12

Irreversible

Question 13

3 Step Overview of PDC Reaction

Answer 13

1. Decarboxylation
2. Oxidation
3. Transfer to CoA

Question 14

1. Decarboxylation

Answer 14

Pyruvate lose a CO2

Results in carbonyl group with a negative charge (acetyl group)

Question 15

2. Oxidation

Answer 15

Lose 2 e- which are transferred to NAD+ –> NADH

Results in a carbonyl group with a positive charge (acetyl group)

Question 16

3. Transfer to CoA

Answer 16

Acetyl group is transferred to CoA to yield acetyl CoA

When you add acetyl group to CoA –> form a HIGH ENERGY THIOESTER BOND

Question 17

Where does decarboxylation happen?

Answer 17

On E1 which has TPP bound to it

Question 18

Goal of oxidation and transfer (2nd step)

Answer 18

Transfer the acetyl intermediate that is bound to TPP to E2, specifically the lipoamide

The 2 C orginating from pyruvate are now on E2 lipoamide

THIOESTER BOND IS FORMED

Question 19

origin of the lipoamide

Answer 19

E2 has lipoic acid coenzyme. When you attach the lipoic acid covalently to E2, it is bound to the lysine side chain –> form the lipoamide arm

Question 20

Significance of lipoamide on E2

Answer 20

Has an S-S bond

Makes a swinging arm that can go back and forth between E1 and E2 and E2 and E3 to “shuttle the 2 carbons”

Question 21

Transfer of 2C from E1 to E2 lipoamide arm is catalyzed by

Answer 21

E1 complex

Question 22

How does the transfer of acetyl group to CoA happen?

Significance?

Answer 22

Lipoamide arm swings over to CoA and transfer the acetyl group

Now, the thioester bond is on the Acetyl CoA molecule –> to be used in TCA cycle

Question 23

What is the transfer of acetyl group to CoA catalyzed by?

Answer 23

E2

Question 24

Oxidation of dihydrolipoamide purpose?

Answer 24

Resetting PDC to allow for another catalytic cycle

Question 25

How does oxidation of dihydrolipoamide happen?

Answer 25

1. E2 with lipoamide arm swings over to E3 which has FAD covalently bound –> FAD accepts electrons and becomes reduced to FADH2 –> S-S bond is formed again on the lipoamide arm so it is ready for another round
2. Then, NAD+ (which comes on and off complex) accepts the electrons from FADH2 to yield NADH and FAD regenerated

Catalyzed by E3

Question 26

Allosteric regulation of PDC

Answer 26

PDC less active when high energy charge

• ATP negative modifier
• Acetyl CoA and NADH feedback inhibit

PDC more active when low energy charge

• ADP positive modifier
• NAD+ and pyruvate concentrations too

Question 27

Hormonal regulation of PDC

Fasted state

Answer 27

Glucagon signaling predominates…..

Triggers phosphorylation by pyruvate dehydrogenase kinase –> inactivation of PDC

Question 28

Pyruvate dehydrogenase kinase regulation

Answer 28

Allosterically activated by NADH and Acetyl CoA as they are simultaneously feedback inhibiting PDC allosterically

Pyruvate and ADP allosterically inhibit

Question 29

Hormonal Regulation of PDC

Fed state

Answer 29

Insulin signaling predominates…..

PDC is dephosphorylated by phosphatase to activate

Question 30

Significance of PDC reaction

Answer 30

To generate a high energy thioester bond in acetyl CoA that can be used in TCA cycle

Question 31

All intermediates in PDC reaction are

Importance?

Answer 31

Covalently bound in some way to PDC throughout the entire reaction

Allows for efficiency- don’t have to wait for diffusion

Question 32

Insulin signaling in fed state always results in:

Answer 32

Dephosphorylation of enzymes in energy transducing or bio synthetic pathways

Question 33

PDK-1, PDC, pyruvate kinase are all regulated by:

Trend?

Answer 33

Energy charge

Activity is decreased when ATP levels are elevated because ATP is a negative allosteric modifier of all of them