Lecture 27 - Pentose Phostphate Pathway

Question 1

What is the function of glucose 6-phosphate dehydrogenase?

L27 S7

Answer 1

• oxidizes G6P to form a lactone
• reduces NADP+ to NADPH

rate limiting

Question 2

What is the function of lactonase?

L27 S7

Answer 2

-opens lactone by adding water to form 6-phosphogluconate

Question 3

What is the function of 6-phosphogluconate dehydrogenase?

L27 S7

Answer 3

• decarboxylates 6-phosphogluconate to form ribulose 5-phosphate
• reduces NADP+ to NADPH

Question 4

What are the main functions of NADPH?

L27 S8-9

Answer 4

• anabolism (synthesis of monomers

- reduction

Question 5

What is glutathione and what does it do?

L27 S10-13

Answer 5

Tripeptide of Glu, Cys, and Gly (GSH)

• interacts with proteins (alters disulfide bonds)
• inactivates peroxides

After use it is found as a dimer GSSG

• regenerated via NADPH
• ratio of GSH:GSSG is ~500:1

Question 6

What is significant about glucose 6-phosphate dehydrogenase deficiency (G6PDD)?

L27 S14

Answer 6

• most common genetic disease
• X-linked recessive
• reduced NADPH production (also less reduction capacity leading to oxidative stress)

Question 7

What are the main producers of NADPH?

L27 S15

Answer 7

• glucose 6-phosphate dehydrogenase
• isocitrate dehydrogenase (2 isozymes use NADP+ instead of NAD+)
• malic enzyme (ME1)

Question 8

Why can decreased G6PD function lead to hemolytic anemia?

L27 S15

Answer 8

The iron in heme must be reduced in order to bind O2.

If O2 is not bound, ROS will be produced.

Question 9

What is the structure of G6PD and what affects its structure?

L27 S17

Answer 9

Monomer:

• inactive
• favored in high [NADPH]

Dimer:
-active

Tetramer:

• active
• favored in high [NAD+]

Question 10

How are AT ad G6PD related?

L27 S18

Answer 10

In AT, the ATM protein is mutated. This protein activates HSP27 which promotes dimerization of G6PD.

Without dimerized G6PD, less NADPH is produced.

Question 11

What are the regulators of G6PD?

L27 S19

Answer 11

Activators:

• dimerization
• transcription factors of antioxidants
• cell cycle/synthesis activators
• insulin

Inhibitors:

• phosphorylation
• apoptotic signaling

Question 12

What is the function of ribulose 5-phosphate isomerase?

L27 S21

Answer 12

Converts ribulose 5-phosphate to ribose 5-phosphate.

Question 13

What is the function of ribulose 5-phosphate epimerase?

L27 S21

Answer 13

Converts ribulose 5-phosphate to xylulose 5-phosphate.

Question 14

What is the function of transketolase?

L27 S22

Answer 14

Transfers 2-C from xylulose 5-phosphate.

Adds to ribose 5-phosphate to make sedoheptulose 7-phosphate.

-or-

Adds to erythrose 4-phosphate to make fructose 6-phosphate.

*transition states are stabilized by TPP (vitamin B1)

Question 15

What is the function of transaldolase?

L27 S23

Answer 15

Transfers 3-C units in the form of G3P.

From sedoheptulose 7-phosphate to erythrose 4-phosphate.

Question 16

What products of the pentose phosphate pathway are used to regenerate glucose 6-phosphate?

L27 S24

Answer 16

• F6P

- G3P