M1: Pentose Phosphate Pathway L5

Question 1

A loss of function mutation in which enzymes would cause fructosemia (fructose intolerance)?

Answer 1

Fructokinase and Fructose-1-phosphate aldolase.

Question 2

Describe what glucpse-6-phosphate dehydrogensase (G6PDH) deficiency is.

Answer 2

G6PDH wild type protects red blood cells from reactive oxygen species. When you get an infection or take certain drugs that increase H2O2 (peroxide) the mutated G6PDH will not be able to protect the cell from degradation by reactive oxygen species. People with this deficiency will have a shorter red blood cell lifespan. The phenotype can manifest itself as hemolytic anemia or even jaundice.

Question 3

At what intermediate of glycolysis does the pentose phosphate pathway branch off from?

Answer 3

Glucose-6-phosphate (G6P).

Question 4

At what intermediate of glycolysis does the pentose phosphate pathway branch back in?

Answer 4

Fructose-6-phosphate and GAP.

Question 5

What is the committing enzyme of the pentose phosphate pathway?

Answer 5

G6PDH: glucose-6-phosphate dehydrogenase. Irreversible step.

Question 6

Where does the pentose phosphate pathway take place?

Answer 6

1. Liver
2. Adipose tissue
3. Red blood cells

Question 7

Where does the pentose phosphate pathway NOT take place?

Answer 7

Muscle.

Question 8

What is NADP+/NADPH generated from?

Answer 8

The pentose phosphate pathway.

Question 9

What are the metabolic uses of NADP+/NADPH?

Answer 9

1. Fatty acid and cholesterol biosynthesis (lipids)

2. Reduction reactions

Question 10

What is the role of glutathione peroxidase (GSH) in red blood cells?

Answer 10

It prevents peroxide-mediated hemolysis of red blood cells.

Question 11

What is the reaction involving GSH and organic hydroperoxides?

Answer 11

2GSH + ROOH —glutathione peroxidase–> GSSG + ROH + H2O

Question 12

What is the reaction that recycles GSH?

Answer 12

GSSG + NAPDH + H+ –Glutathione reductase–> 2GSH + NADP+

Question 13

What compound is needed to maintain the pool of GSH which prevents hemolysis or RBC’s?

Answer 13

NADPH

Question 14

Describe how G6PDH and NADPH relate in the protection against hemolysis.

Answer 14

1. A deficiency in G6PDH causes low amounts of NADPH since GSPDH is the committing enzyme of the pentose phosphate pathway.
2. Low NADPH makes it harder for the cell to keep [GSH] high
3. The RBC’s cannot handle the extra oxidants
4. There is damage to the cell membranes => hemolysis

Question 15

What allosterically modifies G6PDH and in what way?

Answer 15

High [NADPH] allosterically inhibits G6PDH.

Question 16

In what phase of the pentose phosphate pathway do you get NADPH?

Answer 16

The oxidative phase.

Question 17

Write out the pentose phosphate pathway.

Answer 17

L5.1 S26

Question 18

How many NADPHs and ribulose-5-phosphates (Ru5P) are generated for each G6P used in the pentose phosphate pathway?

Answer 18

2 NADPH/G6P

1 Ru5P/G6P

Question 19

how many glucose-6-phosphates (G6P) go into the pentose phosphate pathway?

Answer 19

3 G6Ps

Question 20

What is isomerization?

Answer 20

The interchange of groups between carbons.

Question 21

What is epimerization?

Answer 21

The interchange of groups on a single carbon.

Question 22

What is the purpose of the isomerization and epimerization reactions?

Answer 22

To produce ribose-5-phosphate (R5P).

Question 23

How many Ribose-5-phosphates (R5P) and Xylulose-5-phosphates (Xu5P) are made from 3 Ribulose-5-phosphates (Ru5P)?

Answer 23

3 Ru5P –> 1 R5P + 2 Xu5P

Question 24

What is the overall pentose phosphate pathway stoichiometry?

Answer 24

3 G6P + 6 NADP+ + 3H2O –> 6 NADPH + 6 H+ + 3 CO2 + 2 F6P + 1 GAP

Question 25

How does the cell decide how to metabolize G6P?

Answer 25

It decides bases off of its needs of ATP, NADPH, and RIbose-5-phosphate.

Question 26

How would the pentose phosphate pathway be regulated if the cell needs both NADPH and nucleotides?

Answer 26

• NADPH and R5P are both produced
• R5P will make nucleotides.
• Excess R5P + Xu5P are recycled back to F6P and GAP.

Question 27

How would the pentose phosphate pathway be regulated if the cell needs NADPH only?

Answer 27

• NADPH and R5P are produced
• No nucleotides are made from R5P
• Excess R5P + Xu5P are recycled back to F6P and GAP.

Question 28

How would the pentose phosphate pathway be regulated if the cell needs nucleotides only?

Answer 28

The forward reaction of the pentose phosphate pathway would be inhibited by G6PDH because of the high [NADPH]. So, F6P and GAP are used for the synthesis of R5P by the reversal of the transaldolase and transketolase reactions. R5P will then be used to produce nucleotides and no NADPH is produced.