Carbohydrate Metabolism: Pentose Phosphate Pathway

Question 1

What is the Pentose Phosphate Pathway (PPP) also known as?

Answer 1

The Phosphogluconate Pathway

The Hexose Monophosphate Shunt/Pathway

Question 2

Where does the PPP occur?

Answer 2

Cytosol

Question 3

PPP is the oxidation of _____

Answer 3

Oxidation of Glucose-6-P

Question 4

What is the electron acceptor in PPP?

Answer 4

NADP+

Question 5

What phases are included in the PPP?

Answer 5

Oxidative

Non oxidative

Question 6

How is flux controlled in the PPP?

Answer 6

Dependent on

• If NADPH is required
• If nucleotide pool needs to be replenished
• If ATP levels are low

Question 7

What is Ribose-5-phosphate (R5P) and where is it utilized in PPP?

Answer 7

R5P is a biosynthetic precursor of nucleotides needed for

• DNA and RNA synthesis
• Synthesis of ATP, NAD+, FAD, Coenzyme A, etc.

Question 8

Who are the main users of R5P?

Answer 8

Rapidly dividing cells

- Such as bone marrow, skin, intestinal mucosa, tumors

Question 9

Where is NADPH utilized in PPP?

Answer 9

Tissues with active reductive biosynthesis

• Liver, adipose, lactating mammary glands (fatty acid synthesis)
• Liver, adrenal glands, gonads (cholesterol and steroid hormones synthesis)

Tissues that need to counter damaging effects of oxygen radicals
- Erythrocytes, Cells of the lens and cornea: directly exposed to O2

Question 10

Describe the oxidative phase of the PPP.

Answer 10

Converts 6 molecules of glucose-6-P to 6 molecules of ribulose-5-P, resulting in the production of 2 NADPH and 1 CO2

The enzyme Glucose-6-phosphate dehydrogenase catalyzes an irreversible reaction that represents the commitment step in the pathway.

Question 11

What is the commitment step in the oxidative phase of PPP?

Answer 11

When Glucose-6 phosphate dehydrogenase catalyzes the irreversible reaction of Glucose-6-P to 6-Phosphogluconolactone using up a NADP+

Question 12

Describe the initial steps for the non-oxidative phase of PPP.

Answer 12

AKA Carbon Shuffle Reactions

6 Ribulose-5-P are converted into 4 F6P and 2 GAP using carbon shuffle reactions

Some of the carbon shuffle reactions and enzymes used here are similar to those seen in the Regeneration stage of the Calvin Cycle.

Question 13

What is the net outcome of the initial steps of the non-oxidative phase of PPP?

Answer 13

6 Ru-5-P generated in the oxidative phase are converted to 4 molecules of F6P and 2 molecules of GAP (G3P)

Question 14

What does Transketolases do in the non-oxidative phase of PPP?

Answer 14

Transketolases catalyze transfer of a 2C group from a donor to an acceptor

Question 15

What does Transaldolases do in the non-oxidative phase of PPP?

Answer 15

Transaldolases catalyze transfer of a 3C group from a donor to acceptor

Question 16

What are specific to the non-oxidative phase of PPP?

Answer 16

Ribose-5-P isomerase, Ribulose-5-P epimerase, Transketolase and Transaldolase

Question 17

Desribe the final steps for the non-oxidative phase of PPP.

Answer 17

G6P is regenerated from F6P and GAP by enzymes in the glycolytic and/or gluconeogenic pathway.

Overall, the non-oxidative phase of the PPP converts 6 molecules of ribulose-5-P to 5 molecules of glucose-6-P

6x5 = 30 molecules can be made, 5 glucose can be made.

REMEMBER REACTION!!! WILL BE ON TEST

Question 18

What enzymes of the non-oxidative phase are components of glycolytic pathway and the gluconeogenic pathway?

Answer 18

Phosphoglycoisomerase

Triose phosphate isomerase

Aldolase

Question 19

What is unique to the gluconeogenic pathway?

Answer 19

Fructose-1,6-bisphosphate-1 (FBPase-1)

Question 20

Which part of the PPP is favorable?

Answer 20

Oxidative part:
deltaG’* &laquo_space;0
VERY favorable

Non-oxidative part:
deltaG’* =~ 0 (approx. 0)

Question 21

What is the rate limiting step in the PPP?

Answer 21

G6PDH

Enzyme that limits the rate

Question 22

How is G6PDH activity regulated?

Answer 22

G6DPH activity is allosterically regulated by [NADP+]-to-[NADPH] ratio in the cell

Allosteric activator = NADP+, there is high amounts of NADP+

Allosteric inactivator = NADPH, there is high amounts of NADPH

Question 23

What happens if there is excess amounts of NADPH?

Answer 23

If there is an excess amount of NADPH, you shouldn’t be doing PPP and instead be doing glycolysis creating ATP.

Question 24

NADPH is used in _______ as well as _______ pathways

Answer 24

used in biosynthetic as well as detoxification pathways

Question 25

What is the role of NADPH in detoxification?

Answer 25

NADPH is required as a coenzyme in the lutathione reductase reaction to convert oxidized glutathione (GSSG) to reduced glutathione (GSH).

Buildup of harmful oxygen radicals in cells is prevented by detoxification reactions that require reduced glutathione and the enzyme glutathione peroxidase

Question 26

Why does G6PDH have a role in PPP because of the role of NADPH?

Answer 26

The G6PDH reaction in the PPP is required to generate sufficient levels of NADPH in RBCs to maintain high levels of GSH

Question 27

What is G6PDH Deficiency?

Answer 27

Affects ~400 million people worldwide (common)

Most are asymptomatic

Combination of certain environmental factors and G6PDH produces clinical manifestations

Can be fatal in cases of high oxidative stress:

• Certain drugs (Primaquine, Sulfa antibiotics)
• Some herbicides
• Some foods (fava beans, an ingredient of falafal)

Question 28

What is favism?

Answer 28

Vicine, the toxic ingredient of fava beans, generates reactive oxygen species as metabolic by-products

Normal individuals can handle this, but not G6PDH-deficient people which develop the condition Favism:

RBCs lyse within 24-48 hrs, releasing Hb

Jaundice and kidney failure can occur

Favism can prove fatal

Question 29

If you are deficient in G6PDH, what is an advantage that you have?

Answer 29

Resistance to malaria

Malaria parasite extremely sensitive to oxidative stress

Parasite killed by the level of oxidative stress that is tolerable to a G6PDH-deficient human host