Module 4 - Pentose Phosphate Pathway

Question 1

Glucose-6-Phosphate Dehydrogenase

Answer 1

This enzyme catalyzes the first committed step in the PPP and is rate-limiting

Question 2

NADPH

Answer 2

A major product of the PPP and the major currency of reducing equivalents in the cell that are used in a variety of biosynthetic reactions.

Question 3

Pentose Phosphate Pathway

Answer 3

A pathway for glucose degradation that yields ribose 5-phosphate and NADPH.

Question 4

Transaldolase and Transketolase

Answer 4

Two enzymes that catalyze reversible reactions in the non-oxidative phase of the PPP that interconvert 3-, 4-, 5-, 6-, and 7-carbon sugars.

Question 5

What is the major role of PPP?

Answer 5

to produce NADPH, the major currency for reducing equivalents in the cell, and ribose-5-P, which is the sugar component of nucleotides

Question 6

What is the starting point for PPP?

Answer 6

glucose-6-P is the starting point for this pathway, and is also an intermediate of glycolysis, these pathways are interconnected

Question 7

Production of NADPH

Answer 7

plants produce NADPH through photosynthesis,

non-photosynthetic organisms generate NADPH through the PPP.

Question 8

Where is the PPP active in animals?

Answer 8

where the synthesis of biomolecules occurs at high rates

Question 9

What are the two phases of this pathway?

Answer 9

In the first part, the oxidative phase, glucose-6-P is oxidized and in the process, NADP+ gets reduced to NADPH.

In the second phase, the non-oxidative phase, ribulose-5-P is converted to ribose-5-P which is the second major product of this pathway.

Question 10

How is the PPP connected to Glycolysis?

Answer 10

the second phase of the pathway is also where the interconversion of 3-, 4-, 5-, 6-, and 7-carbon sugars takes place.

These interconversions provide a way for the excess 5-carbon sugars to be converted to intermediates of glycolysis.

It is a way to divert the excess ribose-5-P to glycolysis where it can be metabolized into useful components and/or to produce ATP

Question 11

Phase 1 - Oxidative Phase

Answer 11

The pathway starts with glucose-6-P, which is an intermediate of both glycolysis and gluconeogenesis

for every glucose-6-P molecule that enters the pathway, two NADPH are produced.

Ribulose-5-P, a 5-carbon sugar, is the end-product of this phase

Question 12

Phase 2: Non-Oxidative Phase

Answer 12

The major goal of this phase is to convert ribulose-5-P to ribose-5-P, which is catalyzed by an isomerase

Question 13

What are the glycolytic intermediates of Ribose-5-P?

Answer 13

These reversible conversions are catalyzed by two enzymes, transketolase and transaldolase

the products of these reactions include glyceraldehyde-3-P and fructose-6-P, both of which are glycolytic intermediates

Question 14

How is the PPP regulated?

Answer 14

The most important point to remember about the regulation of the PPP is that it is the cytosolic concentration of NADP+ which plays the biggest role.

Question 15

What is the rate-limiting step?

Answer 15

the very first step of this pathway is catalyzed by glucose-6-P dehydrogenase.

This pathway is the rate-limiting step i.e., the slowest step

Question 16

How is glucose-6-P metabolized?

Answer 16

glucose-6-P can be metabolized by both glycolysis and the PPP, since both pathways take place in the cytosol

the fate of glucose-6-P is highly dependent on the cell’s need for NADPH.

If the need is low, then more will be metabolized through glycolysis.

If there is high demand for NADPH, more will be metabolized through the PPP.

Question 17

Coordinated regulation between glycolysis and PPP

Answer 17

the decision as to whether glucose-6-P will be metabolized by glycolysis or the PPP is also guided by the need of the cell for ribose-5-P and ATP which are important products of the PPP and glycolysis

Question 18

What happens when the need for ribose-5-P is greater than the need for NADPH?

Answer 18

arises in cells that are rapidly dividing and have to synthesize a lot of DNA

most of the glucose-6-P is metabolized through glycolysis to fructose-6-P and glyceraldehyde-3-P

These two molecules can then be used by the non-oxidative portion of the PPP, using the reversible reactions catalyzed by transketolase and transaldolase, to produce ribose-5-P

Question 19

What happens when the need for NADPH and ribose-5-P are about the same?

Answer 19

glucose-6-P is metabolized through the oxidative portion of the PPP where NADPH is produced.

The ribulose-5-P that is produced is converted to ribose-5-P.

This results in the replenishment of both NADPH and ribose-5-P.

Question 20

What happens when the need for NADPH is greater than that for ribose-5-P?

Answer 20

occurs in liver,

there are three sets of reactions that in the end result in the complete oxidation of glucose-6-P to CO2 with the formation of NADPH.

First, glucose-6-P is converted to ribulose-5-P by the oxidative portion of the PPP which results in NADPH production.

The ribulose-5-P that is produced is easily and rapidly converted to ribose-5-P, which is then converted to fructose-6-P and glyceraldehyde-3-P by the non-oxidative reactions of the PPP.

These two metabolites can then be used in gluconeogenesis to produce glucose-6-P.

If one writes out the stoichiometry of all three of these reaction sets, one finds that every glucose-6-P is oxidized to 6CO2 with 12 NADPH produced.

Question 21

What happens when both NADPH and ATP are required?

Answer 21

glucose-6-P is metabolized through the oxidative portion of the PPP which produces NADPH.

The ribulose-5-P produced is converted to fructose-6-P and glyceraldehyde-3-P by the non-oxidative portion of the PPP.

Both of these metabolites can then enter glycolysis and be metabolized to pyruvate, which produces ATP.