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Biochemistry: A Short Course

First Edition

Biochemistry: A Short Course

First Edition

Tymoczko • Berg • Stryer

© 2010 W. H. Freeman and Company

CHAPTER 25

The Pentose Phosphate Pathway

The Pentose Phosphate

Pathway Generates NADPH and

Synthesizes Five-Carbon Sugars

The pentose phosphate pathway

meets the need of all organisms

for a source of NADPH to use in

reductive biosynthesis. This

pathway consists of two phases:

1. The oxidative generation of

NADPH

2. and the nonoxidative

interconversion of sugars.

In the oxidative phase, NADPH

In the oxidative phase, NADPH

is generated when glucose 6-

is generated when glucose 6-

phosphate is oxidized to

phosphate is oxidized to

ribose 5-phosphate

ribose 5-phosphate

This five-

This five-

carbon sugar and its

carbon sugar and its

derivatives are components of

derivatives are components of

RNA and DNA, as

RNA and DNA, as

well as ATP, NADH,

well as ATP, NADH,

FAD, and coenzyme

FAD, and coenzyme

A

A

Two Molecules of NADPH Are Generated in the Conversion of Glucose 6-phosphate

Two Molecules of NADPH Are Generated in the Conversion of Glucose 6-phosphate

into Ribulose 5-phosphate

into Ribulose 5-phosphate

The oxidative phase of the pentose phosphate pathway starts with the

The oxidative phase of the pentose phosphate pathway starts with the

dehydrogenation of glucose 6-phosphate at carbon 1, a reaction catalyzed by

dehydrogenation of glucose 6-phosphate at carbon 1, a reaction catalyzed by glucose

glucose

6-phosphate dehydrogenase

6-phosphate dehydrogenase

. The product is . The product is 6-phosphoglucono-δ-lactone

6-phosphoglucono-δ-lactone , which is an

, which is an

intramolecular ester between the C-1 carboxyl group and the C-5 hydroxyl group. The

intramolecular ester between the C-1 carboxyl group and the C-5 hydroxyl group. The

next step is the hydrolysis of 6-phosphoglucono-δ-lactone by a specific

next step is the hydrolysis of 6-phosphoglucono-δ-lactone by a specific lactonase

lactonase to

to

give

give 6-phosphogluconate

6-phosphogluconate

. This six-carbon sugar is then oxidatively decarboxylated by . This six-carbon sugar is then oxidatively decarboxylated by

6-phosphogluconate dehydrogenase

6-phosphogluconate dehydrogenase to yield

to yield ribulose 5-phosphate

ribulose 5-phosphate .

NADP

NADP

++

is again the

is again the

electron acceptor.

electron acceptor.

The Pentose Phosphate Pathway and Glycolysis Are Linked by

The Pentose Phosphate Pathway and Glycolysis Are Linked by

Transketolase and Transaldolase.

Transketolase and Transaldolase.

The preceding reactions yield

The preceding reactions yield two molecules of NADPH

two molecules of NADPH and

and one

one

molecule of ribose 5-phosphate

molecule of ribose 5-phosphate for each molecule of glucose 6-

for each molecule of glucose 6-

phosphate oxidized.

phosphate oxidized.

However, many cells need NADPH for reductive biosyntheses much

However, many cells need NADPH for reductive biosyntheses much

more than they need ribose 5-phosphate for incorporation into

more than they need ribose 5-phosphate for incorporation into

nucleotides and nucleic acids.

nucleotides and nucleic acids.

In these cases, ribose 5-phosphate is converted into

In these cases, ribose 5-phosphate is converted into

glyceraldehyde 3-phosphate and fructose 6-phosphate by

glyceraldehyde 3-phosphate and fructose 6-phosphate by

transketolase

transketolase and

and transaldolase

transaldolase

. These enzymes create a . These enzymes create a reversible

reversible

link

link between the

between the pentose phosphate pathway and glycolysis by

pentose phosphate pathway and glycolysis by

catalyzing these three successive reactions.

catalyzing these three successive reactions.

three reactions linking the

three reactions linking the pentose

pentose

phosphate pathway and glycolysis

phosphate pathway and glycolysis is the

is the

formation of

formation of

glyceraldehyde 3-phosphate

glyceraldehyde 3-phosphate

and

and

sedohep-tulose 7-phosphate

sedohep-tulose 7-phosphate

from two

from two

pentoses.

pentoses.

transketolase

transketolase catalyzes the synthesis of

catalyzes the synthesis of

fructose 6-phosphate

fructose 6-phosphate and

and glyceraldehyde 3-

glyceraldehyde 3-

phosphate

phosphate from erythrose 4-phosphate and

from erythrose 4-phosphate and

xylulose 5-phosphate.

xylulose 5-phosphate.

The Flow of Glucose 6-

The Flow of Glucose 6-

phosphate Depends on the Need

phosphate Depends on the Need

for NADPH, Ribose 5-phosphate,

for NADPH, Ribose 5-phosphate,

and ATP

and ATP

Mode 1. Much more ribose

5-phosphate than NADPH is

required. For example,

rapidly dividing cells need

ribose 5-phosphate for the

synthesis of nucleotide

precursors of DNA Most of

the glucose 6-phosphate is

converted into fructose 6-

phosphate and

glyceraldehyde 3-phosphate

by the glycolytic pathway.

Transaldolase and

transketolase then convert

two molecules of fructose 6-

phosphate and one molecule

of glyceraldehyde 3-

phosphate into three

molecules of ribose 5-

phosphate

Mode 2. The needs for NADPH and ribose 5-

phosphate are balanced. The predominant reaction

under these conditions is the formation of two

molecules of NADPH and one molecule of ribose

5-phosphate from one molecule of glucose 6-

phosphate in the oxidative phase of the pentose

phosphate pathway.

Mode 3.

Mode 3. Much more NADPH than ribose 5-phosphate is required

Much more NADPH than ribose 5-phosphate is required .

For

For

example, adipose tissue requires a high level of NADPH for the synthesis of

example, adipose tissue requires a high level of NADPH for the synthesis of

fatty acids

fatty acids ).

In this case, glucose 6-phosphate is completely oxidized to CO

In this case, glucose 6-phosphate is completely oxidized to CO

22

Three

Three

groups of reactions are active in this situation. First, the oxidative phase of

groups of reactions are active in this situation. First, the oxidative phase of

the pentose phosphate pathway forms two molecules of NADPH and one

the pentose phosphate pathway forms two molecules of NADPH and one

molecule of ribose 5-phosphate. Then, ribose 5-phosphate is converted into

molecule of ribose 5-phosphate. Then, ribose 5-phosphate is converted into

fructose 6-phosphate and glyceraldehyde 3-phosphate by transketolase and

fructose 6-phosphate and glyceraldehyde 3-phosphate by transketolase and

transaldolase. Finally, glucose 6-phosphate is resynthesized from fructose 6-

transaldolase. Finally, glucose 6-phosphate is resynthesized from fructose 6-

phosphate and glyceraldehyde 3-phosphate

phosphate and glyceraldehyde 3-phosphate