Pentose Phosphate Pathway - Biochemistry - Lecture Notes, Study notes of Biochemistry

Pentose Phosphate Pathway, Oxidative Phase, Nonoxidative Phase, First Step of the Phosphopentose, Course Allosterically Regulated, Strong Inhibitor, Pentose Phosphate Pathway, Series of Reactions, two Molecules of Hexoses and One Triose, Tissues Less Active in Fatty Acid Synthesis are few points from this lecture notes. If you are looking for complete set of lectures on biochemistry, you can find it in my documents section.

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Pentose Phosphate Pathway
Aka the Hexose Monophosphate Shunt
In most animal tissues, glucose is catabolized via the glycolytic pathway into two molecules of pyruvate.
Pyruvate is then oxidized via the citric acid cycle to generate ATP. There is another metabolic fate for
glucose used to generate NADPH and specialized products needed by the cell. This pathway is called the
pentose phosphate pathway. Some text books call it the hexose monophosphate shunt, still others call it
the phosphogluconate pathway. We will call it in this class the pentose phosphate pathway.
The pentose phosphate pathway produces NADPH which is the universal reductant in anabolic pathways. In
mammals the tissues requiring large amounts of NADPH produced by this pathway are the tissues that
synthesize fatty acids and steroids such as the mammary glands, adipose tissue, adrenal cortex and the liver.
Tissues less active in fatty acid synthesis such as skeletal muscle are virtually lacking the pentose phosphate
pathway.
The second function of the pentose phosphate pathway is to generate pentoses, particularly ribose which is
necessary for the synthesis of nucleic acids.
It is convenient to think of the pentose phosphate
pathway as operating in two phases. The first
phase is the oxidative phase. Two of the first
three reactions of the first phase generate
NADPH. The second phase is the nonoxidative
phase.
In the first step glucose-6-phosphate is oxidized
into ribulose-5-phosphate, CO2. During the
oxidation of glucose-6-phosphate NADP+ is
reduced into NADPH.
The second step of the pathway coverts the
ribulose 5-phosphate into other pentose-5-
phosphates including ribose-5-phosphate used to
synthesize nucleic acids.
The third step includes a series of reactions that
convert three of the pentose-5-phosphates into
two molecules of hexoses and one triose.
In the fourth step, some of these sugars are
converted into glucose-6-phosphate so the cycle
can be be repeated. The direction of the pathway
varies to meet different metabolic conditions.
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Pentose Phosphate Pathway

Aka the Hexose Monophosphate Shunt

In most animal tissues, glucose is catabolized via the glycolytic pathway into two molecules of pyruvate.

Pyruvate is then oxidized via the citric acid cycle to generate ATP. There is another metabolic fate for

glucose used to generate NADPH and specialized products needed by the cell. This pathway is called the

pentose phosphate pathway. Some text books call it the hexose monophosphate shunt, still others call it

the phosphogluconate pathway. We will call it in this class the pentose phosphate pathway.

The pentose phosphate pathway produces NADPH which is the universal reductant in anabolic pathways. In

mammals the tissues requiring large amounts of NADPH produced by this pathway are the tissues that

synthesize fatty acids and steroids such as the mammary glands, adipose tissue, adrenal cortex and the liver.

Tissues less active in fatty acid synthesis such as skeletal muscle are virtually lacking the pentose phosphate

pathway.

The second function of the pentose phosphate pathway is to generate pentoses, particularly ribose which is

necessary for the synthesis of nucleic acids.

It is convenient to think of the pentose phosphate

pathway as operating in two phases. The first

phase is the oxidative phase. Two of the first

three reactions of the first phase generate

NADPH. The second phase is the nonoxidative

phase.

In the first step glucose-6-phosphate is oxidized

into ribulose-5-phosphate, CO 2. During the

oxidation of glucose-6-phosphate NADP +^ is

reduced into NADPH.

The second step of the pathway coverts the

ribulose 5-phosphate into other pentose-5-

phosphates including ribose-5-phosphate used to

synthesize nucleic acids.

The third step includes a series of reactions that

convert three of the pentose-5-phosphates into

two molecules of hexoses and one triose.

In the fourth step, some of these sugars are

converted into glucose-6-phosphate so the cycle

can be be repeated. The direction of the pathway

varies to meet different metabolic conditions.

Oxidative Phase : The oxidative phase of the pentose phosphate pathway is composed of three steps.

H^ O
OH
H
OH
H
H OH
OH

CH 2 OPO^ 2- 3 NADP +^ NADPH + H +

H^ O
OH
H
H OH
OH

CH 2 OPO^ 2- (^3)

Glucose-6-phosphate dehydrogenase^ O
6-Phosphogluconolactone

Step 1

H^ O
OH
H
H OH
OH

CH 2 OPO^ 2- (^3)

O

6-Phosphogluconolactone

H 2 O H +

Glucolactonase

O
C O -
H C OH
HO C H
H C OH
H C OH
CH 2 OPO 3 2-
6-Phosphogluconate

Step 2:

O
C O -
H C OH
HO C H
H C OH
H C OH
CH 2 OPO 3 2-

6-Phosphogluconate

NADP +^ NADPH + H +
C OH
C O
H C OH
H C OH
CH 2 OPO 3 2-

Ribulose-5-phosphate

6-Phosphogluconate dehydrogenase

C
H
O
O -
CO 2
C OH
C O -
H C OH
H C OH
CH 2 OPO 3 2-
H
CH 2 OH
C O
H C OH
H C OH
CH 2 OPO 3 2-

H +

H +

Step 3

Transketolase: Requires thiamine pyrophosphate as a cofactor.

N

H 3 C (^) N NH^2

HC (^2) N

C S H

H 3 C H C^2 C H 2 O^ P

O

O -

O P

O

O -

O -

Aminopyramidine
Ring
Thiazolium Ring Pyrophosphate
Thiamine pyrophosphate
Acidic Proton

R N C S

H 3 C R'

C C OH

H H OH

C C OH H C OH H C OH CH 2 OPO^ 2- (^3)

H

O H

B H R^ N C S

H 3 C R'

C C O

H H OH

C C OH H C OH H C OH CH 2 OPO^ 2- (^3)

H

O H

B: H

:B

H

C C OH H C OH H C OH CH 2 OPO (^3)

H

HO H

C C O

H

H OH

R N C S H

H 3 C R'

+ R N

C S

H 3 C R'

  • :

R N C S H

H 3 C R' R N^ + C S

H 3 C R'

  • : C C O

C H

OH C OH

H O 3 POH 2 C

H H OH

H B

R N C S

H 3 C R'

C C OH

C H

O C OH

H O 3 POH 2 C

H H OH

B:

B: H

R N C S

H 3 C R'

C C OH

C H

O

H C^ OH CH 2 OPO (^3)

H H OH

R (^) N C S

H 3 C R'

C C OH

H H OH

  • :

C H

O

H C OH CH 2 OPO 3 2-

C C OH H C OH H C OH CH 2 OPO^ 2- 3

H

HO H

C C O

H

H OH

Glyceraldehyde-3-phosphate
Sedoheptulose-7-phosphate
Step 7: TRANSALDOLASE

C

O

H C OH H C OH CH 2 OPO^ 2- 3

H

erythrose-4P

HO C H

C C O

H

H OH

H C OH H C OH CH 2 OPO 3 2-

Fructose-6P

Transaldolase involves Shiff base formation:

HO C H

C C N

H

H OH Lys

  • :

C O

C H

OH

H -2O 3 POH 2 C

H B

HO C H

C C N

H

H OH Lys

C OH

C H

OH

H -2O 3 POH 2 C

HO C H

C C O

H

H OH

H C OH H C OH CH 2 OPO 3 2- Fructose-6P

H 2 O

C
C OH
H C OH
H C OH
CH 2 OPO^ 2- 3
H
HO H
C
C O
H
H
OH
Lys NH^2
C
C O
H C OH
H C OH
CH 2 OPO^ 2- 3
H
HO H
C
C NH
H
H
OH
  • Lys
H

H 2 O

:B

C
O
H C OH
H C OH
CH 2 OPO^2 - 3
H

Erythrose-4P

HO C H
C
C NH
H
H
OH
Lys
HO C H
C
C N
H
H
OH
Lys
  • :

Putting it all together.

Oxidative phase:

3Glucose-6-phosphate + 6NADP +^  2 Xylulose-5p + ribose-5P + 3CO 2 + 6NADPH + 6H+

Rearrangements of the nonoxidative phase:

2 Xylulose-5P + ribose-5P  2 Frucose-6P + Glyceraldehyde-3P

The sum of these two phases:

3Glucose-6-phosphate + 6NADP +^ 2 Frucose-6P + Glyceraldehyde-3P + 3CO 2 + 6NADPH + 6H +

Tailoring the pentose phosphate pathway to meet specific needs of the cell.

1.) If the cell requires both ribose-5-P and NADPH

Glucose-6-P

6-Phosphogluconate

Ribulose-5-phosphate

Ribose-5-phosphate

NADPH

NADPH + CO (^2)

Both NADPH and Ribose-5P needed.

2.) More ribose-5 phosphate needed than NADPH.

3.) More NADPH needed than Ribose-5-phosphate.