Pentose phosphate pathway/ Hexose monophosphate shunt
By Dr. Atirah Tauseef
2026
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.
, Oxidative Phase: The oxidative phase of the pentose phosphate pathway is composed of three steps.
Step 1
2- + + 2-
CH 2OPO3 NADP NADPH + H CH2OPO3
O
Glucose-6-phosphate dehydrogenase
H OH H OH
6-Phosphogluconolactone
Step 2:
O
2- -
CH2OPO3 H2O
+
H C O
H O
H C OH
OH H O HO C H
OH Glucolactonase H C OH
H OH H C OH
2-
CH2OPO3
6-Phosphogluconolactone
6-Phosphogluconate
Step-3
O O
-
C O NADP
+
NADPH + H
+ C O-
H C OH H C OH
HO C H C O
H C OH H C OH
6-Phosphogluconate
H C OH dehydrogenase H C OH
CH OPO 2- CH OPO 2-
2 3 2 3
6-Phosphogluconate
H+
CO2
CH2OH
H+
C O
H C OH H C OH
H C OH
C O-
CH OPO 2- H C OH
2 3
Ribulose-5-phosphate H C OH
2-
CH2OPO3
By Dr. Atirah Tauseef
2026
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.
, Oxidative Phase: The oxidative phase of the pentose phosphate pathway is composed of three steps.
Step 1
2- + + 2-
CH 2OPO3 NADP NADPH + H CH2OPO3
O
Glucose-6-phosphate dehydrogenase
H OH H OH
6-Phosphogluconolactone
Step 2:
O
2- -
CH2OPO3 H2O
+
H C O
H O
H C OH
OH H O HO C H
OH Glucolactonase H C OH
H OH H C OH
2-
CH2OPO3
6-Phosphogluconolactone
6-Phosphogluconate
Step-3
O O
-
C O NADP
+
NADPH + H
+ C O-
H C OH H C OH
HO C H C O
H C OH H C OH
6-Phosphogluconate
H C OH dehydrogenase H C OH
CH OPO 2- CH OPO 2-
2 3 2 3
6-Phosphogluconate
H+
CO2
CH2OH
H+
C O
H C OH H C OH
H C OH
C O-
CH OPO 2- H C OH
2 3
Ribulose-5-phosphate H C OH
2-
CH2OPO3
