The pentose phosphate pathway (PPP; also called the phosphogluconate pathway and the hexose monophosphate shunt) is a process that breaks down glucose-6-phosphate into NADPH and pentoses (5-carbon sugars) for use in downstream biological processes. There are two distinct phases in the pathway: the oxidative phase and the non-oxidative phase.

1. Course Title: Biochemistry III
Prepared By : Rabia Khan Baber

2.  Outline the two major phases of the Pentose Phosphate Pathway:
oxidative and non-oxidative phases
KEY POINTS:
 There are two distinct phases in the pathway: the oxidative phase and
the non-oxidative phase.
 In the oxidative phase, two molecules of NADP+ are reduced to
NADPH, utilizing the energy from the conversion of glucose-6-
phosphate into ribulose-5-phosphate. These NADPH molecules can
then be used as an energy source in elsewhere in the cell.
 The non-oxidative phase generates 5-carbon sugars, which can be used
in the synthesis of nucleotides, nucleic acids, and amino acids.
 The pentose phosphate pathway is an alternative to glycolysis.

3.  Glycolysis: The cellular degradation of the simple sugar
glucose to yield pyruvic acid and ATP as an energy source.
 NADPH: Nicotinamide adenine dinucleotide phosphate
(NADP) carrying electrons and bonded with a hydrogen (H)
ion; the reduced form of NADP+.

4. The pentose phosphate pathway (PPP; also called the
phosphogluconate pathway and the hexose
monophosphate shunt) is a process that breaks down
glucose-6-phosphate into NADPH and pentoses (5-
carbon sugars) for use in downstream biological
processes. There are two distinct phases in the
pathway: the oxidative phase and the non-oxidative
phase.

5.  The Hexose Monophosphate Shunt Pathway is present
in all cells. Mainly the liver, lactating mammary glands,
adipose tissue, adrenal cortex, and red blood cells
(RBCs). Occurs in cell cytoplasm.

8.  The first is the oxidative phase in which glucose-6-
phosphate is converted to ribulose-5-phosphate.
 During this process two molecules of NADP+are reduced to
NADPH. 6-Phosphogluconolactone is hydrolyzed by 6-
phosphogluconolactone hydrolase.
 The oxidative decarboxylation of the product, 6-
phosphogluconate is catalyzed by 6-phosphogluconate
dehydrogenase.
 Pentose sugar–phosphate (ribulose 5-phosphate), CO2 (from
carbon 1 of glucose), and a second molecule of NADPH are
produced.
 Oxidative phase is irreversible phases in pentose phosphate
pathway

11.  Non-oxidative phase is reversible pathway. These reactions catalyze
the interconversion of three-, four-, five-, six-, and seven-carbon
sugars.
 The second phase of this pathway is the non-oxidative synthesis of 5-
carbon sugars.
 Ribulose-5-phosphate can reversibly isomerize to ribose-5-phosphate.
Ribulose-5-phosphate can alternatively undergo a series of
isomerizations as well as transaldolations and transketolations that
result in the production of other pentose phosphates including fructose-
6-phosphate, erythrose-4-phosphate, and glyceraldehyde-3-phosphate
(both intermediates in glycolysis).
 These compounds are used in a variety of different biological
processes including production of nucleotides and nucleic acids
(ribose-5-phosphate), as well as synthesis of aromatic amino acids
(erythrose-4-phosphate).

12. EPIMERIZATION AND ISOMERIZATION
 Epimerase inter-converts
stereoisomers ribulose-5-P
into xylulose-5-P.
 Isomerase converts the
ketose ribulose-5-P to the
aldose ribose

13.  High Activity: Liver, adipose tissue, adrenal cortex,
thyroid, erythrocytes, testis, and lactating mammary
gland.
 These tissues use NADPH in reductive synthesis, eg, of
fatty acids, steroids, amino acids.
 Low Activity: Skeletal muscle, non-lactating mammary
gland.

14.  The Hexose Monophosphate Shunt Pathway provides a
means by which glucose can be oxidized to generate
NADPH and is the source of much of the NADPH that
is needed for the biosynthesis of many biomolecules,
most notably fats.
 The Hexose Monophosphate Shunt Pathway can also
be used for the catabolism of pentose sugars from the
diet, the synthesis of pentose sugars for nucleotide
biosynthesis, and the catabolism and synthesis of less
common four- and seven-carbon sugars.

15.  NADPH produced in the shunt is used for biosynthesis
of several important compounds in various organs.
 In the liver, NADPH is used for fatty acid synthesis,
cholesterol synthesis, bile acid synthesis, glutamate
synthesis and cytochrome P450-hydroxylase system.
 In the adrenal cortex and gonads, NADPH is used for
cholesterol and hormone synthesis.
 In the adipose tissue, NADPH is used for fatty acid
synthesis.
 NADPH is used for the formation of
deoxyribonucleotides and pyrimidine nucleotides.

16.  In RBC, NADPH produced is used for the formation of
reduced glutathione from oxidized glutathione.
Glutathione reductase catalyzes this reaction.
 Reduced glutathione is required for the removal of
H2O2 by glutathione peroxidase for the conversion of
methemoglobin to normal hemoglobin and for
maintenance of –SH groups of erythrocyte proteins.
 So, reduced glutathione is essential for the integrity of
normal red cell structure.
 Usually cells with reduced glutathione levels are more
prone to hemolysis.

17.  Pentoses produced in this pathway are used for nucleic
acid synthesis and nucleotide coenzymes like NAD+,
FAD and FMN synthesis.
 A non-oxidative phase of the pathway converts
pentoses of endogenous or dietary nucleic acids into
intermediates of glycolysis where they are, further
oxidized to generate energy.
 Interconversion of three, four, five, six and seven
carbon sugars in the non-oxidative phase metabolically
connects these sugars to glycolysis

18.  Glucose-6-phosphate dehydrogenase is the rate-
controlling enzyme in this pathway. It is allosterically
stimulated by NADP+. NADPH-utilizing pathways,
such as fatty acid synthesis, generate NADP+, which
stimulates glucose-6-phosphate dehydrogenase to
produce more NADPH. In mammals, the PPP occurs
exclusively in the cytoplasm; it is found to be most
active in the liver, mammary gland, and adrenal cortex.

19.  Textbook of Biochemistry-U Satyanarayana
 Champe, PC, Harvey, RA. 2007. Biochemistry.
Lippincott’s Illustrated Review. 4th Edition. Lippincott
Williams & Wilkins.
 Murray, RK, Bender, DA, Botham, KM, Kennelly, PJ,
Rodwell, VW, Weil, PA. 2006. Harper’s Illustrated
Biochemistry, 28e. Lange, McGraw Hill.