The document summarizes the pentose phosphate pathway. It consists of an oxidative phase and a non-oxidative phase. The oxidative phase generates NADPH and ribulose 5-phosphate through oxidation reactions. The non-oxidative phase converts ribulose 5-phosphate into other 5-carbon sugars, regenerating glucose 6-phosphate while producing ribose 5-phosphate. The pathway provides reducing power in the form of NADPH for biosynthesis and maintains levels of the antioxidant glutathione.

1. PENTOSE PHOSPHATE PATHWAY
NILOUFER M.A and Dr. KAYEEN VADAKKAN
DEPARTMENT OF BIOTECHNOLOGY
ST.MARY’S COLLEGE, THRISSUR

2. PENTOSE PHOSPHATE PATHWAY, NILOUFER M.A, ST.MAR’YS COLLEGE - THRISSUR
INTRODUCTION
•Also known as Hexose Monophosphate (HMP)shunt.
•Alternative route for the metabolism of glucose.
• More complex pathway than glycolysis.
•It helps in-
 Formation of NADPH for synthesis of fatty acids ,steroids.
 Maintaining reduced glutathione for antioxidant activity.
 Synthesis of ribose for nucleotide and nucleic acid formation.

3. PENTOSE PHOSPHATE PATHWAY, NILOUFER M.A, ST.MAR’YS COLLEGE - THRISSUR
PENTOSE PHOSPHATE PATHWAY
• Like glycolysis it occurs in cytosol.
• Oxidation is achieved by dehydrogenation using NADP+ , not NAD+
Its carried out in 2 step;
>Irreversible oxidative phase: 3 molecules of glucose-6-phosphate
give rise to 3 molecules of co
2
and 3 5-carbon sugars.
>Reversible non-oxidative phase: Rearranged to regenerate
2 molecules of glucose-6-phosphate and 1 molecule of
glyceraldehyde-3-phosphate.

4. PENTOSE PHOSPHATE PATHWAY, NILOUFER M.A, ST.MAR’YS COLLEGE - THRISSUR
OXIDATIVE PHASE
In this phase, two molecules of NADP+ are reduced to NADPH, utilizing
the energy from the conversion of glucose-6-phosphate into ribulose-5-
phosphate.
• Dehydrogenation of glucose-6-phosphate to 6-phosphogluconolactone
catalyzed by glucose-6-phosphate dehydrogenase.
• Followed by hydrolysis of 6-phosphogluconolactone to
6-phosphogluconate by enzyme lactonase.

5. PENTOSE PHOSPHATE PATHWAY, NILOUFER M.A, ST.MAR’YS COLLEGE - THRISSUR
•Decarboxylation follows with the conversion of 6-
phosphogluconate into the ketopentose
ribulose-5-phosphate.
Overall equation is,
Glucose 6-phosphate + 2 NADP+ + H2O → ribulose 5-
phosphate + 2 NADPH + 2 H+ + CO2
•The net result is the production of NADPH , a reductant for
biosynthetic reactions, and ribose-5-phosphate,a precursor
for nucleotide synthesis.

6. PENTOSE PHOSPHATE PATHWAY, NILOUFER M.A, ST.MAR’YS COLLEGE - THRISSUR
NON-OXIDATIVE PHASE
•Ribulose-5-phosphate is the substrate for two enzymes;
 Ribose-5-phosphate ketoisomerase:ribulose-5-phosphate to
the corresponding ribose-5-phosphate ,used for nucleotide and
nucleic acid synthesis.
 Ribulose-5-phosphate 3-epimerase:alters the configuration about
carbon giving xylulose-5-phosphate.
•Xylulose-5-phosphate (5c) and ribose-5-phosphate(5c) reacts to give
glyceraldehydes-3-phosphate (3c) and sedoheptulose-7-phosphate(7c)
by the enzyme Transketolase.
•Glyceraldehyde-3-phosphate (3c) and sedoheptulose-7-phosphate(7c)
is acted by Transaldolase to give fructose-6-phosphate and erythrose-
4-phosphate.

7. PENTOSE PHOSPHATE PATHWAY, NILOUFER M.A, ST.MAR’YS COLLEGE - THRISSUR
•Erythrose-4-phosphate and xylulose-5-phosphate reacts in the
presence of enzyme transketolase to give fructose-6-phosphate and
glyceraldehyde-3-phosphate.
Mg2+ and thiamin diphosphate (vitaminB1) as coenzyme
• Subsequently fructose-6-phosphate is isomerised to
glucose-6-phosphate by enzyme phosphohexose isomerase.
Net reaction:
3 ribulose-5-phosphate → 1 ribose-5-phosphate + 2 xylulose-5-
phosphate → 2 fructose-6-phosphate + glyceraldehyde-3-
phosphate
•A genetic defect in transketolase that lowers its affinity for TPP
exacerbates the Wernicke-Korsakoff syndrome.

8. PENTOSE PHOSPHATE PATHWAY, NILOUFER M.A, ST.MAR’YS COLLEGE - THRISSUR
OXIDATIVE PHASE
NON-OXIDATIVE PHASE

9. PENTOSE PHOSPHATE PATHWAY, NILOUFER M.A, ST.MAR’YS COLLEGE - THRISSUR
•Entry of glucose-6-phosphate either into glycolysis or into the pentose
phosphate pathway is largely determined by the relative concentration of
NADP+ and NADPH.
Regulation
• Glucose-6-phosphate dehydrogenase is the rate-controlling enzyme of
this pathway.
• It is allosterically stimulated by NADP+ and strongly inhibited by NADPH.
• The ratio of NADPH:NADP+ is normally about 100:1 in liver cytosol. This
makes the cytosol a highly-reducing environment.
• An NADPH-utilizing pathway forms NADP+, which stimulates Glucose-6-
phosphate dehydrogenase to produce more NADPH.
• This step is also inhibited by acetyl CoA

10. PENTOSE PHOSPHATE PATHWAY, NILOUFER M.A, ST.MAR’YS COLLEGE - THRISSUR
Reactants Products Enzyme Description
Glucose 6-phosphate+
NADP+
→ 6-phosphoglucono-δ-
lactone + NADPH
glucose 6-phosphate
dehydrogenase
Dehydrogenation. The
hydroxyl on carbon 1 of
glucose 6-phosphate turns
into a carbonyl, generating
a lactone, and, in the
process, NADPH is
generated.
6-phosphoglucono-δ-
lactone + H2O
→ 6-phosphogluconate +
H+
6-
phosphogluconolactonase
Hydrolysis
6-phosphogluconate +
NADP+
→ ribulose 5-
phosphate + NADPH + CO2
6-phosphogluconate
dehydrogenase
Oxidative decarboxylation.
NADP+ is the electron
acceptor, generating
another molecule
of NADPH, a CO2,
and ribulose 5-phosphate.
:
The entire set of reactions of oxidative phase can be summarized as
follows:

11. PENTOSE PHOSPHATE PATHWAY, NILOUFER M.A, ST.MAR’YS COLLEGE - THRISSUR
The entire set of reactions of non-oxidative phase can be summarized
as follows:
Reactants Products Enzymes
Ribulose-5-phosphate → ribose 5-phosphate Ribose-5-phosphate isomerase
Ribulose-5-phosphate → xylulose-5-phosphate
Ribulose-5-Phosphate 3-
Epimerase
Xylulose-5-
phosphatate + ribose 5-
phosphate
→ glyceraldehyde-3-
phosphate + sedoheptulose-7-
phosphate
Transketolase
Sedoheptulose-7-
phosphate + glyceraldehyde-3-
phosphate
→ erythrose-4-
phosphate + fructose 6-
phosphate
Transaldolase
Xylulose-5-
phosphate+ erythrose-4-
phosphate
→ glyceraldehyde-3-
phosphate+ fructose 6-
phosphate
Transketolase

12. PENTOSE PHOSPHATE PATHWAY, NILOUFER M.A, ST.MAR’YS COLLEGE - THRISSUR

13. PENTOSE PHOSPHATE PATHWAY, NILOUFER M.A, ST.MAR’YS COLLEGE - THRISSUR
IMPORTANCE OF NADPH
• Bio-synthesis of fatty acid.
• Certain aminoacid involving the enzyme glutamate dehydrogenase.
• Antioxidant reaction-Glutathione mediated reaction of H2O2.
• Detoxification of drugs-cytochrome P450.
• Phagocytosis.
• Integrity of RBC membrane.

14. PENTOSE PHOSPHATE PATHWAY, NILOUFER M.A, ST.MAR’YS COLLEGE - THRISSUR
OUTCOME
The primary results of the pathway are:
• The generation of reducing equivalents, in the form of
NADPH, used in reductive biosynthesis reactions within
cells (e.g. fatty acid synthesis).
• Production of ribose 5-phosphate(R5P), used in the
synthesis of nucleotides and nucleic acids.
• Production of erythrose 4-phosphate (E4P) used in the
synthesis of aromatic amino acids.

15. PENTOSE PHOSPHATE PATHWAY, NILOUFER M.A, ST.MAR’YS COLLEGE - THRISSUR