Pentose phosphate pathway

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