PPP PATHWAY

1. HMP PATHWAY
PENTOSE PHOSPHATE
PATHWAY

2. HMP Pathway
Also known as phosphogluconate oxidative pathway,
pentose phosphate pathway, shunt pathway or Dickens-
Horecker pathway.
Glucose is shunted through this pathway instead of
glycolysis.
Alternate pathway for glucose metabolism, 10% of
glucose molecules per day enter this pathway.

3. HMP PATHWAY
 Active in lactating mammary gland, liver,
RBC, adrenal cortex, adipose tissue and
thyroid gland
 NADP+ and not NAD+ is used as hydrogen
acceptor

4. 30% Glucose Oxidised Via
HMP in Liver and RBC

5. HMP Pathway
Ribose
NADPH
Reductive
biosynthesis

6.  Two phases in the pathway
(i) Oxidative irreversible phase
(ii) Non oxidative reversible phase
 Pathway generates NADPH (for reductive
synthesis of substances) and ribose sugar
(for nucleic acid synthesis)

8. `

9. Tissues
The non oxidative phase is present in all tissues, and so
ribose synthesis is possible in all tissues in the body.
Oxidative phase is seen in organs where fatty acid or
steroid biosynthesis occurs.
It also has an important role in the lens of the eye and
RBC’s.

10. IMPORTANCE OF NADPH
 Reductive synthesis of compounds (H2 donor)
 Fatty acids
 Steroid hormones
 Cholesterol
 Amino acids

11.  Conversion of methaemoglobin to
haemoglobin
Methemoglobin Haemoglobin
NADPH + H+ NADP+
Methemoglobin
reductase

12.  Activity of microsomal cyt P450 system
RH (Steroids, Alcohols, drugs)
NADPH +H+ Microsomal cyt P450 monoxygenase
system
O2
H2O
NADP+
R – OH
Cytochrome P450

13.  Synthesis of reduced glutathione
GSSG (Oxi) 2GSH (red)
NADPH + H+ NADP+
Glutathione reductase

14. Glutathione in RBC’s

15. NADPH Is Essential to
Maintain RBC Membrane
Integrity
The PPP supplies the RBC with NADPH to maintain the
reduced state of glutathione.
The inability to maintain reduced glutathione in RBCs leads to
increased accumulation of peroxides, predominantly H2O2,
that in turn results in a weakening of the cell wall and
concomitant hemolysis.
Accumulation of H2O2 also leads to increased rates of
oxidation of hemoglobin to methemoglobin that also weakens
the cell wall.

16. 6. ROLE OF NADPH IN PHAGOCYTOSIS
O2
NADPH RESPIRATORY BURST
NADP +
O2
*
H2O2
Cl - Fe 2+
Fe 3+ Bacterium
HOCl• OH-
Bacterium
Neutrophil phagocytosis – O2 dependent mechanism
NADPH oxidase
Superoxide dismutase
Myeloperoxidase

17. Other Functions
NADPH is essential for maintaining the transparency of
the lens.
NADPH is essential for the production of superoxide
anion radical by the macrophages in response to
bacteria.
Ribose and deoxyribose are essential for the synthesis of
nucleic acids and nucleotides.

18. Clinical Significance &
disorders of HMP pathway
1.Glucose 6 phosphate
deficiency:
Most common enzyme
deficiency seen in clinical
setting.
X linked inheritance
Drug induced hemolytic
anemia.

19.  Manifested as RBC hemolysis, when the
susceptible individual is subjected to
– Oxidants
– Antimalarials (primaquine)
– Aspirin
– Sulphonamides
Advantage: The absence of the enzyme offers
resistance to malaria.

20. Contd..
2. Methemoglobinemia:
Increased met-hemoglobin in circulation
3. Thiamine deficiency:
The transketolase reaction is measured in
RBC’s as an index of thiamine status of an
individual.