Hexose Monophosphate Shunt Pathway - HMP Pathway

1. HMP Pathway
Dr. M. N. Astagimath, M.D.

2. Hexose Monophosphate
Shunt
• Synonyms
– Phosphogluconate Oxidative Pathway
– Pentose Phosphate pathway
– Direct Oxidative Pathway for Glucose
– Dickens – Horecker Pathway
• It is an alternate pathway for Glucose. An
aerobic pathway in which 3 molecules of
glucose 6-phosphate give rise to three
molecules of CO2 and three five-carbon
sugars. .

3. •Intracellular site - Cytosol
Tissues
Liver
Adipose Tissue
Adrenal Cortex
Testis
Ovary
Lactating
Mammary Gland
RBCs
Neutrophils
10% of glucose molecules per day are entering this
pathway
The liver and RBC Metabolise 30% of glucose by
this pathway.

4. Functions / Significance

5. Overview
• Has two phases – Oxidative and Non
Oxidative

21. Regulation of the Pentose
Pathway
• Glucose 6-phosphate DH is the
regulatory enzyme.
• NADPH is a potent competitive
inhibitor of the enzyme.
• Usually the ratio NADPH/NADP+ is
high so the enzyme is inhibited.
• But, with increased demand for
NADPH, the ratio decreases and
enzyme activity is stimulated.

22. • The reactions of the non-oxidative
portion of the pentose pathway are
readily reversible.
• The concentrations of the products
and reactants can shift depending on
the metabolic needs of a particular
cell or tissue.

23. Rapidly dividing cells require more ribose 5-
phosphate than NADPH.
Glycolysis converts G6P to F6P and GAP which are used by the
PPP to produce ribose 5- phosphate.

24. The need for NADPH and ribose 5-phosphate is
balanced
PPP converts G6P to R5P producing 2 NADH molecules.

25. More NADPH is needed than ribose 5-
phosphate; Fatty acid synthesis in adipose cells.
G6P is oxidatively
decarboxylated via PPP to
produce CO2 forming 2
NADPH. R5P is then converted
to F6P and GAP.
Through the gluconeogenic
pathway, F6P and GAP form
G6P. G6P undergoes
decarboxylation again to
produce more NADPH.

26. The cell needs both NADPH and ATP
G6P can undergo the
oxidative phase of
PPP to yield NADPH. In
the non-oxidative phase
of PPP, the resulting R5P
forms F6P and GAP which
enter glycolysis to
eventually form pyruvate.
Pyruvate then continues
on to oxidative
phosphorylation to
produce ATP.

31. Uronic Acid Pathway
• It is an alternative oxidative pathway for
glucose that, like the pentose phosphate
pathway, does not lead to generation of
ATP
• It includes oxidation of glucose to
1. Glucuronic acid: which is used in detoxication
and enters in the formation of
ucopolysaccharide.
2. Ascorbic acid
• It mainly occurs in liver cytoplasm,

32. Formation of UDP-glucuronic
acid
• Glucose 6-phosphate is isomerized to
glucose 1-phosphate, which then reacts
with uridine triphosphate (UTP) to form
uridine diphosphate glucose (UDPGlc) in a
reaction catalyzed by UDPGlc
pyrophosphorylase
• UDPGlc is oxidized at carbon 6 by NAD-
dependent UDPGlc dehydrogenase in a
two-step reaction to yield UDP-glucuronate

33. Formation of UDP-glucuronic
acid

34. Importance of UDP-Glucuronic
acid
• UDP Glucuronic acid (active form) is needed in:
– conjugation to less polar compounds as bilirubin,
steroids and some drugs making them more water soluble
(detoxicated)
– synthesis of glycosaminoglycans (mucopolysaccharide)
as heparin, hyaluronic acid…
– In plants and some animals (not Human) glucuronic acid
serves as a precursor of L-ascorbic acid
– The uronic acid pathway also provides a mechanism by
which dietary D-xylulose enter the central pathway