Download Hexose Monophosphate Shunt (HMP Shunt)

Hexose Monophosphate Shunt
(HMP Shunt)
Learning objectives

To explain HMP shunt

To underline the significance of HMP shunt

To compare the features of HMP shunt & glycolysis

To describe the process (reactions) of HMP shunt

To explain the regulation of HMP shunt
Hexose Monophosphate Shunt
(HMP Shunt)
Also knows as
“Pentose Phosphate Pathway (PPP)”
“Pentose Cycle”
“Phosphogluconate Pathway”
Occurrence of HMP Shunt
HMP shunt is active in

Liver, lactating mammary glands, thyroid, adipose tissue,
leukocytes, RBCs, testes and adrenal cortex
HMP shunt (PPP) is less active in skeletal muscle &
non-lactating mammary glands
Site:-
Cytosol
Biomedical Importance


Alternate pathway for oxidation of Glucose, with no ATP
production, but has two major functions;

Provides NADPH, required for reductive syntheses and
some other reactions

Provides pentoses, required for Nucleic Acids and
Nucleotide synthesis
Deficiency of certain enzymes leads to hemolytic anemia.
e.g. G6P Dase (G-6-P
dehydrogenase )
Comparison of HMP Shunt & Glycolysis
S.No.
HMP Shunt
Glycolysis
1
Occurs in specialized tissues
Occurs in all tissues
2
Site is Cytosol
Site is Cytosol
3
Multi-cyclic Process
Not a Multi-cyclic process
4
NADP used as Co-enzyme
NAD used as Co-enzyme
Comparison of HMP Shunt & Glycolysis
S.No.
HMP Shunt
Glycolysis
5
ATP required initially
ATP required initially
6
ATPs not produced
ATPs produced
7
CO2 is formed during
HMP shunt
No CO2 is formed during
glycolysis
8
Pentoses are generated
No pentose is generated
9
Only monophosphate
intermediates
Diphosphate intermediates
are also involved
Overall Reaction
6NADP+
6NADPH + H+
2 Glc–6–P + 3CO2 + Glyceraldehyde–3–P
3 Glc – 6 – P
3CO2
3 Glc
3 Pentoses
2 Glc + 1 Triose
6 Pentoses
5 Glc
6CO2
Or
6 Glc
Phases of HMP Shunt
Two Phases
1. Oxidative Phase
Dehydrogenation and decarboxylation of
Glucose-6-P to form pentose phosphates.
(Enzymes – Dehydrogenases)
2. Non-Oxidative Phase
Conversion of pentose phosphates to Glucose-6-P
through a series of reactions
(Enzymes – Transaldolase and Transketolase)
Reactions of HMP Shunt
Reactions of HMP Shunt
Enediol
Ribulose-5-P
Reactions of
HMP Shunt
(Contd.)
TPP
Nucleotides
& Nucleic acids
Oxidative stage of Pentose Phosphate Pathway
Non-oxidative reactions of PPP
Reactions of
HMP Shunt
(Contd.)
Regulation of HMP Shunt

Rate limiting enzyme is G-6-Pdase & the other dehydrogenase

NADPH / NADP ratio

NADPH inhibits both dehydrogenases

Activity of dehydrogenases decreases in
 Diabetes mellitus and
 Starvation
Regulation of HMP Shunt

Insulin (fed state) induces the synthesis of key enzymes
(G6Pdase & 6-P-Gluconate-DH)

Activity of these enzymes also increases in lipogenesis
(fatty acid & steroid synthesis)

Thyroid hormones also lead to increased activity of the
dehydrogenases  increased HMP Shunt
Functions of NADPH
NADPH is required for
1. Synthesis of fatty acids
2. Synthesis of Cholesterol (steroids)
3. Synthesis of Glutamate from -ketoglutarate
4. Synthesis of Tyrosine from phenylalanine
5. Synthesis of Gulonic acid from glucuronic acid
(Uronic acid pathway)
6. Synthesis of tetra-hydro-folate(FH4)
7. Conversion of oxidized glutathione to reduced glutathione
(G–S–S–G)
(2G – SH)
Role of Glutathione

H2O2 increases the rate of oxidation of hemoglobin to
methemoglobin and damages the cell membrane 
leading to hemolysis

Glutathione degrades (detoxifies) the free radicals and
hydroperoxides produced in oxygen rich environments
like RBCs
Role of Glutathione
H2O2
Glutathione
(GSH)
2H2O
Glutathione Peroxidase
NADPH + H+
Glutathione disulfide
(GSSG)
NADP+
GSSG
2GSH
Glutathione Reductase
G-6-Pdase Deficiency

Oxidant drugs which may cause drug-induced
hemolysis in G-6-Pdase deficient subjects include:
1.
Antimalarials (Primaquin & Pamaquin)
2.
Analgesics (Acetyl salicylic acid, Phenacetin)
3.
Sulfonamides
4.
Furadentin & furoxone & many others