Dr Jaiprakash Mohanraj

PENTOSE PHOSPHATE PATHWAY

 Lecture content for this topic
• Overview
• Phase-1 of the HMP shunt pathway
• Phase-2 of the HMP shunt pathway
• Significance of this pathway
• Regulation of this pathway
 Introduction
• Definition: It is an alternative pathway for the
metabolism of glucose to form pentose sugar.
• The pathway shunts away from glycolytic
pathway, hence also called as Hexose Mono
Phosphate (HMP) Shunt Pathway.
• The pathway requires three glucose to
– remove carbon as CO2 from all the three glucose
– form 3 pentose sugars.
– generate NADPH + H+
• Location: Cytosolic process found in all the tissue
 Reaction of HMP Shunt pathway
• Divided into two phases
1. Oxidative irreversible phase
2. Nonoxidative reversible phase
 Phase 1 reaction of HMP Shunt
pathway
Glucose Glucose Glucose

G-6-P G-6-P G-6-P

G6P NADP NADP NADP

Dehydrogenase NADPH + H+ NADPH + H+ NADPH + H+
6 Phospho 6 Phospho 6 Phospho
gluconolactone gluconolactone gluconolactone
Hydrolase

6 Phosphogluconate 6 Phosphogluconate 6 Phosphogluconate

NADP NADP NADP
6 Phosphogluconate
Dehydrogenase

CO2 NADPH + H+ CO2 NADPH + H+ CO2 NADPH + H+

Ribulose-5-P Ribulose-5-P Ribulose-5-P
Phase 2 Reaction of HMP Shunt Pathway
Ribulose-5-P Ribulose-5-P Ribulose-5-P

Xylulose-5-P Ribulose-5-P Xylulose-5-P

Transketolase TPP

Glyceraldehy-3-P Sedoheptulose-7-P

Transaldolase

Fructose-6-P Erythrose-4-P
.
Transketolase TPP

Fructose 6 P Glyceraldehyde 3 P

Glucose-6-P Glucose-6-P
Glucose-6-P ½ Glucose-6-P
 Significance
• Synthesis of NADPH
– Fatty acid synthesis
– Cholesterol synthesis
– Deoxyribonucleic acid synthesis
– Reduction of glutathione
– Detoxification
• Generation of Pentoses
– Synthesis of nucleotides
Regulation of HMP shunt pathway
• G-6-P dehydrogenase (G6PD) is the rate
limiting enzyme that is regulated
• Intracellular concentration of NADPH
• Disorders of HMP shunt pathway
– G6PD deficiency
• Genetic disorder
 Pathway Significance Substrates involved Enzymes Location
regulated
Glycolytic Energy pro (8) Glu, G6P, F6P, F1,6BP, G6P Kinase Cytosolic
pathway (10 Precursors DHAP, G3P, G1,3BP, PFK,
steps) 3PG, 2PG, PEP, P PK
RL cycle (2) RBC 1,3 BPG, 2,3 BPG Mutase, Cytosolic
Phosphatase
TCA (8) Energy(24), ACoA, Cit, IsC, KG, CS, IsC dehy, Mito
Anaplerosis SCoA, Su, Fu, Ma KG dehy
Gluconeogensis Prod of Glu Pyr, OA, Mal, OA, Pyr Cabo, PEP Liver (cyto +
(6) PEP,…F1,6BP, G6P CK, F1,6 Mito)
BPase, G6Pase
Glycogenesis (5) Synth of Gly G6P, G1P, UDP-G, Gly Syn Cyosolic
1,4Gl, Glyco (Liv. + Ms.)
Glycogenolysis (3) Lysis of Gly Gly, G1P, G6P Gly Phop Cytosolic
HMP shunt Prod of Pento G6P, 6PGL, 6PG, G6P dehy, Cytosolic
Prod of NADH Ru5P, X5P, Gly3P, S7P, 6PGL dehy, TK,
F6P, E4P, G6P TA