Hexose monophosphate pathway (HMP)
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The document summarizes the hexose monophosphate pathway (HMP pathway), also known as the pentose phosphate pathway. It has two phases - an oxidative phase that generates NADPH, and a non-oxidative phase that converts pentoses to hexoses. The pathway takes place in the cytosol and is important in the liver, red blood cells, and other tissues for generating NADPH for biosynthesis of fatty acids and steroids. It involves the oxidation of glucose-6-phosphate through a series of steps to ultimately regenerate glucose-6-phosphate while producing NADPH and pentose sugars.
Hexose monophosphate pathway (HMP)
- 1. Hexose monophosphate pathway (HMP) Dr. Aswartha Harinath Reddy Department of Life Sciences Srikrishnadevaraya University Anantapur –A.P. India
- 2. HMP shunt pathway also known as pentose phosphate pathway or phosphogluconate pathway or Warburg–Dicken- Lipman pathway is a metabolic pathway parallel or alternative to glycolysis. In Hexose monophosphate pathway in which oxidation of glucose 6-phosphate takes place to produce pentoses. It generates NADPH and pentoses (5-carbon sugars) as well as ribose 5-phosphate, a precursor for the synthesis of nucleotides.
- 3. It involve oxidation of glucose, About 10% of glucose entering in this pathway/day. The liver & RBC metabolise about 30% of glucose by this pathway.
- 4. Location of the pathway: The pathway located in the cytosol of the cells. The tissues such as liver, adipose tissue, adrenal gland, erythrocytes are highly active in HMP. Most of these tissues are involved in biosynthesis of fatty acids and steroids which are dependent on the supply of NADPH. This NADPH is supplied by HMP.
- 5. The HMP pathway starts with glucose 6-phosphate. No ATP is directly utilized or produced in HMP shunt. There are two distinct phases in the pathway. The first is the oxidative phase, in which NADPH is generated, and the second is the conversion of Pentoses into Hexoses (Non oxidative phase).
- 6. Oxidative phase: Step1: Oxidation of Glucose 6 phosphate to 6-phosphogluconolactone: This phase starts with the oxidation of 6 molecules glucose 6- phosphate by the enzyme glucose 6-phosphate dehydrogenase to yield 6-phosphogluconolactone. This enzyme is an NADP dependent enzyme, where NADP+ reduced to NADPH + H+.
- 7. Step 2: Hydrolysis The 6-phosphogluconolactone is unstable it hydrolysis to 6- phosphogluconic acid. The enzyme catalyze the reaction is gluconolactonase.
- 8. Step 3: Oxidation and decarboxylation: The 6-Phosphogluconic acid is oxidatively decarboxylated by the enzyme 6-Phosphogluconic acid dehydrogenase. The 6 molecules of NADP are reduced to NADPH, 6 molecules of CO2 are released and 6 molecules, of Ribulose- 5-Phosphate are produced.
- 9. Non oxidative phase: Step 4: Isomerization and Epimerization of Ribulose 5-phosphate: The 6 molecules of Ribulose-5-P isomerise into 4 molecules of Xyluose-5- Phosphate and 2 molecules of Ribose-5-Phosphate in the presence of Ribulose phosphate-5-epimerase and Pentose phosphate isomerase respectively. Epimer Isomer 5
- 10. Step 5: 2 mols. of xylulose-5-Phosphate and 2 mols. of Ribose-5- phosphate combine in the presence of Transketolase to form 2 mols. of Sedoheptulose-7-Phosphate and 2 mols. of 3- Phosphoglyceraldehyde.
- 11. Step 6: 2 mols. of Sedoheptulose-7-Phosphate and 2 mols. of 3- Phosphoglyceraldehyde combine in the presence of Transaldolase to form 2 mols. of Fructose-6-Phosphate and 2 mols. of Erythrose-4-Phosphate (4-carbon atoms sugar).
- 12. Step 7: 2 mols. of Erythose-4-Phosphate react with remaining two mols. of xylulose-5-Phosphate (see reaction No. 4 and 5) in the presence of Transketolase to form 2 mols. of Fructose- 6-Phosphate and 2 mols of 3-Phosphoglyceraldehyde. 3 2
- 13. Step:8 One mol. of 3-phosphoglyceraldehyde isomerises into dihydroxyacetone phosphate. In the presence of enzyme Phosphotriose isomerase.
- 14. Step 9: Remaining one mole, of 3-Phosphoglyceraldehyde unites with Dihydroxyacetone phosphate in presence of Aldolase to form one mol. of Fructose 1, 6-bisphosphate. The latter, in the presence of Phosphatase one mol. of Fructose 1, 6-bisphosphate forms one mol. of Fructose 6- Phosphate.
- 15. Step 9
- 16. Step 10: Isomerisation: 5 molecules of Fructose-6-phosphate produced in reactions 6, 7 and 9, isomerise into 5 mols. of Glucose-6-P in presence of Phosphohexose isomerase.
- 18. Significance of HMP Shunt: Producing NADPH : Hexose Mono-Phosphate Shunt producing Biochemical reductant NADPH. This reductant participating in Fatty acid Biosynthesis. NADPH is co-factor for Glutathione Reductase. This enzyme neutralizes the superoxide and hydroxyl radicals from hydroxyl peroxide molecules.
- 19. Producing Ribose-5-Phosphate: Hexose MonoPhosphate shunt provides Ribose-5-Phosphate for the Purine biosynthesis. Producing Glycolytic Intermediate: In the Hexose MonoPhosphate Shunt Pathway, few molecules of Glycolytic intermediates are produced these are directly involves in Glycolysis. The molecules are Glyceraldehyde-3-Phosphate and Fructose-6- Phosphate.