pentose phosphate pathway biochemistry topic
- 1. BIOCHEM 700 Pentose Phosphate Pathway
- 2. Pentose Phosphate Pathway • Pentose phosphate pathway (HMP pathway or HMP shunt) is also called as or phosphogluconate pathway. • It is a metabolic pathway in which NADPH and pentoses (5 carbon sugars) ribose 5-phosphate, are generated from glucose 6-phosphate. • The PPP has been demonstrated to be a major regulator for cellular reduction-oxidation (redox) homeostasis and biosynthesis. • This is an alternative pathway to glycolysis and TCA cycle for the oxidation of glucose. • It generates NADPH and pentoses (5-carbon sugars) ribose 5- phosphate, a precursor for the synthesis of nucleotides.
- 3. • It is more anabolic in nature. • 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 enzymes are located in the cytosol. • The tissues such as liver, adipose tissue, adrenal gland, erythrocytes, testes & lactating mammary gland, are highly active in HMP shunt. • Most of these tissues are involved in biosynthesis of fatty acids and steroids which are dependent on the supply of NADPH.
- 5. Significance What is significance of pentose phosphate pathway? 1. Generation of 5 C pentose sugars (a precursor for the synthesis of nucleotides). 2. NADPH(BIOSYNTHETIC PATHWAY) • Fatty acid synthesis • Cholestrol • Detoxification
- 6. Reactions of the Pathway Reactions of the pathway are divided into two phases • oxidative Phase • Non – oxidative Phase
- 7. Oxidative Phase of Pentose Phosphate Pathway • The oxidative phase of the pentose phosphate pathway oxidizes a glucose 6-phosphate into a ribose 5-phosphate while in the process generated two NADPH molecules, a carbon dioxide and 2 H+ ions.
- 8. Regulatory enzyme Ribose -5-Phosphate Phosphopentose isomerase
- 9. Non-Oxidative Phase of Pentose Phosphate Pathway • The nonoxidative reactions of the pentose phosphate pathway occur in all cell types synthesizing nucleotides and nucleic acids. • These reactions catalyze the interconversion of three-, four-, five-, six-, and seven-carbon sugars. • The non-oxidative phase links the glycolytic pathway to the pentose phosphate pathway • It allows our cells a way to break down ribose molecules ingested into our body.
- 10. Non oxidative phase Fructose 6- Phosphate, GA-3-P
- 11. What is net reaction of non oxidative phase?
- 14. REGULATION OF PENTOSE PHOSPHATE PATHWAY What is rate limiting step of pentose phosphate pathway. Step 1 of oxidative phase • Conversion of Glucose 6-phosphate to 6- phosphogluconolactone by the help of enzyme glucose 6 phosphate dehydrogenase. • The enzyme of this step is allosterically stimulated by NADP+ and inhibited by NADPH. • Insulin enhances G6PD gene expression, and flux through the pathway increases in the well fed state.
- 15. • The entry of glucose 6-Phosphate into Pentose phosphate pathway is controlled by cellular concentration of NADPH. • So the oxidative phase is controlled by NADPH. • The non oxidative phase is controlled by pentoses.
- 16. CLASS ACTIVITIES 1. What are Bioenergetics of the pathways? No ATP is directly consumed or produced in this pathway. 2. In which tissue pentose phosphate pathway is less active? In muscles due to small amount of dehydrogenase enzyme. 3. A 50 years old alcoholic male was diagnosed with thiamine deficiency, which enzyme would become inactive in this individual? 4. The oxidation of 3 molecules of glucose by pentose phosphate pathway generates how many fructose 6-phosphates? 5. Which phase of Pentose phosphate pathway is reversible and which is irreversible? 6. What is NADH and NADPH? 7. Which carbon of glucose 6 phosphate is released as CO2 in oxidative phase?
- 17. CLASS ACTIVITY: WHY IS HMP KNOWN AS SHUNT.? • CLASS ACTIVITY: What are pentoses? Why do we need them?
- 18. Suggested Readings • Ferrier, D. R. 2013. Biochemistry: Lippincott's Illustrated Reviews. 6th ed. Lippincott Williams and Wilkins. U.S.A. • Nelson DL and Cox MM. Lehninger Principles of Biochemistry. Fourth Edition. • Berg JM et al. (2012) Biochemistry. Seventh Edition. W. H Freeman and Company.