![Regulation of HMP shunt
• Occurs in 3 ways:
• 1. Ratio of [NADP]/[NADPH] ,
• G6PDH is rate limiting enzyme , it require
NADP hence increase level of NADPH
decreases reaction Insulin activates G6PDH
enzyme
• 2. High carbohydrate increases availability of
glucose and hence increases HMP shunt
and help lipogenesis
• Fasting decreases this pathway](https://image.slidesharecdn.com/class6hmppathway-150423001551-conversion-gate02/85/Class-6-hmp-pathway-19-320.jpg)
Uploaded byDhiraj Trivedi
Class 6 hmp pathway
The pentose phosphate pathway, also known as the hexose monophosphate shunt, generates NADPH and pentoses through oxidative and non-oxidative phases. It occurs mainly in the liver, erythrocytes, and adipose tissue. The oxidative phase produces NADPH and pentoses, while the non-oxidative phase interconverts the pentoses. The pathway provides reducing power for biosynthesis and maintains glutathione levels, protecting red blood cells from oxidative damage. Deficiencies in this pathway can cause hemolytic anemia and other conditions.
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Class 6 hmp pathway
- 1. Pentose phosphate pathway Putconfidence in GOD and get what he gives Put confidence in self and obtained what you want
- 2. Objectives - Gluconeogenesis •Definition • Other names • Occurrence and tissue distribution • Biomedical importance • Metabolic pathway • Clinical correlations • Regulation • Difference between EMP and HMP pathway
- 3. Definition : Hexose monophosphate pathway • Direct / alternate oxidative pathway for oxidative decarboxylation of glucose-6-phosphate at C-1, producing pentose sugars and NADPH + H+ • It is not involved in the generation of energy
- 4. Other names forpentose phosphate pathway • Hexose monophosphate pathway / shunt • Phosphogluconate pathway • Pentose phosphate cycle • Warburg -Dikens - Lipman pathway About 10% of glucose / day oxidised by this pathway
- 5. Location of thepathway • The enzymes of HMP shunt are located in the cytosol • Tissue actively participating are • Liver and Erythrocyte (30%) • Adipose tissue • Lactating mammary gland • Thyroid gland • Testes and • Adrenal cortex • Most of these tissue are involved in fatty acid and steroid synthesis and depends on NADPH
- 6. Overview of theshunt pathway • It has two phases • Oxidative phase • Glucose 6 phosphate is oxidised to generate two molecules of NADPH with liberation of one CO2 • Non oxidative phase • Pentose phosphate is converted to intermediates of glycolysis
- 7. Significance of HMPshunt • It has two main functions – provides • NADPH • Pentoses • These are utilized by other synthetic pathways
- 8. Importance of NADPH •Required for the biosynthesis of fatty acid, cholesterol, steroids. • Utilized in synthesis of certain amino acids involving glutamate dehydrogenase • Detoxification of drug and foreign compound by Cyt P450 need NADPH
- 9. Importance of NADPH •Required for the process of phagocytosis • Essential for maintaining integrity of RBC membrane and iron in ferrous state • Required for maintaining glutathione in reduced form
- 10. Importance of Pentoses •Converts pentose to hexose, tetrose, triose • Provides glycerol for TAG synthesis • Important for synthesis of Nucleic acid DNA & RNA • Synthesis of Nucleotides –ATP,NAD, FAD, CoA which acts as coenzymes and energy
- 11. 1 – OxidativePhase Glucose 6 Phosphate 6 Phosphogluconolactone 6 Phosphogluconate Glucose 6 Phosphate dehydrogenase 6 Phospho gluconolactonase NADP+ NADPH + H+ H2O Mg+2 • Reducing equivalent NADPH are generated • G6PDH is allosteric enzyme hence this is rate limiting step
- 12. 6 Phosphogluconate 3-Keto-6-Phosphogluconate D Ribulose5 Phosphate 6 Phosphogluconate Dehydrogenase NADP + NADP H + H+ CO2 Mg +2 • 3-Keto -6 – Phospho gluconate is spontaneously decrboxylated to Ribulose 5 phosphate • C-1 is eliminated as CO2, One more NADPH is produced 1 – Oxidative Phase
- 13. Phase 2 Nonoxidative phase Inter conversion of pentoses Ribulose 5 Phosphate Ribulose 5 Phosphate Ribulose 5 Phosphate Ribose 5 Phosphate Xylulose 5 Phosphate Xylulose 5 Phosphate Phospho pentose Isomerase Phospho pentose Epimerase Phospho pentose Epimerase 3 Ribulose 5 Phosphate
- 14. Phase 2 –Non oxidative phase • In this phase inter conversion of pentose to triose, tetrose, hexose and heptose takes place • Two specific enzymes required • 1. Transketolase – ( Thiamine pyrophosphate required as coenzyme) • 2. Transaldolase
- 15. Xylulose 5 Phosphate Xylulose 5 PhosphateRibulose5 Phosphate Phase 2 -- Non oxidative Steps conversion of pentoses to hexoses Glyceraldehyde 3 Phosphate Sedoheptulose 7 Phosphate Fructose 6 Phosphate Erythrose 4 Phosphate Transketolase Transaldolase TPP Glucose 6 Phosphate Transketolase Fructose 6 Phosphate Glyceraldehyde 3 Phosphate TPP Glucose 6
- 16.
- 18. In short HMPshunt • When started with six molecules of glucose, • Gives off 6 CO2 , 12 molecules of NADPH and 5 molecules of glucose regenerated • Complete oxidation of glucose 6 phosphate without involvement of mitochondria
- 19. Regulation of HMPshunt • Occurs in 3 ways: • 1. Ratio of [NADP]/[NADPH] , • G6PDH is rate limiting enzyme , it require NADP hence increase level of NADPH decreases reaction Insulin activates G6PDH enzyme • 2. High carbohydrate increases availability of glucose and hence increases HMP shunt and help lipogenesis • Fasting decreases this pathway
- 20. Regulation of HMPshunt • 3. Insulin and thyroid hormone favours reaction • Thus increase BGL increases insulin and increases HMP reactions • Insulin favours lipogenesis and uses NADPH thus increases NADP thereby increases HMP shunt
- 21. Clinical correlations • Deficiencyof Glucose 6 Phosphate dehydrogenase (G6PDH) leads to • Haemolytic Anaemia • Neonatal Jaundice • Liver cirrhosis • Kidney failure
- 22. G6PDH & Haemolysis •Due to deficiency of G6PDH, production of NADPH decreases, • NADPH is required for keeping Glutathione in its reduced form • Reduced Glutathione scavenges Free oxygen radical (ROS) • Deficiency leads to accumulation of methemoglobin and H2O2 • This damages RBC cell membrane and causes Haemolysis
- 23. H2O2 H2O 2 GSH G-S-S-G Reduced glutathione Oxidisedglutathione Glutathione peroxidase Glutathione reductase NADP+ NADPH + H+ Detoxication of hydrogen peroxide and Maintaining reduced glutathione
- 24. G6PDH & Haemolysis •Most of the patients with G6PD deficiency do not show any clinical symptoms but develop haemolytic anaemia & jaundice on exposure to oxidant drug • Drugs like Antimalarial, Analgesics, Antipyretics and sulpha aggravates the conditions (denature protein RBC- Heinz body) • Fava beans also have similar effect
- 25. Wernicke Korsakoff Syndrome •Genetic disorder associated with HMP shunt • Variant form of Transketolase. • Genetic alteration in Transketolase , reduces its affinity with TPP • Symptoms are • Mental disorders • Severe memory loss • Partial paralysis
- 26. Comparison of twopathways EMP pathway • Occurs in all tissue • Not a multi cyclic pathway • NAD + acts as H acceptor • ATP is generated • CO2 is not produced HMP pathway • Occurs only in specific tissue • Involves multi cyclic steps • NADP+ acts as H acceptor • ATP is not produced • CO2 is produced by oxidative decarboxylation