HMP pathway and its significance. Biochemistry. pptx

Hmp

1. HMP pathway and its significance Alina George | Mam Yad-e-Baiza Nawal | Govt. Post Graduate College

2. HMP SHUNT PATHWAY DEFINITION: It is a metabolic pathway parallel to glycolysis. It generates NADPH and pentoses essential in body for various reasons. WHY HMP PATHWAY IS CALLED SHUNT? It is called HMP SHUNT PATHWAY because the pathway allows for carbon atoms from glucose-6-phosphate to take a brief detour (shunt) before they proceed down the glycolytic pathway. 2/17/2020 2

3. HMP Pathway Phospho gluconate pathway Pentose phosphate pathway Hexose monophosphate pathway All the intermediates of this pathway are in the mono phosphate form contrary to glycolysis where bisphosphate forms of intermediates are also there. 2/17/2020 3

4. What is the purpose of HMP pathway ? An alternative route for the metabolism of glucose What is the outcome: NADPH Pentoses Not directly meant for energy production 2/17/2020 4

5. Where does this pathway take place? ORGANS?TISSUES Rapidly dividing cells and in tissues where there is a great requirement of NADPH such as: Liver Adipose tissue Adrenal cortex Gonads Lens RBC’s The pathway is less active in the skeletal muscle.

6. HMP Pathway All the reactions of this pathway take place in the cytoplasm. 2/17/2020 6

7. HMP pathway an overview

8. 2/17/2020 8

9. Oxidative phase leads to formation of Ribose 5-P by oxidative decarboxylation Non oxidative phase rearrangement process results in the formation of glycolytic intermediates 2/17/2020 9

10. Oxidative phase

11. Reactions of oxidative phase of HMP pathway-2 molecules of NADPH and one of are produced in the oxidative phase   2/17/2020 11

12. STEP-1: Glucose-6-phosphate is oxidized by enzyme glucose-6-phosphate dehydrogenase to form 6-phosphoglucono- -lactone. This enzyme is an NADP dependent enzyme, where accepts an electron to form NADPH +   2/17/2020 12

13. STEP-2: The product 6-phosphoglucono- -lactone gets hydrolyzed to 6-phosphogluconate by a specific enzyme lactonase .   2/17/2020 13

14. STEP-3: The product 6-phosphogluconate gets decarboxylated to give D-ribulose 5-phosphate. 2/17/2020 14

15. Non-Oxidative phase

16. Reactions of HMP pathway – Non-Oxidative phase Ribulose 5-phosphate 3-epimerase(Phosphopentose epimerase) alters the configuration about carbon 3, forming the epimer Xylose 5-phosphate, also a ketopentose Ribose 5-phosphate keto Isomerase (phosphopentose isomerase) converts Ribulose 5-phosphate to the corresponding aldopentose, ribose 5-phosphate 2/17/2020 16

17. Non-Oxidative phase The pathway catalyzes the interconversion of: 3,4,5,6 and 7 carbon sugars in a series of non oxidative reactions That can result in the synthesis of: 5-carbon sugars for nucleotide biosynthesis or Degradation of excess 5-carbon sugars into intermediates of the glycolytic pathway. 2/17/2020 17

18. Rearrangement of sugars in the Non-Oxidative Phase C5+C5 C3+C7 C3+C7 C6+C4 C5+C4 C3+C6 2/17/2020 18

19. STEP-1-Non-Oxidative phase 2/17/2020 19

20. STEP-1 Non-oxidative phase Transketolase effects the conversion of a ketose sugar into an aldose with 2-carbons less and an aldose sugar into a ketose with 2 carbons more. The reaction requires and thiamine pyrophosphate(vitamin B1) as coenzyme   2/17/2020 20

21. STEP-2-Non-Oxidative phase 2/17/2020 21

22. STEP-3-Non-Oxidative phase 2/17/2020 22

23. Significance of HMP pathway

24. Major outcomes NADPH Pentoses Glycolytic intermediates   2/17/2020 24

25. Significance of NADPH It is used for reductive biosynthesis For maintenance of membrane integrity of red blood cell and lens, detoxification and macrophageal functions 2/17/2020 25

26. Significance of pentoses 2/17/2020 26

27. NUCLEOTIDES: 2/17/2020 27

28. ATP: 2/17/2020 28

29. COENZYMES: 2/17/2020 29 NADP FAD

30. Utilization of Pentoses Non-Oxidative phase of HMP Pathway 2/17/2020 30

31. Significance of Glycolytic intermediates Glyceraldehyde-3-Phosphate and Fructose-6-Phosphate formed may enter glycolysis for ATP synthesis or may be used as intermediates of pathway of gluconeogenesis( metabolic process used to make sugars from non-carbohydrate precursors) The Pentose Phosphate Pathway thus serves as an entry into Glycolysis for both 5-carbon and 6-carbon sugars. 2/17/2020 31

32. Significance of   produced from this pathway can be utilized for fixation reactions, Such as: Pyruvate to Oxaloacetate Acetyl co A to Malonyl co A Gamma carboxylation of glutamic acid residues etc. Propionyl co A to Methyl malonyl co A   2/17/2020 32

33. PYRUVATE TO OXALOACETATE: 33 2/17/2020

34. ACETL CO-A TO MALONYL CO-A: 34 2/17/2020

35. GAMMA CARBOXYLATION OF GLUTAMIC ACID: 35 2/17/2020

36. PROPIONY CO-A TO METHYL MALONYL CO-A: 36 2/17/2020

37. Clinical significance Glucose-6-phosphate dehydrogenase (GSPD) deficiency An X-linked disorder Asymptomatic or hemolytic anemia Anemia may be associated with hemoglobinemia(excess of hemoglobin in blood plasma) and hemoglobinuria( excretion of free hemoglobin in urine) 2/17/2020 37

38. Pathophysiology of hemolytic Anemia Reduced glutathione (GSH) , a tripeptide with a free sulfhydryl group is required to combat oxidative stress and maintain the normal reduced state in the cell Oxidized glutathione (GSSG) is reduced by NADPH generated by glucose 6-phosphate dehydrogenase in the pentose phosphate pathway Cells with reduced levels of glucose 6-phosphate dehydrogenase are especially sensitive to oxidative stress 2/17/2020 38

39. Treatment of hemolytic Anemia in G6PD deficiency Identification and discontinuation of the precipitating agent is critical in cases of glucose-6-phosphate dehydrogenase(G6PD) deficiency Affected individuals are treated with oxygen and bed rest, which may afford symptomatic relief Prevention of drug-induced hemolysis is possible in most cases by choosing alternative drugs 2/17/2020 39

40. THANKYOU FOR LISTENING… REFERENCES: www.slideshare.net 7 th February,2020 www.pharmaexchange.info 16 th February, 2020 www.ncbi.nlm.nih.gov/books/NBK551687/ 16 th February ,2020 www.watcut.uwaterloo.ca/webnotes/Metabolism/HMS.html 16 th February ,2020 2/17/2020 40