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Cellular Biochemistry and Metabolism (CLS 333 )

Cellular Biochemistry and Metabolism (CLS 333 ). Dr. Samah Kotb Nasr Eldeen. Topics were covered in theoretical part. pentose phosphate pathway Gluconeogenesis Glycogen synthesis Glycogenolysis. Topics were covered in practical part. lab safety. Pentose phosphate pathway.

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Cellular Biochemistry and Metabolism (CLS 333 )

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  1. Cellular Biochemistry and Metabolism(CLS 333 ) Dr. Samah Kotb Nasr Eldeen

  2. Topics were covered in theoreticalpart • pentose phosphate pathway • Gluconeogenesis • Glycogen synthesis • Glycogenolysis

  3. Topics were covered in practical part • lab safety

  4. Pentose phosphate pathway

  5. The PPP can be divided into two phases • The oxidative phase generates NADPH which is required for many biosynthetic pathways and for detoxification of reactive oxygen species.

  6. The nonoxidative phase interconverts C3 , C4 , C5,C6 and C7 monosaccharides to produce ribose-5P for nucleotide synthesis, and also to regenerate glucose-6-P to maintain NADPH production by the oxidative phase.

  7. The reversible non-oxidative phase • In non-oxidative phase, ribulose 5-P is converted back to G-6-P by a series of reactions involving especially two enzymes 1. Transketolase 2. Transaldolase

  8. Importance of Pentose Phosphate Pathway Ribulose-5-P may be converted to ribose-5-phosphate, a substrate for synthesis of nucleotides, nucleic acids and coenzymes The pathway also produces some NADPH

  9. Glyceraldehyde-3-P and fructose-6-P may be converted to glucose-6-P,via enzymes of gluconeogenesis, for reentry to Pentose Phosphate Pathway, maximizing formation of NADPH, which is need for reductive biosynthesis.

  10. Regulation of pentose phosphate pathway • The entry of glucose 6-phosphate into the pentose phosphate pathway is controlled by the cellular concentration of NADPH • NADPH is a strong inhibitor of glucose 6-phosphate dehydrogenase (Rate Limiting Reaction) • As NADPH is used in various pathways, inhibition is relieved, and the enzyme is accelerated to produce more NADPH

  11. Regulation of the G6PD activity controls flux through the glycolytic pathway and pentose phosphate pathways

  12. Gluconeogenesis

  13. Gluconeogenesis Pathway: Gluconeogenesis enzyme names in red. Glycolysis enzyme names in blue. Dr.SamahKotb

  14. Dr.Samah Kotb

  15. The Cori cycle costs 6 ~Pin liver for every 2 ~P made available in muscle. The net cost is 4 ~P. Although costly in ~P bonds, the Cori Cycle allows the organism to accommodate to large fluctuations in energy needs of skeletal muscle between rest and exercise. Dr.SamahKotb

  16. Energy dissipation by the Cori Cycle, which expends 6 ~P in liver for every 2 ~P produced via Glycolysis for utilization within the tumor, is thought to contribute to the weight loss that typically occurs in late-stage cancer even when food intake remains normal. Dr.Samah Kotb

  17. Glycogen Catabolism

  18. Glucose 6-phosphate has 3 fates.

  19. Glycogen phosphorylase catalyzes the breakdown of glycogen. Glycogen + Pi  Glucose 1- phosphate + glycogen (n residues) (n-1 residues)

  20. Phosphorylase is specific for the α-1,4 linkage. Two additional enzymes are required

  21. Hormonal Regulation of Glycogen Catabolism

  22. Glucagon Stimulate Glycogen breakdown • Liver is responsive to glucagon • Glucagon signal, a cascade of molecular events leading to glycogen breakdown. • It utilizes a G-protein-dependent signal-transduction pathway.

  23. Glucagon A few hormone molecules cause the release of large amounts of glucose, a cascade.

  24. Glycogen Synthesis

  25. UDP-glucose pyrophosphorylase Glucose 1-phosphate + UTP  UDP-glucose + PPi. ppi + H2O → 2Pi. Glucose 1-phosphate + UTP + H2O → UDP-glucose + 2Pi. Although the reaction is reversible the hydrolysis of the pyrophosphate pushes it to the right.

  26. Glycogen synthase catalyzes α-1,4 linkages A primer of a least 4 units are required via glycogenin. Glucose is added to the non-reducing end. UDP

  27. Hormonal Regulation

  28. Glycogen synthesis and breakdown are reciprocally regulated Red=inactive forms, green = active forms. Inactive Active Protein phosphatase 1 (PP1) regulates glycogen metabolism.

  29. Protein Phosphatase 1 • PP1 dephosphorylates phosphorylase kinase and phosphorylase a, thus inactivating glycogenolysis. • PP1 also dephosphorylates glycogen synthase b, thus activating glycogen synthesis.

  30. PP1 dephosphorylates phosphorylase kinase and phosphorylase a thus inactivating glycogenolysis.

  31. PP1 dephosphorylates glycogen synthase b thus activating glycogen synthesis

  32. Blood glucose levels rise after ingestion of carbohydrates, leading to glycogen synthesis. Inactivation of phosphorylase and an activation of glycogen synthase. Liver

  33. Insulin is a Peptide Hormone Glycogen synthesis and degradation • Insulin is secreted from the pancreas(to liver) in response to an increase inblood glucose • Insulin stimulates glycogen synthesisand inhibits glycogen breakdown • Note that the portal vein is the only vein in the body that feeds an organ • Note the other effects of insulin

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