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Gluconeogenesis ط       Definition and Importance , ط      Reactions and irreversibility

Gluconeogenesis ط       Definition and Importance , ط      Reactions and irreversibility ط      Substrates : Glycerol, Lactate, Glucogenic amino acids, Odd chain fatty acids                                    D4 299-308. Introduction

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Gluconeogenesis ط       Definition and Importance , ط      Reactions and irreversibility

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  1. Gluconeogenesis ط      Definition and Importance , ط     Reactions and irreversibility ط     Substrates : Glycerol, Lactate, Glucogenic amino acids, Odd chain fatty acids                                    D4 299-308

  2. Introduction § Gluconeogenesis is formation of glu from non-carbohydrate (CHO) source § Main tissues: liver, kidneys § Substrates: lact, pyr, glucogenic AA (T7.2), glycerol, propionate § Other sugars: Fru, Gal, Man § Opposite of glycolysis:               *  GK/HK َ G6P-tase (located on surface of endo retic fig7.37) *  PFK1 َ F1,6BP-tase *  PK َ PC + PEPCK § Occur during starvation, diabetes, Cushing's syndrome, intense exercise & high cortisone dose § Inhibited:       -  during shortage of oxygen & use of uncouplers: pathway goes towards glycolysis - by ethanol (produce NADH), opposite use:     * LDH (pyr => lact)                         * MDH (OA => M-ate) § Regulation by hormonal (INS/GLG ratio), allosteric & substrate

  3. Importance 1. When glu is not sufficient in diet: § Glu is main source of energy in brain (aerobically) § Glu is main source of energy in muscle & RBCs (anaerobically) § Glu is main source of glycerol-3-phosphate in adipose tissue (no glycerol kinase) § Glu is source of intermediates for TCA cycle § Glu is precursor for lactose (milk sugar) 2. To clear tissue metabolites: Lact from muscle & RBCs Glycerol from adipose tissue (AT)

  4. Reactions • 1.  fig7.33,  • (2) Lactate  (2) Pyr  (2) OA  PEP  Asp  OA  PEP • fig7.32a, Cori Cycle: • Glu in RBCs (glycolysis) => +2 ATP & 2 Lact => .........Table • Lact in Liver (gluconeogenesis) => –6 ATP & 1 Glu=> • Glu in RBCs (glycolysis) + 2 ATP + 2 Lact • 2. fig7.38,  • (2) alanine (2) Pyr (2) OA M-ate OA PEP Asp M-ate OA PEP • fig7.32b, Alanine Cycle : • Glu in RBCs (glycolysis) => 2 Pyr => +8 ATP & 2 ala => .........Table • ala in Liver (gluconeogenesis)=> 2 Pyr => –6 ATP & 1 Glu=> • Glu in RBCs (glycolysis) => 2 Pyr =>  +8 ATP + 2 Ala

  5. 3. Glucogenic AA   1-  Pyr  OA  M-ate  OA  PEP (not leu & lys)     2-  α-KG  SCoA  S-ate  F-ate  M-ate  OA  PEP 3- SCoA  S-ate  F-ate  M-ate  OA  PEP 4-  F-ate  M-ate  OA  PEP 5-  OA  M-ate  OA  PEP 6-  3PG  2PG  PEP  Pyr  OA  M-ate  OA  PEP 4.  fig7.40, (2) Propionate  (2) MCoA  (2) SCoA => (2) OA  (2) PEP 5.  fig7.41, (2)Glycerol  (2) G3P  (2) DHAP  DHAP + GAP  F1,6BP 6.  fig7.42, Fructose  F1P  DHAP Glyceraldehyde  Glycerol  G3P  DHAP  GAP 7.  fig7.43, Glucose  Sorbitol / Sucrose  Fructose 8.  fig7.44, Galactose  Gal 1 P  G1P  G6P  Glu 9.  Mannose  M6P  F6P  G6P  Glu

  6. Regulation of Gluconeogenesis ط     Hormonal regulation ط      reciprocality with glycolysis ط     Factors affecting gluconeogenesis ط      Cori and Alanine cycles                                    D4 308-312

  7. Regulation 1. Regulation of glycolytic enzymes a)  Glu  GK/HK  G6P GK (–) by F6P (GKRP), GLG (+) by F1P (GKRP), INS * HK (–) by G6P b) F6P  PFK1  F1,6P2 (–) by ATP, citrate (FA oxid/CAC), GLG (+) by AMP, F2,6BP c) PEP  PK  Pyr (–) by ATP, ala, ACoA, GLG (+) by F1,6BP

  8. Regulation 2.  Regulation of gluconeogenic enzymes a) Pyruvate  PC  OA (+) ACoA (FA oxid) b) OA  PEPCK  PEP (–) by INS * (+) GLG *, ala          fig7.46 c) F1,6BP  F1,6BP-tase  F6P (–) by AMP, F2,6BP (+) by F1,6BP d) G6P  G6P-tase  Glucose (+) GLG Note:*INS & GLG regulate gene expression (synthesis) NOT by phosph/dephosphorylation

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