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G-6-P

Glucose 6 phosphatase. fructose 1,6 bis phosphatase. 1. pyruvate carboxylase. 2. phosphoenol pyruvate carboxy kinase. glucose. G-6-P. F-6-P. F-1,6-bisP. DHAP. G-3-P. 1,3,bis-PG. 3-P-G. 2-P-G. PEP. Pyruvate. from lactate. from pyruvate. OAA. pyruvate. pyruvate. PEP. Asp.

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G-6-P

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  1. Glucose 6 phosphatase fructose 1,6 bis phosphatase 1. pyruvate carboxylase 2. phosphoenol pyruvate carboxy kinase glucose G-6-P F-6-P F-1,6-bisP DHAP G-3-P 1,3,bis-PG 3-P-G 2-P-G PEP Pyruvate

  2. from lactate from pyruvate OAA pyruvate pyruvate PEP Asp malate mitochondrial matrix cytosol pyruvate malate Asp pyruvate lactate OAA OAA alanine PEP G3P dehydro G3P dehydro glucose

  3. malate dehydrog. NADH transaminase NAD PEPCK malate dehydro. NADH NADH LDH from lactate from pyruvate Pyruvate carboxylase Pyruvate carboxylase OAA pyruvate pyruvate PEP Asp malate mitochondrial matrix cytosol pyruvate malate Asp pyruvate transaminase transaminase lactate OAA OAA alanine PEPCK PEPCK PEP G3P dehydro G3P dehydro glucose

  4. Plants a1-4 + a1-6 glucose b1-4 glucose Cellulose Starch • amylose • amylopectin Glycogen Animals

  5. Structure of Glycogen A A A A A A A B B A B B B A B B B A B A B B B A A A A A A • each B-chain has two branch points • all chains have the same length of 14 residues • the material is distributed at 50% between A- and B-chains. • a molecule of glycogenin, a protein that acts as a primer, is located at the centre of the structure. See also amylopectin:fig 8-24 in Horton amylopectin

  6. 5 4 3 2 1 Structure of Glycogen A A A A A A A B B A B B B A B B B A B A B B B A A A A A A • each B-chain has two branch points • all chains have the same length of 14 residues • the material is distributed at 50% between A- and B-chains. • a molecule of glycogenin, a protein that acts as a primer, is located at the centre of the structure. • because synthesis and degradation takes place at non-reducing ends, branching provides more sites for these processes occur. See also amylopectin:fig 8-24 in Horton amylopectin

  7. After a meal as much as 10% by weight of the liver may be glycogen

  8. PKA [Gsa] R [GSb-PO4]T inactive PP1 active G6P [GSb-PO4]R active Regulation of glycogen synthase Allosteric: G6P Phosphorylation : inhibits

  9. Phosphorylase cleaves a1-4 bonds from the non-reducing termini of glycogen to yield Glucose -1-P

  10. Glycogen debranching enzyme

  11. Glycogen degradation: combined action of phosphorylase and debranching enzyme

  12. a 1 6 branching enzyme a 1 6

  13. Glycogen synthesis: glycogen synthase and branching enzyme a1-4 linkage autocatalysis UDP-glucosyltransferase autocatalysis several cycles glycogen synthase several cycles Amylo(1,4 1,6) transglycosylase (branching enzyme) a1-6 linkage glycogen synthase/ branching enzyme multiple cycles

  14. Regulation of phosphorylase Allosteric: AMP (muscle) G6P, ATP phosphorylation:

  15. 2ATP Phos kinase (liver, muscle) 2ADP 2Pi AMP (muscle) PP1 PO4 T G6P ATP PO4 Phos a inactive R glucose (liver) Phos b active PO4 R PO4 Phos a active Regulation of phosphorylase: part 2 T Phos b inactive

  16. Co-ordinated regulation of phosphorylase and glycogen synthase by PKA PP1 active PKA PP1-PO4 inactive GSb-PO4 GSa active inactive Phos kinasea-PO4 Phos kinaseb active inactive Ca2+ Phosb Phosa-PO4 active inactive See fig 13.7 Horton

  17. Ga Gb,g G-protein linked receptor Adenylate cyclase GDP GDP GTP GDP GDP GTP GTP Pi ATP cAMP + PPi GDP

  18. Adenyl cyclase ATP 3’5’ cyclic AMP + PPi Cyclic nucleotide phosphodiesterase AMP 3’5’ cyclic AMP 3’5’ cyclic AMP

  19. Regulation of PKA 4 cAMP C R R C R C R C inactive active

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