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Glucose 6 phosphatase glucose G-6-P F-6-P fructose 1,6 bis phosphatase F-1,6-bisP DHAP G-3-P 1,3,bis-PG 3-P-G 2-P-G 1. pyruvate carboxylase 2. phosphoenol pyruvate carboxy kinase PEP Pyruvate from lactate from pyruvate OAA pyruvate PEP pyruvate Asp malate mitochondrial matrix cytosol pyruvate Asp malate pyruvate lactate OAA OAA alanine PEP G3P dehydro G3P dehydro glucose from lactate pyruvate from pyruvate Pyruvate carboxylase Pyruvate carboxylase malate NADH dehydrog. PEPCK transaminase NAD PEP Asp malate OAA pyruvate mitochondrial matrix cytosol pyruvate LDH NADH lactate malate pyruvate malate transaminase NADHtransaminase dehydro. Asp OAA OAA PEPCK PEPCK PEP G3P dehydro G3P dehydro glucose alanine Cellulose b1-4 glucose Plants Animals Starch • amylose • amylopectin Glycogen a1-4 + a1-6 glucose Structure of Glycogen A A A A A A A B B A B B B B A A B B B A B B A • • • • B 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 Structure of Glycogen A A A 5 A A B B 3 B 2 1 B B B B B A A 4 A A A B A B B A B 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 After a meal as much as 10% by weight of the liver may be glycogen Regulation of glycogen synthase Allosteric: G6P Phosphorylation : [Gsa] R active PKA PP1 inhibits [GSb-PO4]T inactive G6P [GSb-PO4]R active Phosphorylase cleaves a1-4 bonds from the non-reducing termini of glycogen to yield Glucose -1-P Glycogen debranching enzyme Glycogen degradation: combined action of phosphorylase and debranching enzyme a1 6 branching enzyme a1 6 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 Regulation of phosphorylase Allosteric: AMP (muscle) G6P, ATP phosphorylation: Regulation of phosphorylase: part 2 2ATP T AMP (muscle) Phos kinase (liver, muscle) Phos b inactive 2ADP 2Pi PP1 PO4 T G6P ATP PO4 Phos a inactive R Phos b active glucose (liver) PO4 R PO4 Phos a active Co-ordinated regulation of phosphorylase and glycogen synthase by PKA GSa GSb-PO4 active inactive PP1 active PKA PP1-PO4 inactive Phos kinaseb inactive See fig 13.7 Horton Phos kinasea-PO4 active Ca2+ Phosb Phosa-PO4 inactive active Gb,g G-protein linked receptor Ga Adenylate cyclase GDP GDP GTP GDP GDP GTP GTP Pi ATP GDP cAMP + PPi 3’5’ cyclic AMP Adenyl cyclase ATP 3’5’ cyclic AMP + PPi Cyclic nucleotide phosphodiesterase AMP 3’5’ cyclic AMP Regulation of PKA R C R C inactive 4 cAMP R R C C active