BIOC 3560 Carb metabolism.docx

Regulated by redox state of the cytosol glycogen

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Regulated by redox state of the cytosol Glycogen metabolism Glycogen: polymer of glucose (storage); quick source of energy Liver: glycolysis + control of blood glucose concentrations Muscle: glycolysis Glycogen synthesis – making the precursor:
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o Glucose 6-P glucose 1-P (phosphoglucomutase) o Glucose 1-P + UTP UDP-glucose + PPi (UDP-glucose pyrophosphorylase) *UDP-glucose then acts as an activated sugar donor Glycogen synthase reaction UDP-glucose + nonreducing end of a glycogen chain with n residues (n>4) elongated glycogen with n+1 residues and has a new nonreducing end + UDP This uses enzyme glycogen synthase Glycogenolysis (glycogen breakdown) – glycogen phosphorylase reaction Glycogen chain + Pi glucose 1-P + glycogen shortened by one residue This uses the enzyme glycogen phosphorylase Regulation of glycogen metabolism Glycogen synthase is inhibited by phosphorylation o PKA and GSK3 phosphorylate it at different sites, and they also have different degrees of synthase inactivation o GSK3 is a stronger inhibitor compared to PKA Glycogen phosphosphorylase is activated by phosphorylation Glycogen phosphrylase b kinase o Phosphorylates glycogen phosphorylase o Activates glycogen phosphorylase Glycogen phosphorylase a phosphatase o Dephosphorylates glycogen phosphorylase o Inhibits glycogen phosphorylase The activity of glycogen phosphorylase b kinase is stimulated by PKA-mediated phosphorylation Glycogen phosphorylase is a glucose sensor Glucose binding of phosphorylase a has an allosteric effect This favours dephosphorylation (and inactivation) by phosphorylase a phosphatase Insulin activates phosphorylase a phosphatase Glycogen synthase and glycogen phosphorylase are reciprocally regulated by phosphorylation PKA-mediated regulation of carbohydrate metabolism in the liver PKA regulation ensures that low blood sugar leads to increased glycogen breakdown, and decreased glycogen synthesis and glycolysis Hormone-regulated enzyme activity coordinates tissue-specific metabolism
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Epinephrine and glucagon signal the need for glucose, however, glucagon only works in the liver as muscle does not react to it In the liver, glycogen and pyruvate will convert to G6P then blood glucose In the muscle, glycogen will turn to G6P then pyruvate These signals will cause an increase in glycogenolysis and gluconeogenesis in the live, and a decrease in glycolysis In the muscle, glycogenolysis will increase, so will glycolysis Tissue-specific metabolism Why are muscle and liver metabolism different? o Myocytes lack glucagon receptros o Muscle pyruvate kinase is not phosphorylated by PKA o Muscle lacks gluconeogenic enzymes o Muscle lacks a key enzyme for glucose export bc muscle uses stored glycogen and glucose for itself
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