Glycogen Metabolism Reducing end

Glycogen Metabolism Glycogen Breakdown (Glycogenolysis) and Glycogen Synthesis Why breakdown glycogen and not lipid to produce glc? 1. Mobilized faster 2. Can be metabolized anaerobically Glycogen breakdown Glc units are removed one at a time from the nonreducing ends by phosphorolysis

Glycogen Metabolism Glycogen Breakdown Remove all the 14 branches and an additional enzyme is rec’d to remove 16

Glycogen Metabolism Glycogen Breakdown - Glycogen phosphorylase First known example of an allosterically regulated enzyme First enzyme shown to be controlled by reversible phosphorylation In muscle: Resting muscle Glucagon, Epinephrine, Ca2+, AMP During vigorous muscular activity, epinephrine triggers phos Triggers glycogen breakdown

Glycogen Metabolism Glycogen Breakdown - Glycogen phosphorylase In liver: phosphorylase kinase Low blood sugar - glucagon activates phosphorylase b kinase, initiates release of glc into blood

Glycogen Metabolism Glycogen Breakdown Fate of glucose 1-phosphate Muscle / liver phosphoglucomutase G1P  G6P  Glycolysis If you just need glucose: Liver Gluconeogenesis or glucose 6-phosphatase Glycogen  G1P  G6P + H2O  Glc + Pi In brain & muscle: No gluconeogenesis and no glucose 6-phosphatase so get glc from gluconeogenesis in liver or from injested glc, both of which get delivered through bloodstream In liver, glycogen is a reservoir of glc, converted into blood glc that moves to other tissues In muscle, glycogen breakdown produces glc that is metabolized via glycolysis to provide ATP for muscle contraction

Glycogen Metabolism Glycogen Synthesis Want to polymerize glc, need an activated form of glc - UDP-glucose Occurs in almost all tissues, especially in liver and muscle UDP-glucose pyrophosphorylase Glycogen chain Glycogen synthase UDP Glycogen chain + one more glucose residue

Glycogen Metabolism Glycogen Synthesis

Glycogen Metabolism Glycogen Synthesis

Glycogen Metabolism Glycogen Synthesis Glycogen synthase cannot initiate a chain - it needs a primer Protein enzyme glycogenin makes the primer Once 8 glucose molecules have been added, Glycogenin-[glc]8 is a substrate for glycogen synthase

Glycogen Metabolism Glycogen Synthesis Glycogen synthase cannot make the (16) bonds found at branches, these are formed by branching enzymes

Glycogen Metabolism Control Hormones reciprocally regulate synthesis and degradation by controlling the phosphorylation/dephosphorylation of the key enzymes

Glycogen Metabolism Control Hormones reciprocally regulate synthesis and degradation by controlling the phosphorylation/dephosphorylation of the key enzymes Glucagon, epinephrine: stimulate phosphorylase inhibit synthase Insulin: inhibit phosphorylase stmulate synthase (+) Insulin (+) Glucagon, epinephrine