Glycogen Metabolism

Reducing end

Glycogen MetabolismGlycogen Breakdown (Glycogenolysis) and Glycogen SynthesisWhy breakdown glycogen and not lipid to produce glc?1. Mobilized faster2. Can be metabolized anaerobically

Glycogen breakdownGlc units are removed one at a time from the nonreducing ends by phosphorolysis

Glycogen MetabolismGlycogen BreakdownRemove all the 14 branches and an additional enzyme is rec’d to remove 16

Glycogen MetabolismGlycogen Breakdown - Glycogen phosphorylaseFirst known example of an allosterically regulated enzymeFirst enzyme shown to be controlled by reversible phosphorylation

In muscle:

Resting muscle

During vigorous muscular activity, epinephrine triggers phos

Triggers glycogen breakdown

Glycogen MetabolismGlycogen Breakdown - Glycogen phosphorylaseIn liver:

Low blood sugar - glucagon activates phosphorylase b kinase, initiates release of glc into blood

phosphorylase kinase

Glycogen MetabolismGlycogen Breakdown Fate of glucose 1-phosphateMuscle / liver phosphoglucomutase

G1P G6P Glycolysis

If you just need glucose:LiverGluconeogenesis or glucose 6-phosphatase

Glycogen G1P G6P + H2O Glc + Pi

In brain & muscle:No gluconeogenesis and no glucose 6-phosphatase soget 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 MetabolismGlycogen SynthesisWant to polymerize glc, need an activated form of glc - UDP-glucoseOccurs in almost all tissues, especially in liver and muscle

UDP-glucose pyrophosphorylase

Glycogen synthase

UDP

Glycogenchain

Glycogen chain + one more glucose residue

Glycogen MetabolismGlycogen Synthesis

Glycogen MetabolismGlycogen Synthesis

Glycogen Metabolism

Glycogen SynthesisGlycogen 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 MetabolismGlycogen SynthesisGlycogen synthase cannot make the (16) bonds found at branches, these are formed by branching enzymes

Glycogen MetabolismGlycogen SynthesisGlycogen synthase cannot make the (16) bonds found at branches, these are formed by branching enzymes

Glycogen MetabolismControlHormones reciprocally regulate synthesis and degradation by controlling the phosphorylation/dephosphorylation of the key enzymes

Glycogen MetabolismControlHormones reciprocally regulate synthesis and degradation by controlling the phosphorylation/dephosphorylation of the key enzymes

Glucagon, epinephrine: stimulate phosphorylaseinhibit synthase

Insulin: inhibit phosphorylasestmulate synthase

(+) Glucagon, epinephrine

(+) Insulin

Glycogen MetabolismControlHormones reciprocally regulate synthesis and degradation by controlling the phosphorylation/dephosphorylation of the key enzymesGlucagon, epinephrine: stimulate phosphorylase & inhibit synthaseInsulin: inhibit phosphorylase & stimulate synthase

Glycogen Metabolism

Glycogen Metabolism

Glycogen Metabolism

Glycogen Metabolism