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 α1→4 branches and an additional enzyme is rec’d to remove α1→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

During vigorous muscular activity, epinephrine triggers phos

Triggers glycogen breakdown

Glycogen Metabolism Glycogen Breakdown - Glycogen phosphorylase In liver:

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

phosphorylase kinase

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 synthase

UDP

Glycogen chain

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 (α1→6) bonds found at branches, these are formed by branching enzymes

Glycogen Metabolism Glycogen Synthesis Glycogen synthase cannot make the (α1→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

(+) Glucagon,

epinephrine

(+) Insulin

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 & stimulate synthase

Glycogen Metabolism

Glycogen Metabolism

Glycogen Metabolism

Glycogen Metabolism