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: 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
If you just need glucose:
Liver
Gluconeogenesis or
Glycogen → G1P →
→ Glycolysis
glucose 6-phosphatase
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 (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
(+)
Insulin
(+)
Glucagon,
epinephrine
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