Fundamentals of
Biochemistry
Third Edition
Donald Voet • Judith G. Voet •
Charlotte W. Pratt
Chapter 16
Glycogen Metabolism and Gluconeogenesis
Copyright © 2008 by John Wiley & Sons, Inc.
Glycogen Breakdown
Enzymes for Glycogen Breakdown
• Glycogen phosphorylase
– Glycogen + Pi  Glycogen (n-1) + G1P
• Glycogen Debranching Enzyme
• Phosphoglucomutase
– G1P  G6P
• Glycogen Phophorylase
– Homodimer
– Regulation
• -- ATP, G6P, glucose
• + AMP
• Phosphorylation
– R & T states
– Crevase that holds 4-5
linear carbohydrates
– Cofactor of PLP, a B6
derivative
Debranching Enzyme
Phosphoglucomutase
Diseases
• G6P generated via glycogen has multiple fates
– Glycolysis
– Pentose phosphate
– Transport to other tissues
• In liver, G6Pase, removes phosphate for transport out of cell
• G6Pase is in the ER, but G6P is in cytosol
– G6P translocase
• Glucose exits cell via GLUT2
– Muscles lack G6Pase and therefore retain G6P
Glycogen Synthesis
• G’ for glycogen phosphorylase
is +3.1 kJ/mol
– Under physiological conditions it is
-5 to -8 kJ/mol
– This reaction then, cannot go both
directions spontaneously via the
same enzymes
UDP-Glucose Pyrophosphorylase
•
Since synthesis is thermodynamically
unfavorable, we must put in energy.
G1P + UTP ↔ UDPG + PPi = 0 kJ/mol
H2O + PPi  2 Pi
= -19.2 kJ/mol
Net
G1P + UTP  UDPG + 2 Pi
= -19.2 kJ/mol
Glycogen Synthase
The second step is
spontaneous under
physiological
conditions. It comes
at a cost of 1 ATP
(UTP)
Glycogen synthase
only adds to a chain
Need Glycogenin to
build initial starting
chain
Branching Enzyme
Must transfer 7
carbohydrates at
a time (only).
There must be at
least 4 left over.
Activated by
phosphorylation and Ca2+
Calcium is regulated
by calmodulin
PP1c
Hormonal Control
Increase Glycogen Breakdown
• Low Glucose
• ↑ Glucogon
• ↑ Epinephrine
– B-adrenergic receptor (muscle)
• ↑cAMP
– A-adrenergic receptor (liver)
• ↑ Glucogon
• ↑ cAMP
• ↑ Ca2+
Increase Glycogen Synthesis
• High Glucose
• Insulin
– GLUT4
• Muscle, fat
• ↓ cAMP
Gluconeogenesis
• Most of Gluconeogenesis
is Glycolysis in reverse.
• Only irreversible steps
must be different
• Oxaloacetate is the
required molecule to start
gluconeogenesis
Step 1 – Make oxaloacetate
normal
Oxaloacetate is only formed in the
mitochondria, remaining steps occur
in cytosol.
anaerobic
Same enzyme different domains
PFK
F1,6BP
O-linked
N-linked
N-linked