Glycogen Metabolism
C483 Spring 2013
1. Why does glycolysis produce more energy (more ATP) from glucose units released by glycogen degradation than from free glucose?A) Limit dextrin contains additional molecules.B) The debranching enzyme releases free glucose.C) The glucose is already phosphorylated after glycogen phosphorylase action.D) The glucose from glycogen degradation bypasses glycolysis.E) All of the above.
2. What is the driving force for the reaction catalyzed by UDP-glucose pyrophosphorylase that converts glucose 1-phosphate to UDP-glucose?A) The subsequent hydrolysis of pyrophosphate.B) The formation of an energy-rich product.C) Its large negative free energy change. D) The change in concentration of UTP.
3. Glycogen phosphorylase is ________ (more, less) active when not phosphorylated, and it is ________ (activated, inhibited) by glucose 6-phosphate. A) more; activated B) less; activated C) more; inhibited D) less; inhibited
Glucose Metabolism Overview
• Keep the main pathway purposes distinct
• But learn details of chemistry and regulation based on similarities
OHO
HO
OH (P)
OH
OH
DHAP
Pyruvate
Gluconeogenesis
Lactate
Amino Acids
Glycerol(Triacylglycerides)
Glycogen
Glycogen Degradation
Glycogen
Glycogen Synthesis
Ribose,NADPH
ATP
DHAP
Pyruvate
Pentose Phosphate Pathway
Energy Production
Starch
Diet
Glycogen
• Storage molecule• Primer necessary• Very large!• Multiple ends allow
for quick synthesis and degradation
Chemistry of Synthesis
• Step 1
• Near equilibrium• The link to glucose-6-phophate, our central
molecule
O
H
HO
H
HO
H
OH
OHHH
OP
O
H
HO
H
HO
H
O
OHHH
OH
PO3-2Glucose-6-phosphate glucose-1-phophate
Chemistry of Synthesis• Step 2
• Count high energy bonds• Pyrophosphatase• UDP-glucose: activated for incorporation
OHO
HO
O
OH
OH
NH
O
ONO
OHOH
OPOO
OPO
OOP
O
OO
P
O
O O
OHPO
OOP
O
OO 2 Pi
OHO
HO
O
OH
OH
NH
O
ONO
OHOH
OPOO
OPO
O
Chemistry of Synthesis• Step 3
• Growing end is non-reducing• UDP released
Energetics of Synthesis
• Total cost: one ATP equivalent
OHO
HO
O
OH
OH
P
O
O O
OHO
HO
O
OH
OH
P-P-Uridine
OHO
OH
OH
OH
O
O
OH
HO
O
HO
Glucose-6-PUDP
UTP
2 Pi
Chemistry of Degradation
• Inorganic phosphate as a nucleophile
Overall Energetics
OHO
HO
O
OH
OH
P
O
O O
OHO
HO
O
OH
OH
P-P-Uridine
OHO
OH
OH
OH
O
O
OH
HO
O
HO
Glucose-6-PUDP
UTP
2 Pi
Pi
Key Enzymes
OHO
HO
O
OH
OH
P
O
O O
OHO
HO
O
OH
OH
P-P-Uridine
OHO
OH
OH
OH
O
O
OH
HO
O
HO
Glucose-6-PUDP
UTP
2 Pi
Pi
Glycogen Synthase
Glycogen Phosphorylase
Regulation of Glycogen Phosphorylase b
• Prototype of Allosteric regulation
• Happens in muscle exertion
Hormone Regulation
• Glucagon• Signal Transduction• Covalent Modification• Glycogen phosphorylase b becomes glycogen
phosphorylase a
Regulation of Glycogen Phosphorylase a
• Relaxed state now favored
• No allosteric effects except glucose deactivation in the liver
Glucagon and Insulin
• Act Reciprocally on Glycogen synthase and Glycogen phosphorylase
Maintenance of Blood Sugar
Answers
1. C2. A3. D