Please enable JavaScript.
Coggle requires JavaScript to display documents.
Class 9. Glycogen Metabolism (Structure of glycogen (linkages (alpha 1->…
Class 9. Glycogen Metabolism
Physiological functions of glycogen
Metabolic stages and Whole-Body metabolism
five metabolic stages
Stage I (absorptive)
Exogenous glucose used for blood glucose supply
Brain uses glucose as major fuel
Stage II-III
(post-absorptive)
Glycogen
and gluconeogenesis
used for blood glucose supply
Stage II: Glycogenolysis
used more than gluconeogenesis (4-16 hrs after meal)
Stage III: Gluconeogenesis used more than glycogenolysis (16 hrs to 2 days after meal)
Brain uses glucose as major fuel
Stage IV-V (starvation and prolonged starvation)
Brain uses glucose AND ketone bodies as major fuel
Gluconeogenesis used for blood glucose
Functional significance (Slide 13)
Structure of glycogen
monomer: glucose
linkages
alpha 1->4 (linear)
alpha 1->6 (branches)
difference from amylopectin?
comparable to
amylopectin
Location of glycogen
Tissue-level
liver
Use glycogen for?
muscle
Use glycogen for?
Cell-level: cytosolic space
granules
catabolic enzymes (outside)
anabolic enzymes (core)
Regulation of glycogen metabolism
Hormonal control
:
insulin/glucagon
Response to blood glucose level
epinephrine/norepinephrine
Response to stress situation
Covalent Modification of enzymes
Glycogen phosphorylase
Activated in response to low glucose levels in blood
Glucagon
Activated in response to stress
Adrenaline (= epinephrine)
Cascade regulation
Metabolic control
Allosteric regulation of enzymes
Example: Glycogen phosphorylase
Response to changing levels of metabolites
ATP, AMP, Glucose, Glucose 6-P
Example: More active form (phosphorylase a) can be transiently inhibited if glucose level goes up significantly (Slide 51)
Reactions, enzymes and intermediates (Slide 15)
Metabolites involved (intermediates, product)
Glucose 6-P
UDP-glucose
Glucose 1-P
Glucose
Glycogen synthesis: Reactions
Glucose to Glucose 6-P
Enzyme: Glucokinase
Glucose 6-P to Glucose 1-P
Glucose 1-P to ?
Products
?
UDP Glucose to Glycogen By Glycogen Synthase
Inorganic Pyrophosphate (PPi)
further cleaved by inorganic pyrophosphatase
2 Pi
Glucose 1 P to UDP glucose by UDP Glucose Pyrophosphorylase
Enzyme: Phosphoglucomutase
? reacts with glycogen
Product: Glycogen
Enzyme
Glycogenin
For initial synthesis of 10-20 glucosyl units
??
For elongation
Branching
Branching enzyme
amylo-(1,4-->1,6)transglycosylase
7 glucosyl residues (linear) are moved to a new branching point
New branching point is about 4 residues from existing branch
Glycogen degradation: Reactions
Cleavage of alpha 1-4 linkage
Enzyme: Glycogen phosphorylase
Product: Glucose 1-P
conversion of Glucose 1-P to Glucose 6-P
Enzyme: Phosphoglucomutase
Glucose 6 P
Glucose 6-P to Glucose
Enzyme: Glucose 6 phosphatase
location: ER
Product: glucose
Cleavage of alpha 1->6 linkage
First, move 3-4 residue branch to a nearby branch
Then, cleave one glucose with alpha 1->6 linkage
Enzyme: glycogen debranching enzyme
This enzyme has both activities of moving 3-4 residues and alpha 1-6 cleavage