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The concentration of glucose residues stored as glycogen in liver is
~0.4M, Whereas, glycogen concentration is only 10 nM.
IV: Large amount of glucose can be stored without affecting the
osmolarity of the cells.
So that multiple glycogen phosphorylases can act at several
non-reducing ends of glycogen chains to generate large amount
of Glucose-1-P for glycolysis, or to release glucose in blood very
quickly.
3. Glycogen Debranching enzyme:
Glycogen phosphorylase proceeds along glycogen chain until it
approaches close to (about 4-5 residue away) the a (1—6) branch
point.
Glycogen debranching enzyme takes over from here. This protein has
two activities;
1. Acts as an a(1-4) transglycosylase or glycosyltransferase: It
transfers an a(1-4)-linked trisaccharide unit from the limit branch to
the nonreducing end of another branch.
2. This enzyme also has a separate site for the a(1—6) glucosidase
activity, by which it hydrolyses the remaining glucose of the branch
liked by a(1—6) link to the main chain releasing free glucose not
the G1P.
Approximately 10% of the total glucose residues generated from
glycogen breakdown are as free glucose and 90% as G1P.
Glycogen Synthesis: This part will be covered in Metabolism II.
However, for the purpose of understanding the regulation of
glycogen metabolism it is briefly mentioned below.
Glycogen synthesis is achieved by three enzymes
I. UDP-glucose phosphorylase
II. Glycogen synthase
III. Branching enzyme
Regulation of Glycogen metabolism: Glycogen is stored in liver
and muscle as emergency energy source. Its breakdown during
need of energy and it’s synthesis to replenish the store is tightly
regulated. Glycogen metabolism is regulated both by different
metabolites present in the cells as well as by hormones through
signal transduction cascades.
Activities of the two enzymes of glycogen metabolism are critical for
the control of this pathway
1. Glycogen phosphorylase
2. Glycogen synthase
The enzymatic activities of Glycogen phosphorylase and glycogen
synthase are controlled by two ways;
I. By direct allosteric control
II. By covalent modification
Allosteric controle:
G6P and ATP are allosteric
inhibitors of Glycogen
phosphorylase whereasAMP
is an allosteric acivator.
G6P is an allosteric activator
of activator of glycogen
synthase.
Control by phosphorylation:
Phosphorylase ‘a’
(phosphorylated form) is
more active than
phosphorylase ‘b’
(dephosphorylated form.
Phosphorylase ‘a’ is
insensitive to inhibition by
ATP
Insulin-stimulated protein kinase
Glycogen Storage Diseases: These are inherited disorders which are
caused by defects in the genes encoding enzymes involved in synthesis
and break down of glycogen.
The defects in liver enzymes generally cause hepatomegaly (enlarged
liver) and hypoglycemia whereas those in muscle enzymes generally
cause muscle cramps.
Type I: Glucose 6-Phosphatase deficiency (von Gierke’s Disease): This
enzyme catalyses step which leads to the delivery of glucose in blood
stream from liver. In the absence of this enzyme, liver is unable to
release glucose in blood, leading to hypoglycemia. Ther is build up of
G6P in the liver which activates glycogen synthase leading to buold og
huge glycogen store and hepatomgaly. Treatments include, inhibition of
glucose by liver by drugs and , contineoud intragastric feeding
overnight and liver transplantation.
Type VI: Liver phosphorylase deficiency (Her’s Disease): Patients
unable to use liver glycogen. Symptoms and treatments are similar to
type I disease.
Type IV: Branching enzyme deficiency (Anderson’s Disease):
Presence of unbrached long chains of glycogen, which become
insoluble particles, causing sever liver malfunction. The abnormal
size particle may trigger immune response that causes liver damage
and death of the patients within 4 yr of age.
Type 0: Liver glycogen synthase deficiency: This is the only disease
of glycogen metabolism where there is deficiency of glycogen.
Hyperglycmia after the meals and hypoglycemia in other times.
Type V: Muscle phosphorylase deficiency (McArdle’s Disease):
symptoms appear in adulthood with severe muscle cramps after
strenuous exercise. Blood glucose remain unaffected.