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It is an metabolic pathway of synthesis of glucose from non carbohydrate precursors like pyruvate, lactate, amino acid, glycerol etc. Main sites are liver and kidney. It uses enzymes from both cytosol and mitochondria.
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Part - I of amino acid metabolism.
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2. • Breakdown of glycogen to glucose is called as
glycogenolysis
• The degradation of stored glycogen in liver
and muscle constitutes glycogenolysis.
• The pathways for the synthesis and
degradation of glycogen are not reversible.
• An independent set of enzymes present in the
cytosol carry out glycogenolysis.
• Glycogen is degraded by breaking α(1- 4)- and
α (1,6)-glycosidic bonds
3.
4. 1. Action of glycogen phosphorylase
• The α-1,4-glycosidic bonds (from the non-
reducing ends) are cleaved sequentially by the
enzyme glycogen phosphorylase to yield
glucose1-phosphate.
This process is called phosphorolysis, Continues
until four glucose residues remain on either side
of branching point (α-1,6 glycosidic link).
The glycogen so formed is known as limit
dextrin which cannot be further degraded by
phosphorylase.
5. 2. Action of debranching enzyme
• The branches of glycogen are cleaved by two
enzyme activities present on a single
polypeptide called debranching enzyme,
hence it is a bifunctional enzyme.
• Glycosyl 4 : 4 transferase ( oligo α-1,4 --> l ,4
glucan transferase) activity removes a
fragment of three glucose residue from the
four glucose residues attached at a branch and
transfers them to another chain.
• Here, one α -1,4-bond is cleaved and the
same α -1,4 bond is made, but the places are
different.
6.
7. • Amylo α-1,6-glucosidase or glucosidase,
cleaves the remaining alpha-1,6 linkage, producing a
free glucose molecule and a linear chain of glycogen.
• The remaining glycogen is again available for the
action of phosphorylase and debranching enzyme to
repeat the reactions stated in 1 and 2.
8. 3. Formation of glucose 6-phosphate
and glucose
• Through the combined action of glycogen
phosphorylase and debranching enzyme,
glucose 1-phosphate and free glucose in a
ratio of 8 : 1 are produced.
• Glucose 1 phosphate is converted to
glucose-6-phosphate by the enzyme
phosphoglucomutase.
9. • The fate of glucose 6-phosphate depends on
the tissue.
• The liver, kidney and intestine contain the
enzyme glucose 6-phosphatase that cleaves
glucose-6–phosphate to glucose.
• This enzyme is absent in muscle and brain,
hence free glucose cannot be produced from
glucose 6-phosphate in these tissues.
• Therefore, liver is the major glycogen storage
organ to provide glucose into the circulation
to be utilised by various tissues.
10. • In muscle and brain, glucose-6-
phosphate produced by glycogenolysis
will be used for glycolysis.
• lt may be noted that though glucose-6-
phosphatase is absent in muscle some
amount of free glucose (8-10% of
glycogen) is produced in glycogenolysis
due to the action of debranching enzyme
(α-1,6-glucosidase activity)
11.
12. Regulation of glycogenolysis
• A good coordination and regulation of glycogen
synthesis and its degradation are essential to
maintain the blood glucose levels.
• Glycogenesis and glycogenolysis are, respectively,
controlled by the enzymes glycogen synthase
and glycogen phosphorylase.
• Regulation of these enzymes is accomplished by
three mechanisms
1 . Allosteric regulation
2. Hormonal regulation
3. lnfluence of calcium.
13. Allosteric regulation of glycogen
metabolism
• Glycogen breakdown is enhanced when glucose
concentration and energy levels are low.
• When there is high demand for ATP (low [ATP],
low [Glucose-6-P], and high [AMP]),
glycogen phosphorylase is stimulated
and glycogen synthase is inhibited, so flux
through this pathway favours Glycogenolysis.
14.
15. Effect of Ca2+ ions on glycogenolysis
• Insulin stimulated the activity of glycogen
synthase in muscle in the absence of
extracellular calcium.
• It is concluded that glycogen synthase is
under the control of calcium in the
glycogen storage tissues.
16. Hormonal Regulation
The overall effect of hormones on glycogen
metabolism is that an elevated glucagon or
epinephrine level increases glycogen
degradation,
whereas an elevated insulin results in increased
glycogen synthesis.