GLYCOGEN METABOLISM
Glycogen is the storage form of carbohydrates in the humanbody. The major sites of
storage are liver and muscle. Themajor function of liver glycogen is to provide
glucose during starvation.
When blood glucose level lowers, liver glycogen is broken down and helps to
maintain blood glucose level.
The function of muscle glycogen is to act as reserve fuel for muscle contraction.
After taking food, blood sugar tends to rise, which causes glycogen deposition in
liver. About 5 hours. after taking food, the blood sugar tends to fall. But, glycogen is
lyzed to glucose so that the energy needs are met.
After about 18 hours fasting, most of the liver glycogen is depleted, when depot fats
are hydrolyzed and energy requirement is met by fatty acid oxidation.
Degradation of Glycogen (Glycogenolysis)
Glycogen Phosphorylase
The enzyme glycogen phosphorylase removes glucose units one at a time from the non
reducing end of the glycogen molecule. The product is glucose-1-phosphate
Phosphorylase sequentially attacks alpha-1,4 glycosidic linkages, till it reaches a branch
point .It cannot attack the 1,6 linkage at branch point.
Debranching Needs Two Enzymes
With the help of glucan transferase and debranching enzyme (alpha-1,6-glucosidase), the
branching point is also hydrolysed. This glucose. residue is released as free glucose. With
the removal of branch, phosphorylase enzyme can now proceed with its action.
Phosphoglucomutase
Phosphorylase reaction produces glucose-1 phosphate while debrancher enzyme releases
glucose. The glucose-1-phosphate is converted to glucose-6-phosphate by
phosphoglucomutase.
Glucose-6-phosphatase in Liver
Next, hepatic glucose-6-phosphatase hydrolyzes glucose-6-phosphate to glucose. The
product of hepatic glycogenolysis is free glucose, which is released to the bloodstream.
Muscle Lacks Glucose-6-phosphatase
But muscle will not release glucose to the blood stream, because muscle tissue does
not contain the glucose-6-phosphatase.
, ii. The energy yield from one glucose residue derived from glycogen is 3 ATP
molecules, because no ATP is required for initial phosphorylation of glucose (step 1 of
glycolysis). If glycolysis starts from free glucose only 2 ATPs are produced.
Glycogen Synthesis (Glycogenesis)
The glycogen synthesis occurs by a pathway distinctly different from the reversal of
glycogen breakdown.
Activation of Glucose
UDP glucose is formed from glucose-1-phosphate and UTP (uridine triphosphate) by the
catalytic activity of UDP-glucose pyrophosphorylase.
Glucose-1 phosphate +UTP UDP-glucosepyrophosphorylase UDP-glucose+ PPi
Glycogen Synthase
In the next step, activated glucose units are sequentially added by the enzyme glycogen
synthase. The glucose unit from UDP-glucose is transferred to a glycogen primer molecule.
Glycogen primer(n) + UDP-glucose Glycogen(n+1) + UDP
The glucose unit is added to the nonreducing (outer) end of the glycogen to form an alpha-
1,4 glycosidic linkage and UDP is liberated.
The primer is essential as the acceptor of the glycosyl unit. The glycogen primer is formed
by glycosylation of glycogenin (a dimeric protein). This molecule acts as the glycogen primer
to which glucose units are added by glycogen synthase.
Brancher Enzyme
A branching enzyme is needed to create the alpha 1,6 linkages .To this newly created
branch, further glucose units can be added in alpha 1,4 linkage by glycogen synthase.
Branching makes the molecule more globular.
Regulation of Glycogen Metabolism
The synthesis and degradation pathways are reciprocally regulated to prevent futile
cycles.
The phosphorylated form of glycogen phosphorylase is active whereas glycogen
synthase becomes relatively inactive on phosphorylation.
The covalent modification of these enzymes is brought by hormones that act through
a second messenger, cyclic AMP (CAMP).
Generation of Cyclic AMP (CAMP)
Both liver and muscle phosphorylases are activated by a cyclic AMP mediated
activation cascade triggered by the hormonal signal.
Glycogen is the storage form of carbohydrates in the humanbody. The major sites of
storage are liver and muscle. Themajor function of liver glycogen is to provide
glucose during starvation.
When blood glucose level lowers, liver glycogen is broken down and helps to
maintain blood glucose level.
The function of muscle glycogen is to act as reserve fuel for muscle contraction.
After taking food, blood sugar tends to rise, which causes glycogen deposition in
liver. About 5 hours. after taking food, the blood sugar tends to fall. But, glycogen is
lyzed to glucose so that the energy needs are met.
After about 18 hours fasting, most of the liver glycogen is depleted, when depot fats
are hydrolyzed and energy requirement is met by fatty acid oxidation.
Degradation of Glycogen (Glycogenolysis)
Glycogen Phosphorylase
The enzyme glycogen phosphorylase removes glucose units one at a time from the non
reducing end of the glycogen molecule. The product is glucose-1-phosphate
Phosphorylase sequentially attacks alpha-1,4 glycosidic linkages, till it reaches a branch
point .It cannot attack the 1,6 linkage at branch point.
Debranching Needs Two Enzymes
With the help of glucan transferase and debranching enzyme (alpha-1,6-glucosidase), the
branching point is also hydrolysed. This glucose. residue is released as free glucose. With
the removal of branch, phosphorylase enzyme can now proceed with its action.
Phosphoglucomutase
Phosphorylase reaction produces glucose-1 phosphate while debrancher enzyme releases
glucose. The glucose-1-phosphate is converted to glucose-6-phosphate by
phosphoglucomutase.
Glucose-6-phosphatase in Liver
Next, hepatic glucose-6-phosphatase hydrolyzes glucose-6-phosphate to glucose. The
product of hepatic glycogenolysis is free glucose, which is released to the bloodstream.
Muscle Lacks Glucose-6-phosphatase
But muscle will not release glucose to the blood stream, because muscle tissue does
not contain the glucose-6-phosphatase.
, ii. The energy yield from one glucose residue derived from glycogen is 3 ATP
molecules, because no ATP is required for initial phosphorylation of glucose (step 1 of
glycolysis). If glycolysis starts from free glucose only 2 ATPs are produced.
Glycogen Synthesis (Glycogenesis)
The glycogen synthesis occurs by a pathway distinctly different from the reversal of
glycogen breakdown.
Activation of Glucose
UDP glucose is formed from glucose-1-phosphate and UTP (uridine triphosphate) by the
catalytic activity of UDP-glucose pyrophosphorylase.
Glucose-1 phosphate +UTP UDP-glucosepyrophosphorylase UDP-glucose+ PPi
Glycogen Synthase
In the next step, activated glucose units are sequentially added by the enzyme glycogen
synthase. The glucose unit from UDP-glucose is transferred to a glycogen primer molecule.
Glycogen primer(n) + UDP-glucose Glycogen(n+1) + UDP
The glucose unit is added to the nonreducing (outer) end of the glycogen to form an alpha-
1,4 glycosidic linkage and UDP is liberated.
The primer is essential as the acceptor of the glycosyl unit. The glycogen primer is formed
by glycosylation of glycogenin (a dimeric protein). This molecule acts as the glycogen primer
to which glucose units are added by glycogen synthase.
Brancher Enzyme
A branching enzyme is needed to create the alpha 1,6 linkages .To this newly created
branch, further glucose units can be added in alpha 1,4 linkage by glycogen synthase.
Branching makes the molecule more globular.
Regulation of Glycogen Metabolism
The synthesis and degradation pathways are reciprocally regulated to prevent futile
cycles.
The phosphorylated form of glycogen phosphorylase is active whereas glycogen
synthase becomes relatively inactive on phosphorylation.
The covalent modification of these enzymes is brought by hormones that act through
a second messenger, cyclic AMP (CAMP).
Generation of Cyclic AMP (CAMP)
Both liver and muscle phosphorylases are activated by a cyclic AMP mediated
activation cascade triggered by the hormonal signal.
