Glycogen MetabolismGlycogen Metabolism

Dr. Sooad Al-DaihanDr. Sooad Al-DaihanBiochemistry department Biochemistry department

Glycogen

Glycogen is a homopolysaccharide of D-glucose residues linked by:

α(14) glycosidic bonds, mainlyα(16) glycosidic bonds, at branch points.

Each branch is made of 6‐12 glucose units Glucose is stored as glycogen predominantly in liver and muscle

cells .

Function of Glycogen:Liver glycogen :•It maintains normal blood glucose concentration

especially during the early stage of fast (between meals) .

•After 12‐18 hours fasting, liver glycogen is depleted .

Muscle glycogen :•It acts as a source of energy within the muscle itself

especially during muscle contractions.•Muscle glycogen is depleted after prolonged

exercise.

Glycogenesis:Glycogenesis is the formation of glycogen in liver and

musclesIt occurs in the cytosol

gluconeogenesis

Continue.. Uridine diphosphate glucose (UDP‐glucose)

is the immediate precursor for glycogen synthesis

UDP‐glucose is formed from glucose‐1‐phosphate :

Cleavage of PPi is the only energy cost for glycogen synthesis (one ~P bond per

glucose residue)

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UDP-glucose

glucose-1-phosphate UTP

UDP-Glucose Pyrophosphorylase

Continue.. Glycogenin is an enzyme that

initiates glycogen synthesis by catalyzing the attachment of a glucose molecule to one of its

own tyrosine residues.UDP is released as a product

Glycogenin then catalyzes glucosylation at C4 of the attached glucose (UDP‐glucose again the donor), to yield an O‐linked disaccharide with α(14)

glycosidic linkage This is repeated until a short

linear glucose polymer (glycogen primer) with α(14) glycosidic linkages is built up on

Glycogenin .

Continue.. Glycogen Synthase then

catalyzes elongation of glycogen chains initiated by Glycogenin by transfering the glucose moiety of UDP-glucose to the hydroxyl at C4 of the terminal residue of a glycogen chain to form an (14) glycosidic linkage branches up to

11 glucose units .

A branching enzyme transfers a segment (minimum 6 Glc residues) from the end of a glycogen chain to the C6 hydroxyl of a glucose residue of glycogen to yield a branch with an α(16) linkage. The new branches are elongated by the glycogen synthase and the

process is repeated .

Glycogenolysis:Glycogenolysis is the breakdown of glycogen into

glucose (in liver) and lactic acid (in muscles).It occurs in the cytosol.Two major enzymes participate in all

glycogen degradation:Glycogen phosphorylaseGlycogen de-branching enzyme has 2

independent active sites, consisting of residues in different segments of a single

polypeptide chain :•Transferase •α (16) glucosidase

Continue.. Glycogen Phosphorylase (the key enzyme of glycogenolysis) catalyzes phosphorolytic cleavage (addition of Pi) of the α(14) glycosidic linkages of glycogen, releasing glucose‐1‐phosphate as

reaction product Always acts at nonreducing end,

stops at fourth glucose from α (16) branch point

The transferase transfers 3 glucose residues from a 4-residue limit branch to the end of another branch, diminishing the limit branch to a single glucose

residue. The α(16) glucosidase then

catalyzes hydrolysis of the α(16) linkage by adding H2O,

yielding free glucose

The major product of glycogen breakdown is glucose‐1‐phosphate, from Phosphorylase

activity .

Continue.. Glucose‐1‐P formed by phosphorolytic

cleavage of glycogen is converted into glucose‐6‐P by

Phosphoglucomutase Glucose 6‐phosphate derived from

glycogen can be :Used as a fuel for anaerobic or

aerobic metabolism as in, for instance, muscle ;

Converted into free glucose in the liver and subsequently released into the blood to maintain a

relatively level of blood glucose ;Processed by the pentose

phosphate pathway to generate NADPH or ribose in a variety of

tissues

Regulation of Glycogen Metabolism

Regulation by Covalent Modification

Continue.. Green=Acti

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Continue.. Green=Acti

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