Glycogen Metablism

Glycogen Metabolism
Preamble
 Only in animals, microbes-why?????
 Effect of osmolarity
 The elementary particle of glycogen consists of up to 55,000 glucose residues with
about 2,000 non reducing ends. 20 to 40 of theses form alpha rosette
 Store lost within 24 hours of fasting even within 12 hours but varies in case of liver and muscle depending upon
situation.
 Differential function of muscle and liver glycogen

 Glycogen is a quicker energy providing source both for aerobic and anaerobic process
 Liver store house-glucose balance-provide fuel to other tissues-nerves specially as they cant use fats as fuel
 Glycogen level is too low compared to Tgs-why?

 Glycogen reserve is highly important as Mammals cant use fat for gluconeogenesis and anaerobically
 Glycogen granules are complex aggregates of glycogen and the enzymes that synthesize it and degrade it, as
well as the machinery for regulating these enzymes.
The general mechanisms for storing and mobilizing glycogen are the same in muscle and liver but the
enzymes differ in subtle yet important ways that reflect the different roles of glycogen in the two tissues
Glycogen Breakdown
Phosphorylosis vs Hydrolysis
Different from amylase

reaction(intestinal
breakdown)
Pyridoxal phosphate is an essential

cofactor in the glycogen
phosphorylase reaction; its
phosphate group acts as a general
acid catalyst, promoting attack by p1
on the glycosidic bond
In skeletal muscle and liver, the glucose units of the outer branches of glycogen enter the glycolytic pathway
through the action of three enzymes: glycogenphosphorylase, glycogen debranching enzyme and
phosphoglucomutase
Glycogen Breakdown
1. Alpha 1 4 breaks under

the attack of phosphate Four residues from
the branching point
2. Transfer of glucose
residues
3. Breaking of alpha 1 4
Transferase
4. G1P to G6P
Glucosidase-
Hydrolysis not
phosphorylosis
Tissue Based Actions
Initially, phosphorylated at a Ser residue,

the enzyme donates a phosphoryl group to
C-6 of the substrate, then accepts a
phosphoryl group fromC-1
 Muscle
 Kidney, Liver-G-6-phosphatase, ER transport and ………….
Because muscle and adipose tissue lack glucose-6- phosphatase, they cannot convert the glucose-6-phosphate formed
by glycogen breakdown to glucose and these tissues therefore donot contribute glucose to the blood.
Glycogen breakdown to Glucose
Glycolysis and gluconeogenesis are separated

Glycogen Metabolic Disorders
Glycogen Synthesis
Many of the reactions in which hexoses are transformed or polymerized involve sugar nucleotides, compounds in which the
anomeric carbon of a sugar is activated by attachment to a nucleotide through a phosphate-ester Iinkage. Sugar
nucleotides are the substrates for polymerization of monosaccharides into disaccharides, glycogen, starch, cellulose and more
complex extracellular polysaccharides. They are also key intermediates in the production of the aminohexoses and deoxyhexoses
found in some of these polysaccharides, and in the synthesis of vitamin C(l-ascorbic acid).
 Metabolically irreversible
 Non-covalent Interactions of nucleotide atoms with enzyme
release additional binding energy to ease the catalysis.
 Tagging the products and separating them from glycolysis
 Ease nucleophilic attack and activate C-1 of sugar carbon
Reversible but actually

not?
Glycogen Synthesis
Intermediate donor in
glycogen synthesis
 G-6-p is starting
material
 Phosphoglucomutase
 Cori cycle
Adding at non reducing end-why?

Branching of glycogen
 Solubility & reducing ends

 Access
How the reaction is Initiated?
Co-ordinated Regulation of Synthesis and
Breakdown
 The mobilization of stored glycogen is brought about by glycogen phosphorylase, which degrades glycogen to
glucose 1-phosphate.
 Glycogen phosphorylase provides an especially instructive case of enzyme regulation. It was one of the first
known examples of an allosterically regulated enzyme and the first enzyme shown to be controlled by
reversible phosphorylation.
 It was also one of the first allosteric enzymes for which the detailed three-dimensional structures of the active
and inactive forms were revealed by x-ray crystallographic studies.
Key Enzymes Regulation
cAMP
PKA
Pbk
Glucose sensor
Glucose-6-p sensor
FOR GSK
Phosphorylation of the hydroxyl side chains of several Ser residues of both subunits converts glycogen synthase a to
glycogen synthase b, which is inactive unless its allosteric activator, glucose 6-phosphate,is present. Glycogen synthase is
remarkable for its ability to be phosphorylated on various residues by at least 11 different protein kinases. The most
important regulatory kinase is glycogen synthase kinase 3 (GSK3), which adds phosphoryl groups to three Ser residues
near the carboxyl terminus of glycogen synthase, strongly inactivating it. The action of GSK3 is hierarchical; it cannot
phosphorylate glycogen synthase until another protein kinase, casein kinase II (CKII), has first phosphorylated
the glycogen synthase on any near by residue, an event called priming.
In liver, conversion of glycogen synthase b to the active form is promoted by PP1, which is bound to the
glycogen particle. PPl removes the phosphoryl groups from the three Ser residues phosphorylated by GSK3.
Glucose6-phosphate binds to an allosteric site on glycogen synthase b, making the enzyme a better substrate
for dephosphorylation by PPI and causing its activation. By analogy with glycogen phosphorylase, which acts as
a glucose sensor, glycogen synthase can be regarded as a glucose-6-phosphate sensor.
In muscle, a different phosphatase may have the role played by PPl in liver,
activating glycogen synthase by dephosphorylating it.
Regulatory Systems
Regulatory System
The END

Glycogen Metablism

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Glycogen Metabolism

 Differential function of muscle and liver glycogen

 Glycogen level is too low compared to Tgs-why?

Different from amylase

Pyridoxal phosphate is an essential

1. Alpha 1 4 breaks under

Initially, phosphorylated at a Ser residue,

 Kidney, Liver-G-6-phosphatase, ER transport and ………….

Glycolysis and gluconeogenesis are separated

Reversible but actually

Adding at non reducing end-why?

 Solubility & reducing ends

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