Code and Title of the Paper: F10NB Nutritional Biochemistry Code and Title of the Module: F10NB04 Glycogen Metabolism and Hexose Monophosphate Shunt Name of the Content Writer: Dr. S. Sumathi Quadrant - I 4.1. GLYCOGEN METABOLISM The major site of daily glucose consumption (75%) is the brain via aerobic pathways. Most of the remainder of is used by erythrocytes, heart muscle, and skeletal muscle. The body gets glucose either directly from the diet or from amino acids and lactate via gluconeogenesis. Glucose got from these two primary sources either remains soluble in the body fluids or is stored in a polymeric form, glycogen. Glycogen is considered the main storage form of glucose and is found mostly in liver and muscle. The kidney and intestines adds minor storage sites. With up to 10% of its weight as glycogen, the liver has the maximum specific content of any body tissue. Muscle has a much lower quantity of glycogen per unit mass of tissue, but since the total mass of muscle is so much greater than that of liver, total glycogen stored in muscle is about twice that of liver. Glycogen storage in the liver are considered the main buffer of blood glucose levels. OBJECTIVES - To give an overview of glycogen metabolism - To understand the factors that control the glycogen metabolism by intracellular signalling - To understand the function of the pentose phosphate pathway in production of NADPH and ribose precursors for nucleic acid synthesis. Summary Glycogen is the animal storage form of branched poly(glucose). The storage polysaccharide of animals is glycogen. All cells contain glycogen, but it is most prevalent in the liver and the muscles. Glycogen comprises of glucose molecules linked together with α(1 →4)linkages with α(1 →6) branch points occurring every 8 to 12 residues. The purpose of the high branched structure is to have many nonreducing ends so that glucose can be rapidly mobilized in times of metabolic needs.Glycogen homeostasis involves the concerted regulation of the rate of glycogen synthesis (glycogenesis) and the rate of glycogen breakdown (glycogenolysis). These two processes are reciprocally regulated such that hormones that stimulate glycogenolysis (e.g. glucagon, cortisol, epinephrine, norepinephrine) at the same time inhibit glycogenesis. Conversely, insulin, which directs the body to store excess carbon for
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Code and Title of the Paper: F10NB Nutritional Biochemistry
Code and Title of the Module: F10NB04 Glycogen Metabolism and Hexose Monophosphate
Shunt
Name of the Content Writer: Dr. S. Sumathi
Quadrant - I
4.1. GLYCOGEN METABOLISM
The major site of daily glucose consumption (75%) is the brain via
aerobic pathways. Most of the remainder of is used by erythrocytes, heart muscle, and skeletal muscle. The body gets glucose either directly
from the diet or from amino acids and lactate via gluconeogenesis. Glucose got from these two primary sources either remains soluble in
the body fluids or is stored in a polymeric form, glycogen. Glycogen is considered the main storage form of glucose and is found mostly in liver
and muscle. The kidney and intestines adds minor storage sites. With up to 10% of its weight as glycogen, the liver has the maximum specific
content of any body tissue. Muscle has a much lower quantity of glycogen per unit mass of tissue, but since the total mass of muscle is
so much greater than that of liver, total glycogen stored in muscle is about twice that of liver. Glycogen storage in the liver are considered
the main buffer of blood glucose levels.
OBJECTIVES
- To give an overview of glycogen metabolism
- To understand the factors that control the glycogen metabolism by intracellular signalling
- To understand the function of the pentose phosphate pathway in
production of NADPH and ribose precursors for nucleic acid synthesis.
Summary
Glycogen is the animal storage form of branched poly(glucose). The
storage polysaccharide of animals is glycogen. All cells contain glycogen, but it is most prevalent in the liver and the muscles. Glycogen comprises of glucose molecules linked together with α(1 →4)linkages with α(1 →6)
branch points occurring every 8 to 12 residues. The purpose of the high branched structure is to have many nonreducing ends so that glucose
can be rapidly mobilized in times of metabolic needs.Glycogen
homeostasis involves the concerted regulation of the rate of glycogen synthesis (glycogenesis) and the rate of glycogen breakdown
(glycogenolysis). These two processes are reciprocally regulated such that hormones that stimulate glycogenolysis (e.g. glucagon, cortisol,
epinephrine, norepinephrine) at the same time inhibit glycogenesis. Conversely, insulin, which directs the body to store excess carbon for
Code and Title of the Paper: F10NB Nutritional Biochemistry
Code and Title of the Module: F10NB04 Glycogen Metabolism and Hexose Monophosphate
Shunt
Name of the Content Writer: Dr. S. Sumathi
future use, stimulates glycogenesis while concurrently inhibiting glycogenolysis.
Introduction
Glycogen metabolism is vital for several reasons.
• Glycogen stores in the liver are used to maintain a constant blood
glucose concentration. Glycogen storage is also maintained by muscles as
a reservoir of glucose for strenuous muscular activity.
• The synthesis and degradation of glycogen take place by different
metabolic pathways allowing for reciprocal regulation.
• In addition, the enzymes of glycogen metabolism are under hormonal
regulation.
The biochemical pioneers of glycogen metabolism were the Cori’s, Carl
and Gerty, a husband and wife team. They demonstrated that the
glycogen is broken down by phosphorolysis. The complete breakdown
process of glycogen breakdown is:
(glucose)n → glucose-1-phosphate + (glucose)n-1.
Processes of glycogen synthesis is:
(glucose)n-1 + UDP-glucose → (glucose)n
The glycogen breakdown and synthesis is controlled by two key enzyme
(glycogen phosphorylase and glycogen synthase) activities which are
activated/inactivated by allosteric regulation and phosphorylation /
dephosphorylation.
The storage form of glucose in most eukaryotic cells (except plants) is
glycogen, a large highly branched polysaccharide containing glucose units
joined by α-1→4 and α-1→6 glycosidic bonds. Both the liver and muscle
store glycogen and hence have the necessary anabolic and catabolic
enzymes. The degradation and synthesis of glycogen occurs in the cytosol
and the substrate for these reactions is the free ends of the branched
polymer. The large number of branch points in glycogen results in the
Code and Title of the Paper: F10NB Nutritional Biochemistry
Code and Title of the Module: F10NB04 Glycogen Metabolism and Hexose Monophosphate
Shunt
Name of the Content Writer: Dr. S. Sumathi
generation of multiple nonreducing ends that provide a highly efficient
mechanism to quickly release and store glucose.
4.1.1.GLYCOGEN SYNTHESIS - Luis Leloir discovered the glycogen
biosynthetic pathway.
Glycogen + UDP-glucose → Glycogenn+1 + UDP
If we compare the synthetic pathway to the degradative pathway it is
clear that the glycogen biosynthesis is not merely the reversal of the
degradative pathway. The two pathways are distinct providing a
mechanism for reciprocal control.
A. UDP-glucose formation by UDP-glucose pyrophosphorylase - In the
glycogen synthesis pathway, at first, the uridine diphosphate(UDP) is
attached to glucose. The reaction is catalyzed by UDP-glucose
pyrophosphorylase.
B. Glycogen synthesis by glycogen synthase
1.The glycosidic bond between glucose and UDP in UDP-glucose is
hydrolyzed.
2. The glucose unit of UDP-glucose is transferred to the C4-OH group on
one of glycogen’s non-reducing ends to form an α (1→4) glycosidic bond.
Code and Title of the Paper: F10NB Nutritional Biochemistry
Code and Title of the Module: F10NB04 Glycogen Metabolism and Hexose Monophosphate
Shunt
Name of the Content Writer: Dr. S. Sumathi
C. Glycogen Branching -
Glycogen synthetase can synthesize α(1→4) linkages. Another enzyme is
required to form the α(1→6) linkages that make the branches. The
branching enzymes takes a block of seven or so residues of a nonreducing
end and transfers these seven residues to an interior site and creates an
α(1→6) linkage. The chain that contributes the seven residues must be at
least 11 residues long, and the new branch point must be at least four
residues away from pre-existing branch points. About 7 units of the non-
reducing end of α-amylose chain are removed at α(1→4) linkage, and
reattached to the C6 of other α-amylose chain by α(1→6) linkage. This
transfer is carried out by amylo-(1,4→1→6)-transglycosylase (branching
enzyme).
Code and Title of the Paper: F10NB Nutritional Biochemistry
Code and Title of the Module: F10NB04 Glycogen Metabolism and Hexose Monophosphate
Shunt
Name of the Content Writer: Dr. S. Sumathi
4.1.2.GLYCOGENOLYSIS
Three enzymes are required for glycogen breakdown
1. Glycogen phosphorylase
Code and Title of the Paper: F10NB Nutritional Biochemistry
Code and Title of the Module: F10NB04 Glycogen Metabolism and Hexose Monophosphate
Shunt
Name of the Content Writer: Dr. S. Sumathi
(Glycogen)n + Pi ↔
(glycogen)n-1 + G1P (n residues).
Glycogen phosphorylase catalyzes this reaction. Glycogen phosphorylase
catalyzes the successive phosphorolysis of glucose residues from a
nonreducing end. The phosphorylated glucose cannot diffuse out of the
cell. Glycogen phosphorylase requires a pyridoxl-5’-phosphate cofactor.
The pyridoxl-5’-phosphate cofactor is covalently bound to a lysine residue