The document discusses glycogen degradation (glycogenolysis). It describes the four enzymes involved - phosphorylase, debranching enzyme, phosphoglucomutase, and glucose-6-phosphatase. Phosphorylase breaks down glycogen into glucose-1-phosphate. The debranching enzyme and phosphorylase work together to further degrade glycogen. Phosphoglucomutase converts glucose-1-phosphate to glucose-6-phosphate which can then be used for energy or converted to glucose by glucose-6-phosphatase in the liver. The pathway provides glucose between meals and for anaerobic activity.
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The glucuronic acid pathway is a quantitatively minor route of glucose metabolism. Like the pentose phosphate pathway, it provides biosynthetic precursors and inter-converts some less common sugars to ones that can be metabolized.
Gluconeogenesis: Defined as biosynthesis of glucose from non-carbohydrate precursors
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-Regulation of Gluconeogenesis, hormonal and transcriptional regulation
coordination between different metabolic pathways inside the body is called integration of metabolism. this presentation discuss about how metabolism can be regulated and integrated in liver, muscle and adipose tissue.
Glycogenolysis pathway and its regulation a detailed study.AnjaliKR3
glycogenolysis detailed study. Glycogen breakdown pathway explained each step in detail. regulation of glycogenolysis pathway. allosteric regulation, hormonal regulation and calcium ion regulation.
The glucuronic acid pathway is a quantitatively minor route of glucose metabolism. Like the pentose phosphate pathway, it provides biosynthetic precursors and inter-converts some less common sugars to ones that can be metabolized.
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-Regulation of Gluconeogenesis, hormonal and transcriptional regulation
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Glycogen is the storage form of Glucose which maintain the blood glucose level under various condition. Glycogen Metabolism is the important pathway of carbohydrate metabolism which gives the information about the glycogen synthesis (Glycogenesis), Glycogen breakdown (Glucogenolysis). Glycogen metabolism also gives the information how this pathway is regulated. Their are various diseases which are associated with this metabolism, commonly known as Glycogen storage diseases.
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2. Learning objectives
To understand:
The Purpose
Role of Enzymes and coenzymes, and
The steps involved in the pathway of Glycogenolysis
1/6/2017Namrata Chhabra, M.D., Biochemistry 2
3. Introduction
Glycogen is a storage form of glucose.
It is a very large, branched polymer of glucose residues that
can be broken down to yield glucose molecules when energy
is needed.
Most of the glucose residues in glycogen are linked by α-1,4-
glycosidic bonds.
Branches at about every tenth residue are created by α-1,6-
glycosidic bonds.
1/6/2017Namrata Chhabra, M.D., Biochemistry 3
5. Purpose of Glycogenolysis
The controlled breakdown of glycogen and release of
glucose increase the amount of glucose that is
available between meals. Hence, glycogen serves as a
buffer to maintain blood-glucose levels.
Glycogen's role in maintaining blood glucose levels is
especially important because glucose is virtually
the only fuel used by the brain, except during
prolonged starvation.
1/6/2017Namrata Chhabra, M.D., Biochemistry 5
6. Purpose of Glycogenolysis
The glucose from glycogen is readily mobilized and
is therefore a good source of energy for sudden,
strenuous activity.
Unlike fatty acids, the released glucose can provide
energy in the absence of oxygen and can thus
supply energy for anaerobic activity.
1/6/2017Namrata Chhabra, M.D., Biochemistry 6
7. Enzymes involved in Glycogenolysis
The efficient breakdown of glycogen requires four
enzyme activities:
one to degrade glycogen,
two to remodel glycogen so that it remains a
substrate for degradation, and
one to convert the product of glycogen breakdown
into a form suitable for further metabolism.
1/6/2017Namrata Chhabra, M.D., Biochemistry 7
9. Major coenzyme of Glycogenolysis
Pyridoxal phosphate (PLP), a derivative of vitamin
B6, is the major coenzyme involved in the glycogen
degradation.
serves as prosthetic group for Glycogen
Phosphorylase.
It is held at the active site of Phosphorylase enzyme
by a Schiff base linkage, formed by reaction of the
aldehyde group of PLP with the ε-amino group of a
lysine residue.
1/6/2017Namrata Chhabra, M.D., Biochemistry 9
10. Glycogen degradation is not just the
reverse of glycogenesis
Glycogenesis
Glucose-> Glucose-6-P
Glucose-6-P –> Glucose-1-P
Polymerization
Branching
Polymerization
Glycogenolysis
Depolymerization- Removal of
glucose as glucose-1-P
Debranching
Depolymerization
Conversion of Glucose-1-P to
Glucose-6-P
Conversion of Glucose-6-P to
free Glucose
1/6/2017Namrata Chhabra, M.D., Biochemistry 10
11. Specific steps of Glycogenolysis
Step-1- Depolymerization (Release of Glucose-1-P from
Glycogen)
Enzyme- Phosphorylase
Coenzyme– Pyridoxal phosphate
Reaction involved :
1/6/2017Namrata Chhabra, M.D., Biochemistry 11
12. Step-1- Reaction catalyzed by
Phosphorylase
Phosphorylase catalyzes the sequential removal of
glucosyl residues from the nonreducing ends of the
glycogen molecule (the ends with a free 4-OH group.
Orthophosphate splits the glycosidic linkage between
C-1 of the terminal residue and C-4 of the adjacent
one.
1/6/2017Namrata Chhabra, M.D., Biochemistry 12
14. Advantages of Phosphoroyltic cleavage
The phosphoroylytic cleavage of glycogen is energetically
advantageous because the released sugar is already
phosphorylated.
In contrast, a hydrolytic cleavage would yield glucose, which
would then have to be phosphorylated at the expense of the
hydrolysis of a molecule of ATP to enter the glycolytic pathway.
An additional advantage of phosphoroylytic cleavage for muscle
cells is that glucose 1-phosphate, negatively charged under
physiological conditions, cannot diffuse out of the cell.
1/6/2017Namrata Chhabra, M.D., Biochemistry 14
15. Problem with Phosphorylase
The α-1,6-glycosidic bonds at the branch points are
not susceptible to cleavage by phosphorylase.
Glycogen phosphorylase stops cleaving α -1,4
linkages when it reaches a terminal residue four
residues away from a branch point.
Because about 1 in 10 residues is branched, glycogen
degradation by the phosphorylase alone would come
to a halt after the release of six glucose molecules per
branch.
1/6/2017Namrata Chhabra, M.D., Biochemistry 15
16. Step-2- Remodeling and Debranching
Special Bifunctional
enzyme with two enzyme
activities
Transferase and
Debranching (α-1,6-
glucosidase)
Both these enzymes
remodel the glycogen for
continued degradation by
the phosphorylase.
1/6/2017Namrata Chhabra, M.D., Biochemistry 16
17. Role of Transferase
Transferase shifts a block of three glucosyl
residues from one outer branch to the other.
This transfer exposes a single glucose residue
joined by an α-1,6-glycosidic linkage.
Debranching enzyme, hydrolyzes the α -1, 6-
glycosidic bond, resulting in the release of a
free glucose molecule.
The transferase and α-1,6-glucosidase convert
the branched structure into a linear one,
which paves the way for further cleavage by
phosphorylase.
1/6/2017Namrata Chhabra, M.D., Biochemistry 17
18. Phosphorylase versus debranching
enzyme- Outcomes
Glucose-1-P is released as
an outcome of reaction
catalyzed by
Phosphorylase
Free glucose is released
by the action of
debranching enzyme
1/6/2017Namrata Chhabra, M.D., Biochemistry 18
19. Step-3- Conversion of Glucose-1-P to
Glucose-6-P
Phosphoglucomutase converts glucose 1-phosphate into glucose 6-
phosphate in a reversible reaction.
The catalytic site of an active mutase molecule contains a
phosphorylated serine residue.
The phosphoryl group is transferred from the serine residue to the
C-6 hydroxyl group of glucose 1-phosphate to form glucose 1,6-
bisphosphate.
The C-1 phosphoryl group of this intermediate is then shuttled to
the same serine residue, resulting in the formation of glucose 6-
phosphate and the regeneration of the phosphoenzyme.
1/6/2017Namrata Chhabra, M.D., Biochemistry 19
20. Reaction catalyzed by Phosphoglucomutase
1/6/2017Namrata Chhabra, M.D., Biochemistry 20
21. Step-4- Fate of Glucose-6-P
Glucose 6-phosphate derived from
glycogen can
(1) be used as a fuel for anaerobic or
aerobic metabolism as in, for instance,
muscle;
(2) be converted into free glucose in the
liver and subsequently released into the
blood;
(3) be processed by the pentose
phosphate pathway to generate NADPH or
ribose in a variety of tissues.
1/6/2017Namrata Chhabra, M.D., Biochemistry 21
22. The fate is different in liver and muscle
The liver contains a hydrolytic enzyme, glucose 6-phosphatase,
which cleaves the phosphoryl group to form free glucose and
orthophosphate.
Glucose 6-phosphatase is absent from most other tissues.
Consequently, glucose 6-phosphate is retained for the
generation of ATP.
In contrast, glucose is not a major fuel for the liver. The liver
releases glucose into the blood during muscular activity and
between meals to be taken up primarily by the brain and
skeletal muscle.
1/6/2017Namrata Chhabra, M.D., Biochemistry 22
24. Glycogenesis versus Glycogenolysis
• Glycogenolysis and
Glycogenesis are not
the just the reverse
of each other.
• The reaction
pathways, enzymes
and coenzymes are
all different and,
• both the ways are
reciprocally
regulated.
1/6/2017Namrata Chhabra, M.D., Biochemistry 24
25. Regulation of glycogen metabolism
To be continued in the next section…
1/6/2017Namrata Chhabra, M.D., Biochemistry 25