Title: Glycogen Metabolism
1Glycogen Metabolism
2Objectives
- Why do we need to store carbohydrates?
- Why carbohydrates are stored as glycogen?
- Overview of glycogen synthesis (Glycogenesis)
- Overview of glycogen breakdown (Glycogenolysis)
- Key elements in regulation of both Glycogenesis
- and Glycogenolysis
3 GLUCOSE
Pyruvate
Acetyl CoA
Citric Acid Cycle NADH FADH2
Electron transport chain
(flow of electrons) Formation of
ATP (oxidative phosphorylation)
HEXOSE MONOPHOSPHATE PATHWAY
GLYCOGEN SYNTHESIS
Ribose-5 Phosphate
Glycogen
NADPH
GLYCOLYSIS
No Oxygen No Mitochondria OR BOTH
Metabolism of Glucose
Lactate
Oxygen Mitochondria
4What do we really need?
- A constant source of glucose is mandatory for
- Brain
- Cells with few or no mitochondria
- Exercising muscles (anaerobic glycolysis)
5Sources of glucose to human body
-
- Glucose can be obtained from three primary
sources - Carbohydrate DIET
- - sporadic
- - depends on the diet (nature
amount) - - is not always a reliable source
of glucose - GLYCOGEN DEGRADATION (glycogenlysis from glycogen
stores) -
- GLUCONEOGENESIS (synthesis of glucose from non
carbohydrate sources) - - can provide sustained
synthesis of glucose - - BUT slow in responding to
blood glucose falling
6GLycogen
7GlycogenA storage form of glucose
8- Glycogen is stored in granules in the cytosol of
primarily the liver and skeletal muscles.
9Stores of Glycogen
- In skeletal muscle
- 1-2 of fresh weight of resting muscle ( 400 g)
- Depleted after prolonged vigorous exercise
- Moderately decreased by prolonged fasting (weeks)
- In liver
- 10 of the fresh weight in the well-fed adult
liver (100g) - After 12-18 hrs of fasting , almost depleted
10Thus
Liver glycogen is used to buffer the overall
blood glucose level glycogen is degraded
(with the resulting glucose released into the
blood stream) during the early stages of a fast.
Muscle uses its glycogen stores for (ATP)
energy during strenuous exercise.
11Structure of Glycogen
12 It is a highly branched chain
homopolysaccharide made from a-D glucose .
13- Amylose is the linear unbranched molecule of
glucosyl residues attached by a(1?4) linkages. - Glycogen has branches located on average eight
glucosyl residues resulting in highly branched
molecule which leads to - More soluble
- Increase rate of degradation
- Increase rate of synthesis
14Metabolism of Glycogen in Skeletal Muscle
- Glycogenesis
- Synthesis of Glycogen from Glucose
- Glycogenolysis
- Breakdown of Glycogen to Glucose-6-phosphate
15Glycogen Synthesis (Glycogenesis)
16- Site cytosol
- It requires UTP
- 1- Building blocks UDP-GLUCOSE
- 2- Initiation of synthesis
- Elongation of pre-existing glycogen fragment
- OR
- The use of a protein glycogen primer
(glycogenin) - (Glycogen synthase cannot initiate synthesis but
only elongates pre-existing glycogen fragment or
glycogen primer (glycogenin) - 3- ELONGATION Glycogen synthase (for a1-4
linkages) - 4- BRANCHING Branching enzyme (for a1-6
linkages
17(No Transcript)
18(No Transcript)
19Glycogen BreakdownGlycogenolysis
201- Shortening of glycogen chain phosphorylase
Cleaving of a(1-4) bonds of the glycogen chain
producing glucose 1-phosphate Glucose
1-phosphate is converted to glucose 6-phosphate
(by mutase enzyme)
Pyridoxal phosphate (vit -B6
21- 2- Removal of branches by debranching enzymes
- Cleaving of a(1-6) bonds of the glycogen chain
producing free glucose (few) - 3- Fate of glucose 6-phosphate (G-6-P)
- - G-6-P is not converted to free glucose
- - It is used as a source of energy for
skeletal muscles during muscular exercise (by
anaerobic glycolysis starting from G-6-P step) -
- ( in case of liver glucose-6-phosphatase converts
G6P to glucose
22glycogenlysis
23(No Transcript)
24(No Transcript)
25Regulation
26Regulation of Glycogen Metabolism
- Synthesis degradation of glycogen are tightly
regulated - In the liver
- Glycogen degradation accelerates during fasting
- Glycogen synthesis accelerates during well-fed
status - In Skeletal Muscles
- Glycogen degradation occurs during active
exercise - Glycogen synthesis begins when the muscle is at
rest - Regulation occurs by 2 mechanisms
1- Allosteric regulation 2- Hormonal
regulation (Covalent modification)
27Regulation of Glycogen Metabolism 1. Allosteric
Regulation
28(No Transcript)
29Regulation of Glycogen Metabolism
Increase of calcium during muscle
contraction Formation of Ca2 -calmodulin
complex Activation of Ca2 -dependent enzymes,
e.g., glycogen phosphorylase
30Regulation of Glycogen Metabolism 2. Hormonal
Regulation by Epinephrine
31(No Transcript)
32Glycogen Storage DiseasesGSD Type V (Mc Ardle
Syndrome)
- Deficiency of skeletal muscle glycogen
phosphorylase
33