glycogen synthesis (or glycogenesis)
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Glycogen Synthesis (or Glycogenesis)
Definition:It is the formation of glycogen, which occurs in all tissues of the body, but in large amount in liver and muscles. There are very small amount of glycogen synthesis and storage in the central nervous system; this is why it is completely dependent on blood glucose as a source of energy.Site:Cytosol of all cells particularly liver and muscles.
Sources of glucose:A-For liver glycogen:•Blood glucose•Other hexoses: fructose and galactose•Non-carbohydrate sources: “gluconeogenesis”, e.g., amino acids, glycerol and lactate during fed state.
B-For muscle glycogen: •blood glucose only.
The Sugar Nucleotide UDP-Glucose Donates Glucosefor Glycogen Synthesis
Regulation of Glycogen Synthesis
Protein Kinase(s) Glycogen synthase D(Inactive)
(or b, or Phospho) ADPATPMg+2
H2OPi
Synthase Phosphatase
Adrenaline, Glucagon, Thyroxine
ATP cAMP AMP
cAMP- phosphodiesterase
Insulin
++Adenylate Cyclase
+
Insulin+
Glucos-6-phosphate
+
Glycogen
-
-Phosphatase
Inhibitor-IcAMP +
Glycogen synthase I(Active)
(or a, or Dephospho)
Glycogen Breakdown (or Glycogenolysis)
Definition:Definition:
It is the process of glycogen catabolism (or breakdown) into:
Glucose to blood, in the liver. Or,
Glucose-6-phosphate Lactic acid, in the muscles.
Site: Site:
Cytosol of all cells but high activity in liver and muscles.
Glucose-6-phosphate
Phosphoglucomutase
Glucose-1-phosphate
OH
OH
H
OHH
OHH
OH
CH 2O-P
H
OH
OH
H
H
OHH
OH
CH 2OH
H
O-P
OH H
O
OHH
OH
CH 2OH
H14
OH
OH
H
OHH
OH
CH 2OH
H14
O
Pi
OH
OH
H
O
OHH
OH
CH 2OH
H14+
GlycogenPhosphorylase
Glucose
OH
OH
H
OHH
OHH
OH
CH 2OH
HH2O Pi
Phosphatasein liver, ONLY
PLP
GlycogenCore, n
Glycogen Core, n -1
OH H
H
OHH
OH
CH2OH
H
O
OH H
H
OHH
OH
CH2
HOH H
OH
OHH
OH
CH2OH
H
OO
O
OH
OH
H
H
OHH
OH
CH2OH
H1
6
1 1 1
4
4 44
OH H
H
OHH
OH
CH2OH
H
O
OH H
H
OHH
OH
CH2OH
HOH H
OH
OHH
OH
CH2OH
H
OO1 1 14 44
H2O
GlucoseOH
OH
H
OHH
OHH
OH
CH2OH
HDebranching
Enzyme
Glycogen
Core, n
Glycogen
Core, n - 1
Regulation of Glycogenolysis
Phosphrylase b Kinase
ADPATPMg+2
H2OPi
Phosphatase
Adrenaline, Glucagon
ATP cAMP AMP
cAMP- phosphodiesterase
Insulin
++
Adenylate Cyclase
+
Insulin+
GlucoseAMP
-cAMP
-+
Glucose-6-phosphate, ATP
-
+
Inactive cAMP-dependent
Protein Kinase
Active cAMP-dependent
Protein Kinase +
Ca+2
Neuromuscular excitation,Adrenaline
Glycogen Phosphrylase a
(Active or Phospho)
Glycogen Phosphrylase b
(Inactive or Dephospho)
Glycogen Storage Diseases
Definition:Glycogen storage diseases are groups of inherited disorders characterized by deposition (over-storage) of an abnormal type or quantity of glycogen or failure of storage of glycogen in the tissues.They are mainly due to deficiency of one of enzymes of glycogenesis or glycogenolysis, phosphofructokinase, or lysosomal glycosidases.
1-Type I: Von Gierke’s disease:2-Type II: (Pompe’s disease):3-Type III: (Limit Dextrinosis, Forbe's disease):4-Type IV: (Andersen’s disease):5-Type V: (McArdle’s disease):6-Type VI: (Hers' disease):7-Type VII: (Tarui’s disease):8-Type VIII:
Gluconeogenesis
Is the formation of glucose from non-carbohydrate precursors. It is particularly important for tissues dependent on blood glucose such as RBCs and brain. The daily glucose requirements of the adult brain is 120 grams, whereas, the whole body requires 160 grams. The body stores are 210 grams (190 grams from liver glycogen and 20 grams in body fluids) enough for a day.
In a longer period of starvation, glucose must be formed from non-carbohydrate sources for survival. It also occurs during intense exercise. These non-carbohydrate precursors include lactate, pyruvate, propionate, glycerol (from diet and lipolysis) and glucogenic amino acids.
Site: Mitochondria and cytosol of Liver and kidney are almost the only organs able to synthesize glucose from non-carbohydrate sources.
Gluconeogenesis from Glycerol
• Glycerol absorbed from diet or derived from lipolysis of fat is activated by glycerol kinase in liver, kidney, lactating mammary gland, heart and intestine into glyerol-3-phosphate.
• Glyerol-3-phosphate dehydrogenase oxidizes glyerol-3-phosphate into dihydroxyacetone-phosphate to cross glycolysis into glucose
CH - OH
CH 2 OH
Glycerol
CH 2 OH CH-OHCH 2 O
Glycerol-3-phosphate
CH 2 OH
POH
OHO C
CH 2 O
CH 2 OH
Dihydroxyacetone phosphate
ONAD NADH.H+
Glycerol-3-phosphate
Dehydrogenase
AT P ADP
Glycerokinase P OH
OH
O
Gluconeogenesis from Propionic Acid • Propionic acid is derived from, methionine, isoleucine,
-oxidation of odd number fatty acid, cholesterol conversion into bile acids and large intestinal and ruminal fermentation of fibers
• Microfloral fermentation of dietary fibers in human large intestine and rumen of ruminants produces volatile fatty acids (Propionic, acetic and butyric acids).
• Propionic acid is the major source of glucose synthesized by gluconeogenesis in ruminants.
CH 3 CH 2 C OH
OCH 3 CH 2 C SC oA
O
CoASHATP
CH 3 CH C SC oA
O
COO H
Mg+2
Propionyl-CoA Synthetase CO 2+ ATP
Propionyl-CoACarboxylase
D-Methyl malonyl-CoA
CH 2 C SC oA
O
CH 2 COO H
B12Methyl
malonyl-CoAIsomerase Succinyl-CoA
Propionic acid
ADP + Pi
CH 3 CH C SC oA
OCOO H
L-Methyl malonyl-CoA
Biotin
Methyl malonyl-CoA
Racemase
Propionyl-CoA
AMP +PPi
Gluconeogenesis from glucogenic amino acids
Gluconeogenesis from Lactate and Pyruvate(Cori's Cycle)
• Cori's Cycle is the cycle illustrating the fate of lactic acid produced by active muscles and RBCs.
• Lactate and/or pyruvate formed by the anaerobic oxidation of glucose from skeletal muscle glycogen or glycolysis in RBCs, diffuses to blood stream and is transported to the liver and the kidney where it is transformed into glucose by gluconeogenesis
• Pyruvate also leaves muscles as alanine after transamination particularly during long starvation, where muscle proteins break down.
• Alanine goes to liver where transamination converts it back into pyruvate.
• The glucose formed diffuses back to the blood to be used by various tissues.
Blood
Glucose GlucoseGlucose
GlycogenPyruvate
Lactate
Glucose-6-phosphateGlucose-6-phosphate
Glycogen Pyruvate
Lactate Lactate
Pyruvate
AlanineAlanineAlanine
Thank You Thank You
Edited byEdited byDr/Ali H. El-FarDr/Ali H. El-Far
Lecturer of BiochemistryLecturer of BiochemistryFac. of Vet. Med.Fac. of Vet. Med.Damanhour Univ.Damanhour Univ.
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