Transcript Overview of metabolism

Glycogen Synthesis (or
Glycogenesis)
http://www.youtube.com/watch?v=h6qgfpinOyY
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 Glucose
for Glycogen Synthesis
Regulation of Glycogen Synthesis
Adrenaline, Glucagon, Thyroxine
Insulin
+
+
Adenyl a teCycl ase
ATP
cAMP
cAMPphosphodiesterase
AMP
+
Glycogen synthase I
(Active)
(or a, or Dephospho)
-
Protein Kinase(s)
Mg+2
ATP
ADP
Synthase Phosphatase
Glycoge n
+
Glucos -6-phosphate
Pi
cAMP
Glycogen synthase D
(Inactive)
(or b, or Phospho)
+
-
Phosphatase
Inhibitor-I
H2O
+
Insulin
Glycogen Breakdown (or
Glycogenolysis)
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:
Cytosol of all cells but high activity in liver and
muscles.
CH 2OH
O
H
OH
H
4
OH
H
H
H
1
4
O
CH 2OH
O
H
OH
H
OH
H
1
O
OH
Glycoge n
Cor e, n
Glycogen
Phosphorylase
Pi
PLP
H
OH
CH 2OH
O
H
H
OH
H
H
H
+
O-P
4
OH
OH
CH 2OH
O
H
OH
H
H
1
O
OH
Glycoge n
Cor e, n -1
Glucose-1-phosphate
Phosphoglucomutase
H
CH 2O-P
O
H
H
OH
H
H2O
Pi
Phosphatase
in liver, ONLY
H
OH
Glucose-6-phosphate
OH
OH
H
OH
CH 2OH
O
H
H
OH
H
OH
Glucose
H
OH
H
4
OH
H
4
O
CH2OH
O
H
OH H
H
CH2OH
O
H
OH H
H
H
1
O
H
1
O
OH
6CH2
O
H
H
4
OH H
H
OH
H
H
1 4
O
CH2OH
O
H
OH H
H
OH
H2O
H
Debranching
Enzyme
OH
H
4
O
H
OH
H
1
H
4
O
CH2OH
O
H
OH H
H
OH
H
1
O
H
4
OH
CH2OH
O
H
H
OH
H
CH2OH
O
H
OH H
H
1
O
H
Glucose
OH
OH
CH2OH
O
H
OH H
H
Glycoge n
Core, n
OH
H
1
O
Glycoge n
Core, n - 1
Regulation of Glycogenolysis
Adrenaline, Glucagon
Insulin
+
+
Adenyl a teCycl ase
ATP
Inactive cAMPdependent
Protein Kinase
cAMP
+
cAMPphosphodiesterase
Active cAMPdependent
Protein Kinase
+
Glycogen
Phosphrylase b
(Inactive or Dephospho)
+
-
Neuromuscular
excitation,
Adrenaline
Phosphrylase b
Kinase
ATP
Mg+2
ADP
Phosphatase
AMP
Glucos e-6-phosphate,
ATP
Pi
-
cAMP
H2O
+
Insulin
AMP
Ca+2
+
Glycogen
Phosphrylase a
(Active or Phospho)
Glucos e
http://www.youtube.com/watch?v=h6qgfpinOyY
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 dihydroxyacetonephosphate to cross glycolysis into glucose
CH2 OH
CH - OH
Glycerokinase
CH2 OH
Glycerol
ATP
ADP
+ CH2 OH
CH2 OH
NAD NADH.H
O
C O
CH-OH O
CH2 O P OH
CH2 O P OH
Glycerol-3OH
OH
phosphate Dihydroxyacetone
Glycerol-3phosphate
phosphate Dehydrogenase
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.
CoASH
ATP
O
CH3 CH2
C
Mg+2
OH
Propionic acid
AMP+PPi
Propionyl-CoA
Synthetase
O
CH3 CH2
COOH O
CH3 CH
C SCoA
L-Methyl malonyl-CoA
B12
Methyl
malonyl-CoA
Isomerase
SCoA
Propionyl-CoA
CO 2+ ATP
Biotin
Methyl
malonyl-CoA
Racemase
C
Propionyl-CoA
Carboxylase
ADP + Pi
O
CH3 CH
C
SCoA
COOH
D-Me thyl malonyl-CoA
O
CH2
C
SCoA
CH2
COOH
Succinyl-CoA
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.
Glucose
Glucose
Glucose-6-phosphate
Glucose
Glucose-6-phosphate
Glycogen Pyruvate
Pyruvate
Pyruvate
Lactate
Lactate
Alanine
Lactate
Alanine
Blood
Glycogen
Alanine
Thank You
Edited by
Dr/Ali H. El-Far
Lecturer of Biochemistry
Fac. of Vet. Med.
Damanhour Univ.