Transcript finalglycogen (2)

Glycogen metabolism
Glycogen is homopolysaccharide formed of branched α-DGLUCOSE units
(α1,4and α1,6)
each branch is made of 6-12 glucose units , at the branching
point the chain is attached by 1-6 link
site: present in cytoplasm of liver and muscles.•
Function of glycogen :
A) liver glycogen: it maintains normal blood glucose concentration in early
stage of fasting 12-18hours then is depleted
B) muscle glycogen : acts as source of energy within the muscle ,during
muscle contraction.
Definition* synthesis of glycogen (glycogenesis)
It is the formation of glycogen is liver and muscle.
Steps: glucose molecules are first activated to uridine diphosphate glucose
(UDP-6) then is added to glycogen primer to form glycogen.
Glucose
UTP
UDP-glucose
glycogen synthase
glycogen
UDP-glucose-
phosphoglucose mutase
G-6-Po4
glycogen primer
G-1-PO4
pyrophosphorylase
UDP-glucose
Formation of glycogen:
UDP-glucose reacts with glycogen primer .. glycogen synthase (key
enzyme) causing elongation of α1-4 branched up to 11 glucose
units
UDPG +glycogen primer
Glycogen synthase
UDP + elongated glycogen primer
Branching enzyme:
It transfers part of elongated chain (5-8glucose units) to the next
chain forming a new α1-6 glucosidic bond . The new branches are
elongated by glycogen synthase and the process is repeated .
Glycogenesis
Glucosen
+
UDP-Glucose
Preformed glycogen
Glucosen+1
+ UDP
Glycogen with one more glucose
 1-4 Glycosyl Linkage
UDP-Glysosyl transferase
I . Breakdown of glycogen (glycogenolsis)
Definition : it is a breakdown of glycogen into glucose in liver and lactic
acid in muscles.
Steps:
Phosphorylase (key enzyme): act on α(1-4bond) removes glucose units in
the form of glucose-1-P then the branch contains 4glucose unit, 3of them
are transferred to the next branch by transferase enzyme leaving the last
one.
Debranching enzyme: The last glucose units attacked to the original
branch by α 1-6 bond is removed by debranching enzyme then glucose-1PO4 are converted of G-6-Po4 by mutase. Then phosphatase give glucose.
Fat of glucose-6-Po4
In liver: it is converted to glucose by G-6-phosphotase.
In muscle: no G-6-phosphatase – So, glucose-6-PO4 enter glycolysis to
give lactate.
Regulation of glycogenesis and glycoenolysis
Conditions that stimulate glycogenolysis inhibit that of glycogenesis.
- During fasting: increase glycogenolysis and decrease
glyconeogensis so provid blood glucose.
- After meal: glycogensis is stimulated and glycogenolysis is
decreased
FASTING STATE
*Decrease blood glucose glycogenolysis is stimulated by
- CAMP and Protein kinase
- Ca++ and calmodulin protein `
*Decrease blood glocose → stimulate epinephrine and nor epinephrine and
glucagon.
*These hormones stimulate adenyl cyclase enzyme which convert
ATP → CAMP → stimulate protein kinase which cause phosphorylation to
both glycogen synthase and glycogen phosphorrylase.
Glycogen synthase
Protein kinase
ATP
phosphorylated glycogen synthase
ADP
(inactive)
Phophorylase
Protein kinase
ATP
phosphorylated phosphorylase
ADP
(active)
As a result glycogenolysis will proceed causing increase of blood
glucose at the same time glycogenesis will be inhibited.
AFTER MEAL:
Increase blood glucose level stimulate insulin.
Insulin causes :
-stimulate phosphodiestrase enzyme, convert CAMP to AMP so abolish the
stimulatory effect of CAMP so stimulation of phosphatase which decrease
phosphorylase and increase glycogen synthase so glycogenesis will proceed
and decrease glycogenolysis.`
Phosphorylated
Phosphorylase
Phosphatase
pi
Phosphorylase
(inactive)
Phosphorylated
glycogen synthase
Phosphatase
Pi
Adenyl Cyclase
ATP
glycogen synthase
(Active)
phosphor diesterase
3,5 CAMP
AMP
Glycogen storage disease:
there are group of inherited disorder cause deposition of abnormal quantity
of glycogen in tissues lead to deficiency of
glucose-6-phosphatase like.
Von-jierk's disease:
1- Accumulation of large amount of glycogen in liver , enlargement of it
increase liver enzyme, hepatomegaly, Fasting hypoglycemia, ketosis and
hyper lipidemia.
Difference between liver and muscle glycogen:
Liver glycogen
Muscle glycogen
Source
1-blood glucose
2-other hexoses (fructose)
3-non carbohydrate source e.g:
Lactate
Blood glucose only
Amount
120 gram
350 gram
Conc.
6%
1%
Function
It maintain normal blood
glucose conc. Between meals
Private source of
energy for muscle only
End products
glucose
Lactate due to absence
of glucose-6-po4 in
muscle
Effect of
hormones
1-Insulin
2-Epinephrine
3-Glucagon
Stimulate glycogeneses
Stimulate glycogenolysis
Stimulate glycogenolysis
Same
Same
No effect
Glconeogenesis
Definition :
Is a formation of glucose from non carbohydrate source they are:
1-lactate
2- pyruvate 3-glycerol
4-some amines acids
5-propinate
Function :
Supply body with glucose ( RBCs ,S.M)
Glucose give milk sugar (lactose)
When glycogen is depleted after 18 hours source of glucose
It clear the blood from waste product e.g. lactate and glycerol.
Location : cytosol and mitochondria of liver and kidney.
Organs : liver 90% , kidney 10%
Steps: reversal of glycolsis except the Three irreversible kinase which is replaced
by the following enzymes :
Glukokinase ≠glucose-6-phosphatease
Phosphofructo kinase ≠ fructose 1,6biophosphatase
Pyruvate kinase ≠ pyruvate carboxylase
* Phosphoenol pyruvate carboxy kinase
Pyruvate → oxaloacetate → malate (mitochondria) →
REP
x
oxaloacetate (cytoplasm) → phosphoenol pyruvate
Pathways for defferent sources of glyconeogenesis:
Any substance can join to common pathway of gluconeogenesis is
glycogenic
1)lactate is converted to pyruvate:
Lactate +NAD Lactate dehydrogenase
pyruvate + NAD+H
Pyruvate can join common pathway give glucose.
2) From glutamate
α-ketoglutarate → malate
α-ketoglutarate → succinyl COA → fumarate → malate (go to) →
cytoplasm
3) Propionic acid in ruminauts only
4) From glycerol from adipose tissue during fasting
2 molecules of glycerol → glucose
Regulation of gluconeogenesis:
Hormonal regulation
1. Gucocorticoids, cortisol stimulate: induce synthesis of
gluconeogenesis enzymes increase catabolism of protein give amino
acids increase process
2. Glucagon: decrease level of fructose-2,6-bisphosphate
3. Insulin: decrease gluconeogenesis decrease the three enzymes
4. Acetyl COA and ATP: increase by decrease glycolysis. Decrease
phsphofructokinase and increase gluconeogenesis by increase
fructose-1,6-bisphosphatase
•Acetyl COA increase pyruvate carboxylase and inhibit pyruvate
dehydrogenase