very new glucogen me..

Download Report

Transcript very new glucogen me..

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
1-6 Glycosyl linkage
Glycogenolysis
Provides glucose.
2 steps:
Hydrolysis of 
glycosidic bond
by glycogenphosphorylase
Debranching 
enzyme.
Glycogen phosphorylase
Pi
Debranching Enzyme
[Glucosyltransferase]
Debranching Enzyme
H2O
[Glucosidase]
Glycogen phosphorylase
Pi
Pi
1-4 Glycosyl linkage
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
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.
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
Role of insulin in lowering blood glucose level
Muscle
 Glucose uptake
 Blood
glucose
 Glycogen synthesis
Liver
 Glucose metabolism
 Glycogen synthesis
 Glycolysis
 Gluconeogenesis
+
+
 FA synthesis
+
Pancreas
Beta cells
 TG synthesis
Insulin
secretion
 VLDL synthesis
+
 Glucose uptake
 FA uptake
 TG synthesis
Adipose tissues
VLDL
Role of Liver in controlling blood glucose level
- Insulin not needed for uptake of glucose
by liver
- Insulin is needed for uptake of glucose
by other tissues
 uptake
Liver
Glycogen
Lactate
Amino acid
Glycerol
 Blood glucose
Glucose
 Glucose synthesis
(gluconeogenesis)
 blood glucose
Glycogen breakdown
to  blood glucose
Other
Tissue
s
Glucose is
metabolised
 Blood glucose