Glycogen metabolism. Glycogen is homopolysaccharide formed of branched α-D- GLUCOSE units (α1,4and...

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Glycogen metabolism

Transcript of Glycogen metabolism. Glycogen is homopolysaccharide formed of branched α-D- GLUCOSE units (α1,4and...

Glycogen metabolism

Glycogen is homopolysaccharide formed of branched α-D-GLUCOSE 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.

GlucoseUTP

UDP-glucoseglycogen primer

glycogenglycogen synthase

G-6-Po4 phosphoglucose mutase

G-1-PO4

UDP-glucose-

UDP-glucose pyrophosphorylase

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 primerGlycogen 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+ Glucosen+1 + UDP

Preformed glycogen Glycogen with one more glucose

UDP-Glysosyl transferase

1-4 Glycosyl Linkage

Glycogenolysis

Provides glucose.2 steps:

Hydrolysis of glycosidic bond

by glycogen-phosphorylase

Debranching enzyme.

Pi

1-6 Glycosyl linkage

1-4 Glycosyl linkageGlycogen phosphorylase

Debranching Enzyme[Glucosyltransferase]

Debranching Enzyme[Glucosidase]

Glycogen phosphorylase

Pi

H2O

Pi

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-1-

PO4 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.

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 glucoseIt clear the blood from waste product e.g. lactate and glycerol.

Glconeogenesis

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 1,6biophosphatasePyruvate 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 fasting2 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

VLDL

Insulin secretionBeta cells

Pancreas

Blood glucose

Glucose uptake

Glycogen synthesis

Glucose metabolism Glycogen synthesis

Glycolysis Gluconeogenesis

FA synthesis

TG synthesis

VLDL synthesis

Glucose uptake

FA uptake

TG synthesis

Adipose tissues

Muscle

Liver

++

+

+

Role of Liver in controlling blood glucose level

Blood glucose

Blood glucose

Liver

-Insulin not needed for uptake of glucose by liver

-Insulin is needed for uptake of glucose by other tissues

uptake

Glycogen Glucose

Glycogen breakdown to blood glucose

Glucose synthesis(gluconeogenesis)

blood glucose LactateAmino acid

Glycerol

Other Tissue

s

Glucose is metabolised