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

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

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 phosphorylated glycogen synthaseProtein kinase

ATP ADP (inactive)

Phophorylase phosphorylated phosphorylaseProtein kinase

ATP 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 Phosphorylase

Phosphatase

pi (inactive)

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.

Phosphorylated glycogen synthase glycogen synthase

Phosphatase

Pi (Active)

AMPphosphor diesterase

3,5 CAMPAdenyl Cyclase ATP

Difference between liver and muscle glycogen:

Liver glycogenMuscle glycogen

Source1-blood glucose2-other hexoses (fructose)3-non carbohydrate source e.g: Lactate

Blood glucose only

Amount120 gram350 gram

Conc.6%1%

FunctionIt maintain normal blood glucose conc. Between meals

Private source of energy for muscle only

End productsglucoseLactate due to absence of glucose-6-po4 in muscle

Effect of hormones1-Insulin2-Epinephrine3-Glucagon

Stimulate glycogenesesStimulate glycogenolysisStimulate glycogenolysis

SameSameNo effect

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