Nursing - 7

Glycogen metabolism

1

Glycogen metabolism Function of glycogen Glycogen is the storage form of carbohydrates in the human body.

The major sites of storage are liver and muscle.

1. The major function of liver glycogen is to provide glucose during starvation.

When blood glucose level lowers, liver glycogen is broken down and helps to maintain blood glucose level.

2. The function of muscle glycogen is to act as reserve fuel for muscle contraction.

Muscle glycogen is depleted after prolonged exercise.

2

After taking food, blood sugar tends to rise, which causes glycogen deposition in liver. About 5 hours after taking food, the blood sugar tends to fall. But, glycogen is lyzed to glucose so that the energy needs are met.

After about 18 hours fasting, most of the liver glycogen is depleted, when depot fats are hydrolyzed and energy requirement is met by fatty acid oxidation.

3

Glycogen metabolism includes:

Glycogenolysis.

Glycogenesis.

4

Glycogenolysis It is intracellular breakdown of glycogen to form

G-1-P which is converted to G-6-P.

Site and steps:

Its main site is the cytosol of liver and muscles.

It is catalyzed by: glycogen phosphorylase and two other

enzymes.

5

1- Glycogen phosphorylase: The enzyme glycogen phosphorylase

removes glucose units one at a time from the non-reducing end of the glycogen molecule.

The product is glucose-1-phosphate.

Phosphorylase sequentially attacks alpha-1,4 glycosidic linkages, till it reaches a branch point.

It cannot attack the 1,6 linkage at branch point.

6

7

2- Debranching needs two enzymes With the help of glucan transferase and

debranching enzyme (alpha-1,6- glucosidase), the branching point is also hydrolysed.

This glucose residue is released as free glucose.

With the removal of branch, phosphorylase enzyme can now proceed with its action.

8

9

3- Phosphoglucomutase: Phosphorylation reaction produces glucose-

1-phosphate while debrancher enzyme releases glucose.

The glucose-1-phosphate is converted to glucose-6-phosphate by phosphglucomutase.

10

4- Glucose-6-phosphatase in liver Next, hepatic glucose-6-phosphatase

hydrolyzed glucose-6-phosphate to glucose.

The product of hepatic glycogenolysis is free glucose.

The product of hepatic glycogenolysis is free glucose, which is released to the blood stream.

11

5- Muscle lacks Glucose-6-phosphatase: But muscle will not release glucose to the blood

stream, because muscle tissue doesnot contain the

Glucose-6-phosphatase.

The energy yield from one glucose residue derived

from glycogen is 3 ATP molecules, because no ATP

is required for initial phosphorylation of glucose

(step 1 of glycolysis).

If glycolysis starts from free glucose only 2 ATPs are

produced.

12

Glycogenesis

The glycogen synthesis occurs by a pathway distinctly

different from the reversal of glycogen breakdown.

It is the intracellular synthesis of glycogen from glucose.

Site and steps:

The main site is the cytosol of liver and muscle cells. In the

liver it forms 8-10% of its wet weight and in muscle it forms

1-2% of its wet weight. Most other cells may store minute

amounts.

13

1- Activation of Glucose: UDP glucose is formed from glucose-1-phosphate

and UTP (uridine triphosphate) by the catalytic activity of UDP-glucose pyrophosphorylase.

UDP-glucose-

pyrophosphorylase

Glucose-1- -------------------------------→ UDP-glucose

Phosphate

+ +

UTP PPi 14

2- Glycogen synthase: In the next step, activated glucose units are

sequentially added by the enzyme glycogen

synthase.

The glucose unit from UDP-glucose is transferred to

a glycogen primer molecule.

Glycogen primer (n)----------→ Glycogen (n+1)

+ +

UDP-glucose UDP 15

The glucose unit is added to the nonreducing (outer) end of the glycogen to form an alpha-1,4-glycosidic linkage and UDP is liberated.

The primer is essential as the acceptor of the glycosyl unit. The glycogen primer is formed by glycosylation of glycogenin (a dimeric protein).

This molecule acts as the glycogen primer to which glucose units are added by glycogen synthase.

16

3- Brancher enzyme A branching enzyme is needed to create

the alpha-1,6 linkages.

To this newly created branch, further

glucose units can be added in alpha-1,4

linkage by glycogen synthase.

Branching makes the molecule more

globular.

17

18

Regulation The key enzyme for glycogenolysis is

phosphorylase, which is activated by

glucagon and adrenaline, under the stimulus of

hypoglycemia.

The key enzyme for glycogen synthesis is

glycogen synthase, the activity of which is

decreased by adrenaline but is enhanced by

insulin, under the stimulus of hyperglycemia.

19

Glycogen storage diseases These are inborn-errors of metabolism; the

word is coined by Garrod in 1908.

Glycogen Storage Disease Type-I:

It is also called Von Gierke’s disease. Most common type of glycogen storage disease is type I.

20

Incidence is 1 in 100,000 live births.

Glucose-6-phosphatase is deficient.

Fasting hypoglycemia that does not respond to

stimulation by adrenaline. The glucose cannot be

released from the liver during over night fasting.

Hyperlipidemia, lactic acidosis and ketosis.

Glycogen gets deposited in liver. Massive liver

enlargement may lead to cirrhosis.

Children usually die in early childhood.

Treatment is to give small quantity of food at

frequent intervals. 21

Hexose Monophosphate pathway

(HMP)

or pentose phosphate pathway

(PPP)

or pentose pathway (shunt ) 22

23

24

25

26

27