بسم اهلل الرحمن الرحيم

Lipogenesis

Def.: the biosynthesis of triacylglycerol

principally from glucose.

Site: It occurs in most tissues especially adipose

tissue, liver, lactating mammary gland and

brain.

Lipogenesis

Function: storage of excess glucose after a

carbohydrate rich meal.

Steps: It can be divided into 3 processes:

Biosynthesis of glycerol 3 phosphate.

Biosynthesis of fatty acids.

Biosynthesis of the triacylglycerol.

1-Biosynthesis of glycerol 3

phosphate:

C H2 OH C H2 OH

Glucose------ C = O --------- C H OH

C H2 OP C H2 OP DHAP Glycerol 3- phosphate

Glycolysis

Glycerol

3- phosphate

dehydrogenase

2-Biosynthesis of fatty acids:

From Glucose:

Glucoseglycolysis pyruvic

acid oxidative decarboxylation

acetyl-CoA (building block of fatty

acid synthesis).

Intracellular site of FA synthesis

• Fatty acids synthesis may occur in the

following:

–Cytoplasmic (Extramitochondrial) FA

synthesis.

–Microsomal FA Synthesis.

–Mitochondrial FA synthesis

Extramitochondrial FA Synthesis

Cytoplasmic, Lynen Cycle

This is the only system responsible for de novo synthesis of FA from active acetate.

Free palmitate is the main product.

Extramitochondrial FA Synthesis

Cytoplasmic, Lynen Cycle

• Site: many tissues, especially adipose tissue, liver,

lactating mammary gland and brain.

• Source of acetyl-CoA:

• main building block for FA synthesis

• from carbohydrate via oxidation of pyruvic within

mitochondria.

Translocation of Acetyl-CoA from

mitocondria to cytoplasm

Steps of Extramitochondrial

Pathway: 1. Synthesis of malonyl CoA

1 2 3 4 5

6

7

1 2 3 4 5

6

7

7 6 2 1

5 3

4

7

Steps of Extramitochondrial

Pathway:

2. Synthesis of palmitate

CH3CO~ CoA + 7 HOOC.CH2CO~ S CoA + 14 NADPH+H+

CH3 (CH2)14COOH + 7CO2+ 8 CoA ~ SH+ 6H2O+ 14 NADP.

Source of NADPH+H+

1. Hexose monophosphate shunt

2. Cytoplasmic isocitrate dehydrogenase

3. Malic enzyme.

Fates of palmitate

1. Esterification

2. Chain elongation

3. Desaturation

4. Sphingosine formation

Fates of palmitate

Regulation of extramitochondrial FA synthesis

Rate-limiting and regulatory step

Acetyl CoA carboxylase

Acetyl Co A ------------------------------- Malonyl CoA

Regulation

Short term regulation of acetyl CoA carboxylase.

Long term regulation

Short term regulation

1. Allosteric Regulation:

The inactive form of acetyl CoA carboxylase is a protomer (dimer).

• Allosteric activation by citrate which cause dimmers to polymerize.

• Allosterically inactivation by long chain fatty acid (The end product of the pathway).

2. covalent modification (reversible phosphorylation):

• Epinephrine and glucagon phosphorylation of acetyl. CoA carboxylase inactivation.

• Insulin dephosphorylation of acetyl. CoA carboxylase activation.

Allostric regulation of Acetyl CoA carboxylase

Covalent Modification of Acetyl CoA carboxylase

Long term regulation

• prolonged consumption of a diet contain excess

calories (high carbohydrate diet increase in

acetyl CoA carboxylase synthesis increasing

fatty acid synthesis.

• Low calorie diet or fasting decreasing the

synthesis of acetyl CoA carboxylase reduction

in FA synthesis.