Fatty acid synthesis(Lipogenesis &

Lipolysis)

Introductionlipids are a good source of energy as 1

gm supplies 9.1 calories, which is over double that supplied by carbohydrates or protein.

Dietary lipids are ingested in form of

triglycerides, phosholipids, cholesterol and free fatty acids.

Lipids are esters of fatty acids with glycerol

called triglycerides because they are tri-

esters of glycerol

Lipogenesis It can be divided into 3 processes:

1)Biosynthesis of glycerol.2)Biosynthesis of fatty acids.3)Biosynthesis of the triacylglycerol.

It occurs in most tissues especially adipose tissue, liver, lactating mammary gland and brain.

Biosynthesis of glycerolGlucose is oxidized via glycolysis to dihydroxy acetone phosphate

reduced to glycerol-3 phosphate by the enzyme glycerol-3 phosphate dehydrogenase.

Biosynthesis of fatty acids

Glucose is oxidized via glycolysis to pyruvic which undergoes oxidative decarboxylation, forming

acetyl-CoA

(building block of fatty acid synthesis).

Cytoplasmic (Extramitochondrial) FA synthesis.

This is the only system responsible for

de novo synthesis of FA from active acetate.

Free palmitate is the main product.

Site: Many tissues, especially liver, kidney, brain,

lung, lactating mammary gland and adipose tissue.

Source of acetyl-CoA Acetyl-CoA, the main building block for FA

synthesis is formed from carbohydrate via oxidation of pyruvate within mitochondria.

Main requirements de novo synthesis of FA :

Acetyl CoA (Active Acetate) Acetyl CoA carboxylase Fatty acid synthase ATP & NADPH

I. Translocation of acetyl-CoA from mitochondria to cytoplasm

1) Step 1:Acetyl-CoA, formed from pyruvate within mitochondria, does not diffuse readily to cytoplasm (principle site for FA synthesis).

2) Step 2 :Translocation of acetyl CoA from mitochondria to the cytoplasm involves condensation with oxalacetate to form citrate which can pass out mitochondrial membrane.

II. In cytoplasm :

Step 3: citrate splits again by ATP

citrate lyase enzyme into acetyl-CoA and oxalacetate.

Step 4:

Acetyl CoA is converted to malonyl CoA, an important intermediate in fatty acid synthesis, by acetyl CoA carboxylase that consumes ATP and requires biotin as a cofactor.

Step 5: Condensation of Acetyl CoA and malonyl CoA

By

Fatty acid synthaseFatty acid synthase multienzyme complex. It is a dimer. Each unit contains 7 enzymes and a protein (acyl carrier protein)

Palmitate, a 16-carbon saturated fatty acid, is the final product of fatty acid synthesis.

Step 6: OAA is converted to malate.

Step 7: Malate is converted to pyruvate by malic

enzyme, producing 1 NADPH.a)NADPH is required for synthesis of

palmitate and elongation of fatty acids.

b)NADPH is produced in the cytosol by both malic enzyme and the pentose phosphate pathway, which is the primary source.

synthesis of palmitatePalmitate, a 16-carbon saturated fatty acid,

is the final product of fatty acid synthesis.

may be assembled in a repeating four-step

sequence

The first round of FA biosynthesis

To initiate FA biosynthesis, malonyl and acetyl groups are activated on to the enzyme fatty acid synthase.

Repetition of these four steps leads to fatty acid synthesis

When reaches 16 carbons, the product leaves the cycle.

All the reactions in the synthetic process are catalyzed by a multi-enzyme complex, fatty acid synthase.

Then the seven cycles of condensation and reduction produce the 16-carbon saturated palmitoyl group

Acetyl-CoA + 7malonyl-CoA + 14NADPH + 14H+ palmitate + 7CO2 + 8CoA + 14NADP+ +

6H2O

The biosynthesis of FAs requires acetyl-CoA and the input of energy in the form of ATP and reducing power of NADPH.

3-Biosynthesis of Triacylglycerols or fate of palmitate

Most of the fatty acids synthesized have one of two

fates: incorporation into triacylglycerols for the

storage of metabolic energy

or incorporation into the phospholipid

components of membranes.

Triacylglycerol is formed by estrification of 3

molecules fatty acids with one molecule of

glycerol-3 phosphate

LIPOLYSIS Adipose cells are specialized for synthesis

and storage of TG. LIPOLYSIS complete hydorlysis of

triglyceride yeild gelycerol and 3 fatty acids.

The hydrolysis of TG is done by 3 tissue lipases:

1. Hormone sensitive lipase initiates the process of lipolysis in the adipose tissue

2. Diacylglycerol lipase.3. Monoacylglycerol lipase.

• Diacylglycerol and monoacylglycerol lipases rapidly complete the hydrolysis of di and mono-acylglycerols releasing free fatty acids and glycerol

The activity of hormone sensitive lipase in the adipose cells is regulated by different hormones.

Glucagon, Epinephrine, norepinepherine hormones stimulate lipolysis

activate adenylate cyclase.

increased production of cAMP

activates protein Kinase A

subsequently activates lipases found in adipose tissue.

After lipolysis glycerol and free fatty acids

diffuse through the plasma membrane and enters the blood stream.