Lipogenesis

Fats not only obtained from the diet but also obtained from lipogenesis in the body. Lipogenesis means synthesis of fats from CHO and proteins present in excess of body need.

Lipogenesis requires: 1- Synthesis of fatty acids (FA) and glycerol2- Activation of fatty acids by CoA and glycerol by glycerokinase, 3- Combination of activated fatty acid and glycerol to give TAG (fats).

De no vo synthesis of fatty acid (cytoplasmic synthesis):

Occur mainly for the synthesis of palmitic acid

Site: Cytoplasm of liver, mammary glands and adipose tissues.

Steps: 1- Transport of acetyl CoA to cytoplasm: Acetyl CoA is the precursor

of fatty acid synthesis. It is produced from oxidation of glucose (by oxidative decarboxylation of pyruvate) and metabolism of ketogenic and mixed amino acids.

Acetyl CoA is produced in mitochondria, and FA synthesis occurs in cytoplasm, so acetyl CoA must be transferred to cytoplasm across mitochondrial membrane which is impermeable to CoA. The transport occur through condensation of acetyl CoA inside mitochondria with oxaloacetate (OAA) to form citrate which can be transferred into cytoplasm. In cytoplasm, citrate is cleaved by ATP-citrate lyase or called citrate cleavage system in the presence of ATP and CoA to give acetyl CoA and OAA.

Transport of acetyl CoA from mitochondria to cytoplasm:

Mitochondria:

OAA + Acetyl CoA

-CoA ↓ citrate synthase

Citrate

Inner mitochondrial membrane ↓ Citrate

+ CoA, ATP ↓ ATP citrate lyase

OAA + Acetyl CoACystosol

2-Conversion of acetyl CoA into malonyl CoA by acetyl CoA carboxylase

This step is the rate limiting step in FA synthesis and acetyl CoA carboxylase is the rate limiting enzyme.

3- Remaining series of the pathway is catalyzed by fatty acid synthase which is a multifunctional enzyme.

Reaction catalyzed by Acetyl CoA Carboxylase

For illustration only

Regulation of acetyl CoA carboxylase:

A)Allosteric regulation: allosterically activated by citrate & ATP and

inhibited by the end product of the pathway (palmitic acid).

B)B) Hormonal regulation: activated by insulin, inhibited by

adrenaline and glucagon (anti-insulin hormone).

C) Dietary regulation: prolonged consumption of high claoric diet (e.g

CHO diet) increases the synthesis of acetyl CoA carboxylase and so

increase FA synthesis. Fat-free diet, fasting and low CHO reduce

enzyme synthesis and so FA synthesis.

Elongation of fatty acids: Mitochondrial synthesis

Palmitic acid - the end product of FA synthesis in cytoplasm

can be elongated in mitochondria by the addition of two carbon

atoms to give other long chain saturated FA e.g. stearic acid

Unsaturation: occur also in mitochondria by desaturase enzyme

to give unsaturated fatty acids e.g. oleic acid

Biosynthesis of TAG from synthesized fatty acid and glycerol:

Site: cytoplasm of liver and adipose tissues

Steps: see figure

1- Activation of fatty acids into acyl CoA

2- Activation of glycerol into 3-glycerophosphate

3-Combination of activated fatty acid and glycerol to form DAG then TAG as in figure.

A)

CH2-OH

CH-OH

CH2-OH

Glycerol

glycerokinaseATP

ADP

CH2-OH

CH-OH

CH2-O-PO3

3-glycerophosphate

B)

2RCOOH

Fattyacid

2CoASH

thiokinase

2RC-SCoA

O

- 2CoA

CH2-O-CO-R1

CH-O-CO-R2

CH2-O-PO3

Phosphatidic acid

Phosphatase

pi

CH2O-CO-R1

CH2-O-H

CH2O-CH3O-R2

1,2 diacylglycerol (DAG)

CDP-choline

Lecithicin

Acyl CoA, acyl transferase

TAG

Synthesis of TAG (for illustration)

Comparison between de novo synthesis and degradation (β-oxidation) of long chain saturated fatty acids:

Lioplysis (fatty acid β-oxidation

Lipogenesis (fatty acid synthesis)

Definition Degradation of depot fat (release of FFA from

stored TAG, then oxidized to give energy fat)

Synthesis of fat (triglycerides) from CHO and protein that exceed the body need

Greatest flux of pathway (diet regulation)Hormonal state that favor pathway

Major tissue site (organ)

Tissue location for fatty acid synthesis or degradationTwo-carbon donor/product

Allosteric ActivatorAllosteric Inhibitor

Carrier of acyl/acetyl groups between mitochondria and cytosol

H-carrierNB: the synthesis of TAG occurs mainly in liver and mammary glands but it is stored mainly in adipose tissue and muscles

Types of body fat 

Depot fat (stored fat) It is a fat stored in the fat cells of adipose tissues. The amount and composition of depot fat varies according to the nutritional state of the individuals so it is called variable elements. Source: The origin of depot fat is dietary fat and lipogenesis.Composition: Triglycerides mainlyFate: Source of energy for body by first lipolysis (release of fatty acids from fats) by hormone sensitive lipase (HSL) which is inhibited by insulin and activated by adrenaline and glucagon.

Tissue fat (constant element) Def. It is the fat present in each cell. It is the lipids that enter in the structure of body cells as cell membrane and mitochondria. It is not affected by hormones.It is never used as source of energy i.e. never oxidized to give energy.  

Depot fat Tissue fat

It is the fat stored in fat cells of adipose tissue. This fat derived from dietary fat and lipogenesis

It is the fat that enter in the structure of cell membranes

Variable element Constant element

Present in certain tissues as liver and adipose tissues under the skin, around certain organs as kidney

Present in every cells

Formed mainly from triglycerides Formed mainly of cholesterol, phospholipids and glycolipids

Affected by hormones (How?) Not affected by hormones

Used in starvation Not used

Functions: source of energy, protection and insulator of heat, fixation of certain organs as kidney

Enter in the structure of cell membraneNever used as source of energy.