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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.
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