ميحرلا نمحرلا للها مسب · this is the only system responsible for de novo...
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بسم اهلل الرحمن الرحيم
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Lipogenesis
Def.: the biosynthesis of triacylglycerol
principally from glucose.
Site: It occurs in most tissues especially adipose
tissue, liver, lactating mammary gland and
brain.
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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.
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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
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2-Biosynthesis of fatty acids:
From Glucose:
Glucoseglycolysis pyruvic
acid oxidative decarboxylation
acetyl-CoA (building block of fatty
acid synthesis).
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Intracellular site of FA synthesis
• Fatty acids synthesis may occur in the
following:
–Cytoplasmic (Extramitochondrial) FA
synthesis.
–Microsomal FA Synthesis.
–Mitochondrial FA synthesis
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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.
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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.
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Translocation of Acetyl-CoA from
mitocondria to cytoplasm
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Steps of Extramitochondrial
Pathway: 1. Synthesis of malonyl CoA
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1 2 3 4 5
6
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1 2 3 4 5
6
7
7 6 2 1
5 3
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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.
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Source of NADPH+H+
1. Hexose monophosphate shunt
2. Cytoplasmic isocitrate dehydrogenase
3. Malic enzyme.
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Fates of palmitate
1. Esterification
2. Chain elongation
3. Desaturation
4. Sphingosine formation
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Fates of palmitate
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Regulation of extramitochondrial FA synthesis
Rate-limiting and regulatory step
Acetyl CoA carboxylase
Acetyl Co A ------------------------------- Malonyl CoA
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Regulation
Short term regulation of acetyl CoA carboxylase.
Long term regulation
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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.
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Allostric regulation of Acetyl CoA carboxylase
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Covalent Modification of Acetyl CoA carboxylase
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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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