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Fatty acid synthesis ( Lipogenesis & Lipolysis )

Fatty acid synthesis ( Lipogenesis & Lipolysis ). Introduction lipids 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

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Fatty acid synthesis ( Lipogenesis & Lipolysis )

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  1. Fatty acid synthesis(Lipogenesis &Lipolysis)

  2. Introduction • lipids are a good source of energy as 1 gm supplies 9.1 calories, which is over double that supplied by carbohydrates or protein. • Dietary lipidsare ingested in form of triglycerides,phosholipids,cholesterol and free fatty acids.

  3. Lipids are esters of fatty acids with glycerol called triglyceridesbecause they are tri-esters of glycerol

  4. Lipogenesis • It can be divided into 3 processes: • Biosynthesis of glycerol. • Biosynthesis of fatty acids. • Biosynthesis of the triacylglycerol. • It occurs in most tissues especially adipose tissue, liver, lactating mammary gland and brain.

  5. Biosynthesis of glycerol • Glucose is oxidized via glycolysis to dihydroxy acetone phosphate reduced to glycerol-3 phosphate by the enzyme glycerol-3 phosphate dehydrogenase.

  6. Biosynthesis of fatty acids • Glucose is oxidized via glycolysis to pyruvic which undergoes oxidative decarboxylation, forming acetyl-CoA (building block of fatty acid synthesis).

  7. 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.

  8. 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 pyruvatewithin mitochondria.

  9. Main requirements de novo synthesis of FA : • Acetyl CoA (Active Acetate) • Acetyl CoAcarboxylase • Fatty acid synthase • ATP & NADPH

  10. I. Translocation of acetyl-CoA from mitochondria to cytoplasm • Step 1:Acetyl-CoA, formed from pyruvate within mitochondria, does not diffuse readily to cytoplasm (principle site for FA synthesis). • Step 2 :Translocation of acetyl CoAfrom mitochondria to the cytoplasm involves condensation with oxalacetate to form citrate which can pass out mitochondrial membrane.

  11. II. In cytoplasm : Step 3: citrate splits again by ATP citrate lyaseenzyme into acetyl-CoAandoxalacetate.

  12. Step 4: Acetyl CoAis converted to malonylCoA, an important intermediate in fatty acid synthesis, by acetyl CoAcarboxylasethat consumes ATP and requires biotin as a cofactor.

  13. Step 5: Condensation of Acetyl CoAand malonylCoA By Fatty acid synthase Fatty acid synthasemultienzyme 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.

  14. Step 6: OAA is converted to malate. Step 7: Malate is converted to pyruvateby malic enzyme, producing 1 NADPH. • NADPH is required for synthesis of palmitate and elongation of fatty acids. • NADPH is produced in the cytosol by both malic enzyme and the pentose phosphate pathway, which is the primary source.

  15. synthesis of palmitate Palmitate, a 16-carbon saturated fatty acid, is the final product of fatty acid synthesis. may be assembledin a repeating four-step sequence

  16. The first round of FA biosynthesis • To initiate FA biosynthesis, malonyl and acetyl groups are activated on to the enzyme fatty acid synthase.

  17. 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.

  18. Then the seven cycles of condensation and reductionproduce the 16-carbon saturated palmitoyl group Acetyl-CoA + 7malonyl-CoA + 14NADPH + 14H+ palmitate + 7CO2 + 8CoA + 14NADP+ + 6H2O • The biosynthesis of FAs requires acetyl-CoAand the input of energy in the form of ATP and reducing power of NADPH.

  19. 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. • Triacylglycerolis formed by estrification of 3 molecules fatty acids with one molecule of glycerol-3 phosphate

  20. LIPOLYSIS • Adipose cells are specialized for synthesis and storage of TG. • LIPOLYSIS complete hydorlysis of triglyceride yeild gelycerol and 3 fatty acids.

  21. The hydrolysis of TGis done by 3 tissue lipases: • Hormone sensitive lipase initiates the process of lipolysis in the adipose tissue • Diacylglycerol lipase. • Monoacylglycerol lipase. • Diacylglycerol and monoacylglycerol lipases rapidly complete the hydrolysis of di and mono-acylglycerols releasing free fatty acids and glycerol

  22. The activity of hormone sensitive lipase in the adipose cells is regulated by different hormones. • Glucagon, Epinephrine, norepinepherinehormones stimulate lipolysis activate adenylatecyclase. increased production of cAMP activates protein Kinase A subsequently activates lipases found in adipose tissue.

  23. After lipolysis glycerol and free fatty acids diffuse through the plasma membrane and enters the blood stream.

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