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The document summarizes de novo fatty acid synthesis. It occurs in the liver, kidney, adipose tissue, and lactating mammary gland. Enzymes are located in the cytosol. Acetyl CoA from the mitochondria is the starting material and is converted to malonyl CoA by acetyl CoA carboxylase in an ATP-dependent reaction. Fatty acid synthase complex then catalyzes sequential reactions to produce palmitate through seven cycles. Production is regulated by enzymes, metabolites, hormones, and diet.

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Dr. Mukhtar Jama Nour, MBBS , MD
皃 De novo synthesis of fatty acids occurs in liver, kidney, adipose tissue & lactating mammary gland. 皃 Enzymes are located in cytosomal fraction of the cell. 皃 It is called as extramitochondrial or cytoplasmic fatty acid synthase system.
皃 Major fatty acid synthesized de novo is palmitic acid (16C saturated fatty acid). 皃 It occurs in liver, adipose tissue, kidney, brain & lactating mammary glands. 皃 Acetyl CoA is the source of carbon atoms.
皃 Every molecule of acetyl CoA delivered to cytoplasm, one molecule of NADPH is formed. 皃 ATPsupplies energy.
皃 Production of acetyl CoA & NADPH 皃 Conversion of acetyl CoA to malonyl CoA 皃 Reactions of fatty acid synthase complex.
皃 Acetyl CoA is the starting material for de novo synthesis of fatty acids. 皃 Acetyl CoA is produced in the mitochondria by the oxidation of pyruvate, fatty acids, degradation of carbon skeleton of certain amino acids & from ketone bodies. 皃 Mitochondria are not permeable to acetyl CoA.
皃 An alternate or a bypass arrangement is made for the transfer of acetyl CoA to cytosol. 皃 Acetyl CoA condenses with oxaloacetate in mitochondria to form citrate. 皃 Citrate is freely transported to cytosol by tricarboxylic acid transporter. In cytosol it is cleaved by ATP citrate lyase to liberate acetyl CoA & oxaloacetate.
Glucose Oxaloacetate Citrate Mitochondrial matrix Pyruvate Acetyl CoA Citrate Oxaloacetate Amino acids FA Pyruvate carboxylase PDH Complex Citrate synthase ADP+Pi Acetyl CoA ATP CoASH Citrate lyase MDH NADH + H+ Pyruvate NADPH + H+ HMP Shunt CO2 NADP+ Malate NAD+ Fatty acid Cytosol Transfer of acetyl CoA from mitochondria to cytosol Malic enzyme
皃 Acetyl CoA is carboxylated to malonyl CoA by the enzyme acetyl CoA carboxylase. 皃 This is an ATP-dependent reaction & requires biotin for CO2fixation.
O CH3 C SCoA Acety CoA ADP + Pi O -OOC CH2 C SCoA Malonyl CoA Acetyl CoA carboxylase CO2, ATP Biotin
皃 At the end of 7cycles, the fatty acid synthesis is complete & a 16-carbon fully saturated fatty acid-namely palmitate-bound to ACPis produced. 皃 The enzyme palmitoyl thioesterase separates palmitate from fatty acid synthase. 皃 This completes the synthesis of palmitate
皃 The FAScomplex offers great efficiency that is free from interference of other cellular reactions for the synthesis of fatty acids. 皃 There is a good coordination in the synthesis of all enzymes of the FAS complex.
皃 Fatty acid production is controlled by enzymes, metabolites, end products, hormones and dietary manipulations. 皃 Acetyl CoA carboxylase: 皃 This enzyme controls a committed step in fatty acid synthesis.
皃 Glucagon, epinephrine & norepinephrine inactivate the enzyme by cAMP dependent phosphorylation.
皃 Insulin, dephosphorylates & activates the enzyme. 皃 Insulin promotes fatty acid synthesis while glucagon inhibits. 皃 Insulin stimulates tissue uptake of glucose & conversion of pyruvate to acetyl CoA.
皃 Consumption of high carbohydrate or fat-free diet increases the synthesis of acetyl CoA carboxylase & fatty acid synthase, which promote fatty acid formation. 皃 Fasting or high fat diet decreases fatty acid production by reducing the synthesis of acetyl CoA carboxylase & FAS.
皃 The reducing equivalents for fatty acid synthesis are provided by NADPH which come either from citrate (acetyl CoA) .
fatty acid (1).pptx

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fatty acid (1).pptx

  • 2. 皃 De novo synthesis of fatty acids occurs in liver, kidney, adipose tissue & lactating mammary gland. 皃 Enzymes are located in cytosomal fraction of the cell. 皃 It is called as extramitochondrial or cytoplasmic fatty acid synthase system.
  • 3. 皃 Major fatty acid synthesized de novo is palmitic acid (16C saturated fatty acid). 皃 It occurs in liver, adipose tissue, kidney, brain & lactating mammary glands. 皃 Acetyl CoA is the source of carbon atoms.
  • 4. 皃 Every molecule of acetyl CoA delivered to cytoplasm, one molecule of NADPH is formed. 皃 ATPsupplies energy.
  • 5. 皃 Production of acetyl CoA & NADPH 皃 Conversion of acetyl CoA to malonyl CoA 皃 Reactions of fatty acid synthase complex.
  • 6. 皃 Acetyl CoA is the starting material for de novo synthesis of fatty acids. 皃 Acetyl CoA is produced in the mitochondria by the oxidation of pyruvate, fatty acids, degradation of carbon skeleton of certain amino acids & from ketone bodies. 皃 Mitochondria are not permeable to acetyl CoA.
  • 7. 皃 An alternate or a bypass arrangement is made for the transfer of acetyl CoA to cytosol. 皃 Acetyl CoA condenses with oxaloacetate in mitochondria to form citrate. 皃 Citrate is freely transported to cytosol by tricarboxylic acid transporter. In cytosol it is cleaved by ATP citrate lyase to liberate acetyl CoA & oxaloacetate.
  • 8. Glucose Oxaloacetate Citrate Mitochondrial matrix Pyruvate Acetyl CoA Citrate Oxaloacetate Amino acids FA Pyruvate carboxylase PDH Complex Citrate synthase ADP+Pi Acetyl CoA ATP CoASH Citrate lyase MDH NADH + H+ Pyruvate NADPH + H+ HMP Shunt CO2 NADP+ Malate NAD+ Fatty acid Cytosol Transfer of acetyl CoA from mitochondria to cytosol Malic enzyme
  • 9. 皃 Acetyl CoA is carboxylated to malonyl CoA by the enzyme acetyl CoA carboxylase. 皃 This is an ATP-dependent reaction & requires biotin for CO2fixation.
  • 10. O CH3 C SCoA Acety CoA ADP + Pi O -OOC CH2 C SCoA Malonyl CoA Acetyl CoA carboxylase CO2, ATP Biotin
  • 11. 皃 At the end of 7cycles, the fatty acid synthesis is complete & a 16-carbon fully saturated fatty acid-namely palmitate-bound to ACPis produced. 皃 The enzyme palmitoyl thioesterase separates palmitate from fatty acid synthase. 皃 This completes the synthesis of palmitate
  • 12. 皃 The FAScomplex offers great efficiency that is free from interference of other cellular reactions for the synthesis of fatty acids. 皃 There is a good coordination in the synthesis of all enzymes of the FAS complex.
  • 13. 皃 Fatty acid production is controlled by enzymes, metabolites, end products, hormones and dietary manipulations. 皃 Acetyl CoA carboxylase: 皃 This enzyme controls a committed step in fatty acid synthesis.
  • 14. 皃 Glucagon, epinephrine & norepinephrine inactivate the enzyme by cAMP dependent phosphorylation.
  • 15. 皃 Insulin, dephosphorylates & activates the enzyme. 皃 Insulin promotes fatty acid synthesis while glucagon inhibits. 皃 Insulin stimulates tissue uptake of glucose & conversion of pyruvate to acetyl CoA.
  • 16. 皃 Consumption of high carbohydrate or fat-free diet increases the synthesis of acetyl CoA carboxylase & fatty acid synthase, which promote fatty acid formation. 皃 Fasting or high fat diet decreases fatty acid production by reducing the synthesis of acetyl CoA carboxylase & FAS.
  • 17. 皃 The reducing equivalents for fatty acid synthesis are provided by NADPH which come either from citrate (acetyl CoA) .