Lipid metabolism denovo synthesis of fatty acids ppt BIOCHEMISTRY vkunder637@gmail.com

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Lipid metabolism denovo synthesis of fatty acids ppt BIOCHEMISTRY vkunder637@gmail.com

  1. 1. Dr. Vijay Marakala, MBBS, MD. Assistant professor BIOCHEMISTRY SIMS & RC
  2. 2. De Novo synthesis of fatty acids • Saturated fatty acids are synthesized from acetyl CoA derived from glucose • Occur in cytoplasm Elongation of fatty acids • Acetyl fragments are added to the existing fatty acids • Occur in both cytoplasm and mitochondria Desaturation of fatty acids • Double bonds are introduced into the fatty acids • Occur in microsomes
  3. 3. Acetyl CoA Palmitic acid Stearic acid Oleic acid C-2 C-16 fatty acid C-18 fatty acid C-18 fatty acid, Unsaturated ∆9 De novo synthesis Elongation Desaturation
  4. 4. Definition Differences b/w synthesis and oxidation Phases of FA synthesis Reactions [Pathway] Regulation
  5. 5. Definition De novo synthesis of fatty acid is the synthesis of saturated fatty acids from acetyl CoA that is primarily derived from glucose
  6. 6. » Occurs mainly in and LACTATING MAMMARY GLAND synthesis means new synthesis from amphibolic compounds » In FA biosynthesis used as
  7. 7. » carbohydrate intake  - acetyl CoA  - fatty acids synthesis » Occurred in cytosol » Need - acetyl CoA - NADPH ( from HMP shunt )
  8. 8. SYNTHESIS DEGRADATION Intermediates Linked to SH in Proteins (Acyl Carrier Proteins) Linked to CoASH Site Cytosol Mitochondria Enzymes Components of single Peptide Separate Polypeptides Redox Coenzymes NADP+ / NADPH NAD+ / NADH
  9. 9. Transport of substrates into cytosol Carboxylation of acetyl-CoA to malonyl-CoA Utilization of substrate to form palmitate By enzyme complex fatty acid synthase Elongation and desaturation of palmitate To generate different fatty acids
  10. 10. Phase I Transport of substrates into cytosol Carboxylation of acetyl-CoA to malonyl-CoA
  11. 11. Citrate Citrate Oxaloacetate Malate PyruvatePyruvate Oxaloacetate
  12. 12. Phase I Transport of substrates into cytosol Carboxylation of acetyl-CoA to malonyl-CoA
  13. 13. Phase II Utilization of substrate to form palmitate By enzyme FATTY ACID SYNTHASE COMPLEX
  14. 14. » Is a polypeptide containing seven enzyme activities and acyl carrier protein (ACP) segment
  15. 15. Condensation
  16. 16. Reduction
  17. 17. Dehydration
  18. 18. 5 Reduction
  19. 19. PALMITATE THIOESTERASE H2O
  20. 20. Acetyl CoA Malonyl CoA Acetyl S-enzyme Acetyl malonyl S-enzyme 3-ketoacyl S-enzyme 3-Hydroxyacyl S-enzyme 2,3-Unsaturated acyl S-enzyme Acyl S-enzyme Fattyacidsynthasemultienzymecomplex Acetyl CoA Acetyl transacylase Malonyl transacylase 3-ketoacyl synthase 3-ketoacyl reductase Hydratase Enoyl reductase CoASH Malonyl CoA CoASH CO2 NADPH+H+ NADPH H2O NADPH+H+ NADPH Acetyl CoA carboxylase CO2 ATP ADP + Pi Biotin
  21. 21. Palmitoyl S-enzyme Palmitic acid Fattyacidsynthasemultienzymecomplex Thioesterase Acyl S-enzyme 4 Carbon 16 Carbon After cycling through steps - seven times2 5 H2O
  22. 22. Enzymes Metabolites End products Hormones Diet Fatty acid synthesis is regulated by
  23. 23. Enzymes • Acetyl CoA carboxylase Metabolites • Citrate End products • Palmitoyl CoA Hormones • Insulin • Glucagon Diet • High carbohydrate diet
  24. 24. Glucagon
  25. 25. High carbohydrate diet Acetyl-CoA carboxylase Insulin High fat diet Starvation Diabetes mellitus + + + - --
  26. 26. Elongation of fatty acids • Acetyl fragments (from malonyl CoA) are added to the existing fatty acids • Occur in both ER and mitochondria

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