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LIPID
BIOSYNTHESIS
Archana Soni
archi22ss@gmail.com
Roles of Lipids
◦ Triacylglyerides as fuels
◦ Glycerophospholipids in membrane
◦ Prostaglandins as signal molecules
◦ Cholesterol and derivatives
Fatty Acid Synthesis
◦ Opposite of beta oxidation in the sense that 2-carbon acetate units are
linked to form even-chain, saturated fatty acids
◦ Differs from Fatty acid degradation
◦ In cytoplasm, not matrix
◦ Acyl carrier protein rather than CoA
◦ Enzymes linked in a complex
◦ Utilizes NADPH
◦ Unique pathways (unlike glycolysis/ gluconeogenesis)
Activation of Acetyl Group
◦ Acetyl CoA carboxylase (analogous to pyruvate carboxylase of
gluconeogenesis)
◦ Requires biotin, ATP
◦ Regulation step—shifts fuel away from CAC
Acetyl CoA Carboxylase and
Regulation
◦ Strict control of fatty acid biosynthesis at key step
◦ Local, hormone, and gene regulation
◦ Involved in regulation of beta oxidation
◦ When fuel is high, acetyl CoA is plentiful, and malonyl CoA is produced
◦ Malonyl CoA may decrease appetite
◦ Malonyl CoA inhibits acylcarnitine transferase
◦ No Fatty acids can get into mitochondria for oxidation
◦ See section 16.9 for detail if interested
Transfer to Acyl Carrier Protein
Four Step Elongation
◦ Step 1: Condensation
◦ Loss of CO2 drives reaction to completion
◦ All happens on enzyme complex
◦ Mechanism:
Steps 2-4: Opposite of beta Oxidation
◦ Input of 2 NADPH
Synthesis of Palmiatate
◦ 16-carbon fatty acid produced in major synthesis complex
◦ Elongations possible with other enzymes
◦ Many organisms can make odd-chain Fatty acids
Synthesis of Unsaturated Fats
◦ Nomenclature of unsaturation
◦ Omega-3 and Omega-6 FA are
“essential” in humans
Prostaglandins and COX
Inhibitors
Cholesterol Biosynthesis
◦ Three Stages: Acetyl CoAIsopentyl
diphosphateSqualeneCholesterol
Medical Applications
◦ Statins inhibit HMG-CoA
Synthase
◦ Same enzyme as ketone body
biosynthesis, but cholesterol
made in cytosol
◦ Another strategy is to trap bile
salts in intestine so that
cholesterol is diverted
Medical Applications
◦ Parasites like malaria make
isopentenyl diphosphate through
a different mechanism
◦ A competitive inhibitor can
selectively kill malaria

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Fatty acid notes

  • 2. Roles of Lipids ◦ Triacylglyerides as fuels ◦ Glycerophospholipids in membrane ◦ Prostaglandins as signal molecules ◦ Cholesterol and derivatives
  • 3. Fatty Acid Synthesis ◦ Opposite of beta oxidation in the sense that 2-carbon acetate units are linked to form even-chain, saturated fatty acids ◦ Differs from Fatty acid degradation ◦ In cytoplasm, not matrix ◦ Acyl carrier protein rather than CoA ◦ Enzymes linked in a complex ◦ Utilizes NADPH ◦ Unique pathways (unlike glycolysis/ gluconeogenesis)
  • 4. Activation of Acetyl Group ◦ Acetyl CoA carboxylase (analogous to pyruvate carboxylase of gluconeogenesis) ◦ Requires biotin, ATP ◦ Regulation step—shifts fuel away from CAC
  • 5. Acetyl CoA Carboxylase and Regulation ◦ Strict control of fatty acid biosynthesis at key step ◦ Local, hormone, and gene regulation ◦ Involved in regulation of beta oxidation ◦ When fuel is high, acetyl CoA is plentiful, and malonyl CoA is produced ◦ Malonyl CoA may decrease appetite ◦ Malonyl CoA inhibits acylcarnitine transferase ◦ No Fatty acids can get into mitochondria for oxidation ◦ See section 16.9 for detail if interested
  • 6. Transfer to Acyl Carrier Protein
  • 7. Four Step Elongation ◦ Step 1: Condensation ◦ Loss of CO2 drives reaction to completion ◦ All happens on enzyme complex ◦ Mechanism:
  • 8. Steps 2-4: Opposite of beta Oxidation ◦ Input of 2 NADPH
  • 9. Synthesis of Palmiatate ◦ 16-carbon fatty acid produced in major synthesis complex ◦ Elongations possible with other enzymes ◦ Many organisms can make odd-chain Fatty acids
  • 10. Synthesis of Unsaturated Fats ◦ Nomenclature of unsaturation ◦ Omega-3 and Omega-6 FA are “essential” in humans
  • 12. Cholesterol Biosynthesis ◦ Three Stages: Acetyl CoAIsopentyl diphosphateSqualeneCholesterol
  • 13. Medical Applications ◦ Statins inhibit HMG-CoA Synthase ◦ Same enzyme as ketone body biosynthesis, but cholesterol made in cytosol ◦ Another strategy is to trap bile salts in intestine so that cholesterol is diverted
  • 14. Medical Applications ◦ Parasites like malaria make isopentenyl diphosphate through a different mechanism ◦ A competitive inhibitor can selectively kill malaria