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Lipid Synthesis Saturated FA production FA synthase enzyme Role of citrate Unsaturated FA production Regulation of FA synthesis Insulin, glucagon, citrate Triacylglycerols and phospholipids Cholesterol synthesis Transport into body: LDL’s, VLDL’s, HDL’s, etc Regulation Therapeutics to lower cholesterol Leptin Role in FA metabolism Lipid synthesis Fatty acid synthesis: Acetate is a precursor to lipid biosynthesis Uses separate enzymes than in β-oxidation Occurs in cytoplasm Citrate is required as an activator Carried out by Fatty acid synthase enzyme a complex with many subunits Acetyl CoA carboxylase creates malonly CoA contains biotin The rest of the reactions carried out in the Fatty acid synthase complex (reactions on the right) Repeating 8 step process (including carboxylase step) Lipid synthesis This process is repeated until a C16 is made Palmitoyl thioesterase removes the ACP from the fatty acid (C16) 8 AcCoA, 7 ATP, 14 NADPH = 1 palmitic acid (C16) Lipid synthesis Where do we get the NADPH from? Pentose Phosphate pathway or from Malic enzyme in fat cells (mal + NADP+ ? Pyr + CO2 + NADPH) Where does lipid synthesis occur? FA synthesis happens in cytoplasm, (where does β-oxidation occur?) or in chloroplasts of plants Excess AcCoA in mitochondria is converted to Citrate to be transported out of mitochondria Can be shuttled back as pyruvate to pick up more AcCoA NET COST IN ATP Unsaturated FA synthesis Double bonds made after completion in animals We can make double bonds at C4, C5, C6, and C9 Involves cytochrome b5 in a series of oxidation/reduction reactions (using NADPH as the electron donor) Unsaturated FA synthesis Some unsaturated FA we cannot make…. Ex: linoleic acid, 18:2 (?9,12) or Linolenic acid, 18:3 (?9,12,15) We don’t have enzyme to oxidize 12 and 15 position Get these from diet (plants, fish, etc.) Hence it is called an “essential fatty acid” What are “omega fatty acids”?? Linolenic is an omega-3 fatty acid Linoleic is a
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