Fatty Acid Biosynthesis - Texas Aamp;M University：脂肪酸的生物合成-德克萨斯amp；M大学.pptVIP

LIPID BIOSYNTHESIS Fatty acid biosynthesis-basic fundamentals Fatty acid biosynthesis-elongation and desaturation Triacylglycerols Phospholipids Cholesterol Cholesterol metabolism Fatty Acid Biosynthesis Cytosol Requires NADPH Acyl carrier protein D-isomer CO2 activation Keto ? saturated Mitochondria NADH, FADH2 CoA L-isomer No CO2 Saturated ? keto Acetyl-CoA CarboxylaseThe rate-controlling enzyme of FA synthesis In Bacteria -3 proteins (1) Carrier protein with Biotin (2) Biotin carboxylase (3) Transcarboxylase In Eukaryotes - 1 protein (1) Single protein, 2 identical polypeptide chains (2) Each chain Mwt = 230,000 (230 kDa) (3) Dimer inactive (4) Activated by citrate which forms filamentous form of protein that can be seen in the electron microscope Overall Reactions Post-Synthesis Modifications C16 satd fatty acid (Palmitate) is the product Elongation Unsaturation Incorporation into triacylglycerols Incorporation into acylglycerol phosphates * Beta Oxidation Synthesis Rule: Fatty acid biosynthesis is a stepwise assembly of acetyl-CoA units (mostly as malonyl-CoA) ending with palmitate (C16 saturated) Activation Elongation Termination 3 Phases CH3C~SCoA O ACTIVATION -OOC-CH2C~SCoA O HCO3- Carboxybiocytin Biotin active carbon Acetyl-CoA carboxylase CO2 Biocytin Cofactor ATP ADP + Pi Yeast Fatty Acid Synthase Complex 2,500 kDa Multienzyme Complex 6 molecules of 2 peptide chains called A and B (?6?6) A: (185,000) Acyl Carrier protein ?-ketoacyl-ACP synthase (condensing enzyme) ?-ketoacyl-ACP reductase B: (175,000) ?-hydroxy-ACP dehydrase enoyl-ACP reductase palmitoyl thioesterase Fatty Acid Synthase Complex Acyl carrier protein 10 kDa Cysteamine Phosphopantetheine HS-CH2-CH2-N-C-CH2-CH2-N-C-C-C-CH2-O-P-O-P-O-CH2 O O O O H H H HO CH3 H O O O Adenine O-P-O O OH OH H Coenzyme A Acyl Carrier Protein HS-CH2-CH2-N-C-CH2-CH2-N-C-C-C-CH2-O-P-O-CH2-Ser- O O O O H H H HO CH3 H ACP Overall Reaction CH3