10-9-2+Lipid+Metabolism.ppt

The Differences Between fatty acid biosynthesis and breakdown Intermediates in synthesis are linked to -SH groups of acyl carrier proteins (as compared to -SH groups of CoA Synthesis in cytosol; breakdown in mitochondria Enzymes of synthesis are one polypeptide Biosynthesis uses NADPH/NADP+; breakdown uses NADH/NAD+ and FAD/FADH2 Features Cellular location-cytosol Primers-- acetyl-CoA Activated 2-C units - malonyl-CoA Decarboxylation of malonyl-CoA and reducing power of NADPH drive chain growth Chain grows to 16-carbons Other enzymes add double bonds and more Cs Challenge: Ac-CoA in Cytosol What are the sources? Amino acid degradation produces cytosolic acetyl-CoA FA oxidation produces mitochondrial acetyl-CoA Glycolysis yields cytosolic pyruvate which is converted to acetyl-CoA in mitochondria Citrate-malate-pyruvate shuttle provides cytosolic acetate units and reducing equivalents for fatty acid synthesis The citrate-malate-pyruvate shuttle 柠檬酸－丙酮酸循环 （1）乙酰CoA+OAA→Cit→胞浆 FA合成的第一个关键反应 （2）丙二酸单酰CoA的形成（乙酰CoA羧化酶催化） FA合成的第二个关键反应 ，是FA合成的限速反应。 Regulation of Fatty Acid Synthesis （3）FA的合成需要NADPH，NADPH主要来自糖代 谢的戊糖磷酸途径 Acetyl-CoA Carboxylase ACC forms long, active filamentous polymers from inactive protomers As a committed step, ACC is carefully regulated Palmitoyl-CoA (product) favors monomers Citrate favors the active polymeric form Phosphorylation modulates citrate activation and palmitoyl-CoA inhibition Fatty Acid Synthesis in Animals Fatty Acid Synthase - a multienzyme complex Dimer of 250 kD multifunctional polypeptides the roles of active site serines on AT MT Steps 3-6 repeat to elongate the chain Now what…? Elongation Desaturation Fatty Acid Modification Elongation, beyond the 16-C length of palmitate, occurs in mitochondria. Endoplasmic reticulum enzymes also yield longer fatty acids. Fatty acid elongation within mitochondria occurs via b-oxidation running in reverse, except that NADPH serves as electron donor fo