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Transcript
11/29/16 The pathway from “activated acetic acid” to fatty acids and terpenes Feodor Lynen (The fatty acid cycle) 1 11/29/16 Feodor Lynen, Nobel Prize 1964, Fatty Acid Metabolism Triglycerides are also stored in muscle 2 11/29/16 Lipases hydrolyze triglycerides 3 11/29/16 Fatty acid degradation – standard sequence Acyl CoA Synthase Adenylation of FA drives formation of thioester Essentially 2 ATPs hydrolyzed Amino acids activated in the same way for attachment to tRNA Mitochondrial outer membrane 4 11/29/16 Fatty acyl spiral Acyl CoA dehydrogenase L-3-hydroxyacyl CoA reductase Enoyl CoA hydratase β-keto thiolase 5 11/29/16 6 11/29/16 Odd numbered FAs yield: Ketone bodies are formed from acetyl CoA when fat metabolism predominates- Balance of carbohydrate and fatty acid metabolism: AcetylCoA can only enter CA cycle by reacting with oxaloacetate. Need pyruvate from glucose to keep oxaloacetate at sufficient levels. Formation of ketone bodies. Discovered HMG-CoA cycle-intermediates in synthesis of terpenes and cholesterol (like citric acid cycle). See Ch 26, Fig. 26.8 7 11/29/16 8 11/29/16 Fatty Acid Synthesis-Intermediates Attached to acyl carrier protein Fatty acid synthesis Formation of Malonyl CoA by Acetyl CoA carboxylase Biotin-enzyme +ATP+HCO3CO2-biotin+acetyl CoA CO2-biotin-enzyme plus ADP +Pi malonyl CoA + biotin enzyme Committed step in FA biosynthesis Acetyl CoA Carboxylase 9 11/29/16 10 11/29/16 Pyruvate dehydrogenase is irreversible and so is Pyruvate kinase Need to make phosphoenolpyruvate from oxaloacetate to reverse glycolysis for gluconeogenesis Variations on a theme: ketide synthesis (Also peptides) 11 11/29/16 12 11/29/16 13 11/29/16 14 11/29/16 15 11/29/16 16 11/29/16 17 11/29/16 18