Fatty Acid Synthesis - Rensselaer Polytechnic Institute：脂肪酸合成-伦斯勒理工学院.pptVIP

Fatty Acid Synthesis ATP-dependent carboxylation provides energy input. The CO2 is lost later during condensation with the growing fatty acid. The spontaneous decarboxylation drives the condensation reaction. As with other carboxylation reactions, the enzyme prosthetic group is biotin.? ATP-dependent carboxylation of the biotin, carried out at one active site 1 , is followed by transfer of the carboxyl group to acetyl-CoA at a second active site 2 . The overall reaction, which is spontaneous, may be summarized as: HCO3- + ATP + acetyl-CoA ? ADP + Pi + malonyl-CoA Biotin is linked to the enzyme by an amide bond between the terminal carboxyl of the biotin side chain and the e-amino group of a lysine residue. The combined biotin and lysine side chains act as a long flexible arm that allows the biotin ring to translocate between the 2 active sites. Acetyl-CoA Carboxylase, which converts acetyl-CoA to malonyl-CoA, is the committed step of the fatty acid synthesis pathway. The mammalian enzyme is regulated, by phosphorylation allosteric control by local metabolites. AMP functions as an energy sensor and regulator of metabolism. When ATP production does not keep up with needs, a higher portion of a cells adenine nucleotide pool is in the form of AMP. AMP promotes catabolic pathways that lead to synthesis of ATP. AMP inhibits energy-utilizing synthetic pathways. E.g., AMP regulates fatty acid synthesis and catabolism by controlling availability of malonyl-CoA. Fatty acid synthesis is diminished by lack of the substrate malonyl-CoA. As discussed earlier, fatty acid oxidation is stimulated due to decreased inhibition by malonyl-CoA of transfer of fatty acids into mitochondria. result in phosphorylation of Acetyl-CoA Carboxylase via cAMP-Dependent Protein Kinase. With Acetyl-CoA Carboxylase inhibited, acetyl-CoA remains available for synthesis of ketone bodies, the alternative metabolic fuel used when blood glucose is low. The antagonistic effect