Fatty Acid Synthesis

Fatty Acid Synthesis - Fatty Acid Synthesis Copyright...

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Unformatted text preview: Fatty Acid Synthesis Copyright 1999-2009 by Joyce J. Diwan. All rights reserved. Molecular Biochemistry II ATP-dependent carboxylation provides energy input. The CO 2 is lost later during condensation with the growing fatty acid. The spontaneous decarboxylation drives the condensation reaction. H 3 C C SCoA O CH 2 C SCoA O- OOC acetyl-CoA malonyl-CoA The input to fatty acid synthesis is acetyl-CoA , which is carboxylated to malonyl-CoA . 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 . Acetyl-CoA Carboxylase catalyzes the 2-step reaction by which acetyl-CoA is carboxylated to form malonyl-CoA . ll Enzyme-biotin HCO 3- + ATP ADP + P i Enzyme-biotin-CO 2- O CH 3-C-SCoA acetyl-CoA O- O 2 C-CH 2-C-SCoA malonyl-CoA ll Enzyme-biotin 1 2 The overall reaction, which is spontaneous , may be summarized as: HCO 3- + ATP + acetyl-CoA ADP + P i + malonyl- CoA ll Enzyme-biotin HCO 3- + ATP ADP + P i Enzyme-biotin-CO 2- O CH 3-C-SCoA acetyl-CoA O- O 2 C-CH 2-C-SCoA malonyl-CoA ll Enzyme-biotin 1 2 Biotin is linked to the enzyme by an amide bond between the terminal carboxyl of the biotin side chain and the -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. CH CH H 2 C S CH NH C N O (CH 2 ) 4 C NH (CH 2 ) 4 CH C O NH O C O O- Carboxybiotin lysine residue 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. Conformational changes associated with regulation: In the active conformation, Acetyl-CoA Carboxylase associates to form multimeric filamentous complexes. Transition to the inactive conformation is associated with dissociation to yield the monomeric form of the enzyme (protomer). AMP functions as an energy sensor and regulator of metabolism. When ATP production does not keep up with needs, a higher portion of a cell's 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....
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This note was uploaded on 09/25/2010 for the course BCH 4024 taught by Professor Allison during the Spring '08 term at University of Florida.

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Fatty Acid Synthesis - Fatty Acid Synthesis Copyright...

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