Fatty+Acid+Synthesis

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Fatty Acid Biosynthesis

By: Joshua P. Blanton, Robert A. Cadena, and Daniel Payne

=Introduction:=

Fatty Acid Synthesis is a process that occurs in the cytosol of the cell. Fatty acid synthesis in mammals occurs on the fatty acyl synthase 1 (FAS I) and in plants it occurs on the fatty acid synthase 2 (FAS II). The enzyme of fatty acid synthesis is the fatty acid synthase for which the coenzyme is NADPH. The process involves creating fatty acids derived biosynthetically from two carbon precursors which are Acetyl-CoA and malonyl-CoA. Acetyl-Coa however is only on the methyl end of the growing fatty acid chain, and all subsequent carbons (14 additional, for a total of 16) come from malonyl-Coa. All carbons come from Acetyl-CoA, but not until they are modified to the actual substrate of the fatty acid chain which is malonyl-CoA. The elongation process repeats until a 16 carbon chain is formed which is palmitate. After that point other enzymes are needed to add double bonds and additional carbons, if they are so required. ( 2 )


 * Acetyl-CoA + 7 malonyl-CoA - + 14 NADPH + 13 H + + H 2 0 ---> palmitate - + 7 HCO - 3 + 8 CoASH + 14 NADP + **

=Fatty Acid Elongation:=

The process of elongation that occurs during fatty acid biosynthesis takes place during four specific reactions. These reactions are very similar to those that occur in the ß -oxidation elongation process. This synthesizing process of fatty acids is used by humans, plants and microorganisms, and is a vital component for life on this planet. This process ends in the yield of a C16 acyl compound which is hydrolized via thioesterase into palmitate and ACP. (1)

Created by Josh Blanton via (Diwan, 2009)

=Pathway:=

The first step of fatty acid biosynthesis is initiated by the enzyme malonyl-CoA-Acetyl-CoA-ACP-transacylase. This enzyme functions by transfering the acetyl portion of Acetyl-CoA to the acyl carrier protein (ACP). Fatty acid biosynthesis occurs on fatty acyl synthase I (FAS I), which is a megasynthase. This megasynthase houses all the individual enzymes utilized in this process as one large protein complex in eukaryotes, hence the term megasynthase.Through a decarboxylation condensation reaction ß -Ketoacyl-ACP synthase (KS) catalyzed the condensation reaction of the acyl group with malonyl-ACP which results in the production of ß -Ketoacyl-ACP intermediate. At this point NADPH and H+ are transferred to Acetoacetyl-ACP by the enzyme ß -Ketoacyl-ACP reductase, which in turn reduces the carbonyl of the terminal acetyl group to an alcohol functional group. Next B-hydroxyacyl-ACP dehydratase is catalyzed through elimination which results in the loss of the OH functional group and in turn produces a carbon carbon double bond between the terminal acteyl moiety and the malonyl moiety. This now yields us with Crotonyl-ACP. The enzyme ß -Enoyl-ACP reductase (ER) hydrogenates the double carbon carbon bond of the Crotonyl-ACP producing Butyryl-ACP. During this reaction NADPH+ is a cofactor that saturates Butyryl-ACP with hydrogen. The concludes the end of the first cycle yielding us with Butyryl-ACP. Now this Butyryl-ACP is lengthened by two carbons each time there is an addition of the Malonyl molecule. These subsequent cycles elongate the chain by two carbons at a time, condensing Butyryl-ACP with one Malonyl-ACP to form a six carbon ß -Ketoacyl-ACP along with CO2. The next step of this cycle is catalyzed by ß -Ketoacyl-ACP reductase (KR), which in turn reduces ß -Ketoacyl-ACP to the B-alcohol and ß -Hydroxyacyl-ACP with NADPH functioning as the coenzyme. Next a ß -Hyrdroxyacyl-ACP is dehydrated to ß -Enoyl-ACP by the ß -Hydroxyacyl-ACP dehydratase (DH). Now ß -Enoyl-ACP is reduced and the carbon chain has grown been elongated by two carbons and is now fully saturated. This semi-final reaction is catalyzed by ß -Enoyl-ACP reductase (ER) and NADPH is used as a coenzyme. A total of six two carbon units are added to the Butyryl-ACP creating a sixteen carbon fatty acid chain. The final reaction is catalyzed by Thioesterase (TE) causing a hydrolysis reaction that yields palmitate and a free ACP. (2)

Garret/Grisham pg. 728

=References:=

1.) //Diwan, J. J. (2009). Fatty Acid Synthasis. Retrieved December 6, 2010, from Molecular Biochemistry II: http://rpi.edu/dept/bcbp/molbiochem/MBWeb// ///mb2/part1/fasynthesis.htm//  2.) //Reginald H. Garrett, C. M. (2010). Lipid Biosynthesis. In C. M. Reginald H. Garrett, Biochemistry (pp. 722-737). Boston: Brooks/Cole.//