BIOSYNTHESIS OF SATURATED FATTY ACIDS
The biosynthesis of saturated fatty acids from the their ultimate precursor acetyl - CoA occurs in all organism but is particularly prominent in the liver, adipose tissues, and mammary glands of higher animals. It is brought about by a process that differs significantly from the opposed process of fatty acid oxidation. In the first place total biosynthesis of fatty acids occurs in the cytosol, whereas fatty oxidation occurs in the mitochondria. Second, the presence of citrate for maximal rates of synthesis of fatty acids, whereas it is not required in fatty acid oxidation. Perhaps the most unexpected difference is that CO2 is essential for fatty acid synthesis in cell extracts, although isotopic CO2 is not itself incorporated into the newly synthesized fatty acids. These and many other observations have revealed that fatty acid synthesis from acetyl-CoA takes place with an entirely different set of enzymes from those employed in fatty acid oxidation. In the overall reaction of fatty acid synthesis, which is catalyzed by a cluster of seven proteins in the cytosol, the fatty - acid synthetase complex, acetyl-CoA derived from carbohydrate or amino acid sources is the ultimate precursor of all the carbon atoms of the fatty acid chain. However, of the eight acetyl units required for biosynthesis of palmitic acid, only one is provided by acetyl- CoA; the other seven arrive in the form of malonyl-CoA; formed from acetyl-CoA and Hco3-in a carboxylation reaction. One acetyl residue and seven malonyl residues undergo successive condensation steps, with release of seven molecules of CO2, to for palmitic acid; the reducing power is furnished by NADPH;.
Acetyl-CoA + 7 malonyl-CoA + 14NADPH + 14H+� CH3 (CH2)14 COOH+7CO2+ 8CoA + 14NADP+ + 6H3O
The single molecule of acetyl-CoA required in the process serves as a primer, or starter; the two carbon atoms of its acetyl group become the two terminal carbon atoms (15 and 16) of the palmitic acid formed. Chain growth during fatty acid synthesis thus at the carboxyl group of acetyl-CoA and proceeds by successive addition of acetyl residues at the carboxyl end of the growing chain. Each successive acetyl residues at the is derived from two of the three carbon atoms of a malonic acid residue entering the system in the form of malony_CoA; the third carbon atom of malonic acid, i.e. that of the unesterified carboxyl group, is lost as CO2. The final product is a molecule of palmitic acid. A distinctive feature of the mechanism of fatty acid biosynthesis is that the acyl intermediates in the process of chain lengthening are thio esters, not of CoA, as in fatty acid oxidation, but of a low-molecular-weight conjugated protein called acyl protein (ACP). This protein can form a complex or complexes with the six other enzyme proteins required for the complete synthesis of palmitic acid.