Hydroxy lation fatty acids

RH above can represent a very wide variety of xenobi-otics, including drugs, carcinogens, pesticides, petroleum products, and pollutants (such as a mixture of PCBs). In addition, endogenous compounds, such as certain steroids, eicosanoids, fatty acids, and retinoids, are also substrates. The substrates are generally lipophilic and are rendered more hydrophilic by hydroxy-lation. 

The co-hydroxylation of fatty acids, which involves the addition of a hydroxyl group at or near the co-terminal carbon, was first shown to be catalyzed by the liver microsomal enzyme system in the 1960s [38], In particular, the CO pigment of CYP was recognized as a constituent of the microsomal mixed function oxidase system that contributes to the co-hydroxylation of steroids [39], Substrates that are susceptible to co-hydroxylation include laurate and AA [38], Early reports showed that CYP enzymes catalyze the CO (C-20) and co-1 (C-19) hydroxy lation of AA [40], In 1990, Faick et al. demonstrated that CYP enzymes also hydroxy late the C-16 (co-4), C-17 (co-3), and C-18 (co-2) carbons of A A [41], Thus, in the presence of nicotinamide adenine dinucleotide phosphate (NADPH) and molecular oxygen, CYPs mediate the hydroxylation of AA to generate a variety of co-terminal HETEs including 16-, 17-, 18-, 19-, and 20-HETR (Fig. 13.2). 

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