Figure 21 Mitochondrial b-oxidation of valproic acid (44).
In some cases, acyl-CoA conjugates formed from xenobiotic acids can also enter the physiological pathways of fatty acids catabolism or anabolism. A few examples are known of xenobiotic alkanoic and arylalkanoic acids undergoing two-carbon chain elongation. Other cases involve the opposite, namely two-, four-, or even six-carbon chain shortening by b-oxidation. An example of two-carbon chain shortening is mentioned in Section 5.06.3.6.2 for 4-phenylbutyric acid (58, Figure 20).
In addition, intermediate metabolites of b-oxidation may also be seen, as illustrated by valproic acid (44, Figure 21). Approximately 50 metabolites of this drug have been characterized; they are formed by cytochrome P450-catalyzed hydroxylations, dehydrogenations, b-oxidation, glucuronidation, and other routes of conjugation (see Sections 5.06.3.4.2, 5.06.3.6.2, and 5.06.3.6.3). Figure 21 shows the b-oxidation of valproic acid seen in mitochondrial preparations.110'111 The resulting metabolites have also been found in unconjugated form in the urine of humans or animals dosed with the drug.
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