PT  - JOURNAL ARTICLE
AU  - P W Albro
AU  - K Chae
AU  - R Philpot
AU  - J T Corbett
AU  - J Schroeder
AU  - S Jordan
TI  - In vitro metabolism of mono-2-ethylhexyl phthalate by microsomal enzymes. Similarity to omega- and (omega-1) oxidation of fatty acids.
DP  - 1984 Nov 01
TA  - Drug Metabolism and Disposition
PG  - 742--748
VI  - 12
IP  - 6
4099  - http://dmd.aspetjournals.org/content/12/6/742.short
4100  - http://dmd.aspetjournals.org/content/12/6/742.full
SO  - Drug Metab Dispos1984 Nov 01; 12
AB  - Mono-2-ethylhexyl pthalate (MEHP) is oxidized to omega-, omega-1-, and omega-2-hydroxylation products as well as (very slightly) to a dicarboxylic acid by washed microsomes from rat liver and kidney, and rabbit but not rat lung. The reactions involve molecular oxygen, are strongly inhibited by carbon monoxide and oxidized cytochrome c, and NADPH is preferred over NADH. Piperonyl butoxide inhibits hydroxylation of MEHP, but clofibrate does not. The differential effects of inducers (phenobarbital and clofibrate) and inhibitors (sodium laurate, n-decane, metyrapone) on terminal and subterminal hydroxylation as well as differences in apparent Km for the two suggest that rat liver contains at least two different MEHP hydroxylases. Comparisons of tissue distribution, susceptibility to inhibitors, and induction properties suggest that the hydroxylation of MEHP is more likely to be mediated by the P-450 isozymes associated with omega- and (omega-1)-hydroxylation of fatty acids than with those that utilize hydrocarbons as substrates.