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Abstract

Human liver lauric acid hydroxylase activities.

P J Castle, J L Merdink, J R Okita, S A Wrighton and R T Okita
Drug Metabolism and Disposition October 1995, 23 (10) 1037-1043;
P J Castle
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J L Merdink
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J R Okita
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S A Wrighton
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R T Okita
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Abstract

Nine male and five female human liver microsomal sample were examined for laurate 11- and 12-hydroxylase activities. The mean specific activities for the 11- and 12-hydroxylation reactions were 0.78 +/- 0.33 and 1.07 +/- 0.12 nmol/min/mg protein, respectively. Antibody inhibition experiments, using a polyclonal antibody to a cytochrome P450 (P450) isolated from diethylhexyl phthalate-treated rats, which recognizes forms P4504A1, P4504A2, and P4504A3 of the rate, inhibited the 12-hydroxylase activity by 65%, but did not affect 11-hydroxylase activity. Western-blot analyses of the 14 human liver microsomal samples identified one major protein band at 52 kDa that comigrated with human form 4A11. A correlation coefficient of only 0.19 was calculated when comparing laurate 12-hydroxylase activities and the densitometric values of the immunochemically reactive protein bands in the human liver microsomal samples, which strongly suggests that additional P450 forms also support the 12-hydroxylation of lauric acid. Laurate 11-hydroxylase activity was inhibited by diethyldithiocarbamate, an inhibitor of P4502E1-mediated reactions, and by chlorzoxazone, a P4502E1 substrate. A comparison of laurate 11-hydroxylase activities with densitometric values of the P4502E1 protein bands indicated a strong correlation existed (0.82). An analysis of microsomal samples containing expressed human forms P4501A2, P4502A6, P4502C8, P4502C9, P4502D6, P4502E1, and P4503A4 showed that only form P4502E1 supported the 11-hydroxylation reaction.

 

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Drug Metabolism and Disposition
Vol. 23, Issue 10
1 Oct 1995
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Abstract

Human liver lauric acid hydroxylase activities.

P J Castle, J L Merdink, J R Okita, S A Wrighton and R T Okita
Drug Metabolism and Disposition October 1, 1995, 23 (10) 1037-1043;

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Abstract

Human liver lauric acid hydroxylase activities.

P J Castle, J L Merdink, J R Okita, S A Wrighton and R T Okita
Drug Metabolism and Disposition October 1, 1995, 23 (10) 1037-1043;
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