Steroid hormone hydroxylase specificities of eleven cDNA-expressed human cytochrome P450s.

  title={Steroid hormone hydroxylase specificities of eleven cDNA-expressed human cytochrome P450s.},
  author={David J. Waxman and D P Lapenson and Toshifumi Aoyama and H. V. Gelboin and Frank J. Gonzalez and Kenneth Ray Korzekwa},
  journal={Archives of biochemistry and biophysics},
  volume={290 1},

Allelic variants of human cytochrome P450 1A1 (CYP1A1): effect of T461N and I462V substitutions on steroid hydroxylase specificity.

Results indicate that all three naturally occurring allelic variants of human CYP1A1 hydroxylate steroid hormones with varying efficiencies in a stereo- and regioselective manner, whereby the CYP 1A1 T461N variant exhibited the lowest catalytic efficiency.

Cytochrome P450 3A9 catalyzes the metabolism of progesterone and other steroid hormones

As a major isoform of CYP3A expressed in rat brain, the activities of P450 3A9 toward two major neurosteroids, progesterone and DHEA suggested a possible role for P4503A9 in the metabolism of neurosteroid metabolism.

16 α-Hydroxylation of estrone by human cytochrome P 4503 A 4 / 5

The cytochrome P450 (P450) enzymes that catalyse metabolism of the estrogen, estrone (E1), to the putative carcinogen 16α-hydroxy E1 (16α-OHE1) in humans were determined. The potential of the most

16Alpha-hydroxylation of estrone by human cytochrome P4503A4/5.

The cytochrome P450 (P450) enzymes that catalyse metabolism of the estrogen, estrone (E1), to the putative carcinogen 16alpha-hydroxy E1 (16alpha-OHE1) in humans were determined. The potential of the

Progesterone and testosterone hydroxylation by cytochromes P450 2C19, 2C9, and 3A4 in human liver microsomes.

The results suggest that CYP2C19 plays important roles in the oxidation of progesterone and testosterone in human liver microsomes, although the physiological significance of these metabolic pathways remains unclear.

Differential activation of cyclophosphamide and ifosphamide by cytochromes P-450 2B and 3A in human liver microsomes.

It is established that liver microsomal CYP2B and CYP3A preferentially catalyze cyclophosphamide and ifosphamide 4-hydroxylation, respectively, suggesting that liver P-450-inducing agents targeted at these enzymes might be used in cancer patients to enhance drug activation and therapeutic efficacy.

Separate and interactive regulation of cytochrome P450 3A4 by triiodothyronine, dexamethasone, and growth hormone in cultured hepatocytes.

It is concluded that iodothyronines, glucocorticoids, and GH act directly on human hepatocytes to regulate the expression of CYP3A4, and these effects appear to be exerted at a pretranslational level.

Inhibition and activation of the human liver microsomal and human cytochrome P450 3A4 metabolism of testosterone by deployment-related chemicals.

Kinetic analysis indicated that chlorpyrifos was one of the most potent inhibitors of major TST metabolites followed by fonofos and phorate, and inhibited major T ST metabolites noncompetitively and irreversibly.



Estradiol metabolism by complementary deoxyribonucleic acid-expressed human cytochrome P450s.

Results suggest that 2-Hydroxy- and/or 4-hydroxycatechol estrogens are further metabolized to other yet uncharacterized metabolites by P450s IIIA3 and IIIA4, and that these enzymes constitute the major forms catalyzing estradiol oxidation in human liver.

Participation of two structurally related enzymes in rat hepatic microsomal androstenedione 7 alpha-hydroxylation.

It is established that P- 450 RLM2 and P-450 3 can both contribute significantly to microsomal androstenedione 7 alpha-hydroxylation, thus demonstrating that the 7alpha-hydrogenation of this androgen does not serve as a specific catalytic monitor for microsome P-451 3.

The CYP2A3 gene product catalyzes coumarin 7-hydroxylation in human liver microsomes.

Analysis of IIA proteins in human liver microsomes, using antibody against rat IIA2, revealed two proteins of 49 and 50 kDa, which appeared to correlate with human microsomal coumarin 7-hydroxylase activity, and a more striking correlation was found between IIA mRNA and enzyme activity.

Regioselective progesterone hydroxylation catalyzed by eleven rat hepatic cytochrome P-450 isozymes.

Quantitative high-pressure liquid chromatographic assays were developed that separate progesterone and 17 authentic monohydroxylated derivatives and indicated that P-450k or an immunochemically related isozyme contributed greater than 80% of the 21-hydroxylase activity observed in microsomes from phenobarbital-induced rats.

Alteration of mouse cytochrome P450coh substrate specificity by mutation of a single amino-acid residue

It is reported that the activities of both cytochromes depend critically on the identities of the amino acids at positions 117, 209 and 365 and, moreover, that a single mutation in which Phe 209 is substituted by Leu is sufficient to convert the specificity of P450coh from coumarin to steroid hydroxylation.

Constitutive testosterone 6 beta-hydroxylase in rat liver.

There was a good correlation (r = 0.925) between the P450 PB-1 level and testosterone 6 beta-hydroxylase activity in rat liver microsomes, and showed that P450PB-1 is a constitutive male-specific form in rat Liver.

Androgen hydroxylation catalysed by a cell line (SD1) that stably expresses rat hepatic cytochrome P-450 PB-4 (IIB1).

These studies establish that a single P-450 gene product (IIB1) can account for the hydroxylation of androgen substrates at multiple sites, and suggest that SD1 cells can be used to assess the catalytic specificity of P- 450 PB-4 with other substrates as well.