Expressed CYP4A4 metabolism of prostaglandin E(1) and arachidonic acid.

  title={Expressed CYP4A4 metabolism of prostaglandin E(1) and arachidonic acid.},
  author={A. Aitken and L. Roman and P. A. Loughran and M. de la Garza and B. Masters},
  journal={Archives of biochemistry and biophysics},
  volume={393 2},
Cytochrome P4504A4 (CYP4A4) is a hormonally induced pulmonary cytochrome P450 which metabolizes prostaglandins and arachidonic acid (AA) to their omega-hydroxylated products. Although the physiological function of this enzyme is unknown, prostaglandins play an important role in the regulation of reproductive, vascular, intestinal, and inflammatory systems and 20-hydroxyeicosatetraenoic acid, the omega-hydroxylated product of arachidonate, is a potent vasoconstrictor. Therefore, it is important… Expand
The substrate selectivity and expression of arachidonic acid omega-hydroxylases, regulation of these enzymes during disease, and the application of enzyme inhibitors to study 20-HETE function are discussed. Expand
Prostaglandin and leukotriene ω-hydroxylases
Omega and subterminal hydroxylations of prostaglandins, leukotriene B 4, and some related eicosanoids are catalyzed by the cytochrome P450 (CYP) enzymes belonging to the CYP4A and CYP3F subfamilies, and three additional human, four mouse, and one fish members of the CYF4F subfamily have been identified. Expand
Kinetic Analysis of Lauric Acid Hydroxylation by Human Cytochrome P450 4A11
Results indicate that both the transfer of an electron to the ferrous·O2 complex and C–H bond-breaking limit the rate of P450 4A11 ω-oxidation. Expand
Expression of CYP4F8 (prostaglandin H 19-hydroxylase) in human epithelia and prominent induction in epidermis of psoriatic lesions.
It is concluded that CYP4F8 is present in epithelial linings of the gut and urinary tract and up regulated in epidermis of psoriatic lesions of psoriasis. Expand
Endogenous Functions of the Aryl Hydrocarbon Receptor (AHR): Intersection of Cytochrome P450 1 (CYP1)-metabolized Eicosanoids and AHR Biology*
It is proposed that many endogenous and exogenous cellular stimuli lead to (i) AHR-dependent CYP1-dependent eicosanoid synthesis and degradation and (ii) A HR-dependent cytochrome P450-independent (eicOSanoid-dependent and -independent) responses. Expand
Cytochromes P450—A Family of Proteins and Scientists–Understanding their Relationships
The unifying thread of this review involves NADPH-cytochrome P450 reductase (CYPOR), the microsomal enzyme responsible for transferring electrons to cytochromes P450, as well as several otherExpand
Diminished FAD Binding in the Y459H and V492E Antley-Bixler Syndrome Mutants of Human Cytochrome P450 Reductase*
Numerous mutations/polymorphisms of the POR gene, encoding NADPH:cytochrome P450 oxidoreductase (CYPOR), have been described in patients with Antley-Bixler syndrome (ABS), presenting withExpand
Cytochrome P450 expression and activities in rat, rabbit and bovine tongue.
It is suggested that although CYP2E1 is expressed in the tongue, it is rapidly degraded in this organ, and the nitrophenol hydroxylation and caffeine hydroxilation the authors observe is the result of activity of CYP1A1. Expand
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Xenobiotic metabolism in the tongue has received little attention in the literature. In the present study, we report a comparative analysis of constitutive cytochrome P450 (CYP) expression andExpand


ω- and (ω-1)-hydroxylation of eicosanoids and fatty acids by high-performance liquid chromatography
Publisher Summary This chapter discusses the ω and (ω-1)-hydroxylation of eicosanoids and fatty acids by high-performance liquid chromatography (HPLC). Cytochromes P450 of the IVA family catalyze theExpand
The kinetic and spectral characterization of the E. coli-expressed mammalian CYP4A7: cytochrome b5 effects vary with substrate.
Saturation kinetics studies performed with heme-depleted cytochrome b5 yielded turnover numbers of 118 and 74 min(-1) and Km values of 74 and 25 microM with laurate and myristate, respectively, indicating that cyto chrome b5 is not involved in electron transfer but rather plays a conformational role. Expand
Expression of rabbit cytochromes P4504A which catalyze the omega-hydroxylation of arachidonic acid, fatty acids, and prostaglandins.
The results indicate that the enzyme whose mRNA is most highly induced by clofibric acid (P4504A6) and the enzyme selectively elevated during pregnancy (P 4504A4) both exhibit relatively high rates for the omega-hydroxylation of arachidonic acid. Expand
Cytochrome P450 IIIA1 (P450p) requires cytochrome b5 and phospholipid with unsaturated fatty acids.
The ability to replace microsomal lipid extract with several different phospholipids suggests that the nature of the polar group is not critical for P450 IIIA1 activity, which implies that P 450 III1 activity is highly dependent on the fatty acid component of these lipids. Expand
19(S)-hydroxyeicosatetraenoic acid is a potent stimulator of renal Na+-K+-ATPase.
The formation of 19(S)-hydroxyeicosatetraenoic acid by renal cortical cytochrome P450 omega-1-hydroxylase may contribute to the regulation of renal function by regulating Na+-K+-ATPase which is essential for transtubular transport processes. Expand
Prostaglandin-metabolizing enzymes during pregnancy: characterization of NAD(+)-dependent prostaglandin dehydrogenase, carbonyl reductase, and cytochrome P450-dependent prostaglandin omega-hydroxylase.
  • R. Okita, J. Okita
  • Chemistry, Medicine
  • Critical reviews in biochemistry and molecular biology
  • 1996
Three prostaglandin-metabolizing enzymes induced during pregnancy are NAD(+)-dependent 15-hydroxyprostaglandsin dehydrogenase (PGDH), NADPH-dependent carbonyl reductase, and cytochrome P450-dependent prostag landin omega- or 20-hydroxylase. Expand
20-Hydroxyeicosatetraenoic acid is an endogenous vasoconstrictor of canine renal arcuate arteries.
The results indicate that 20-HETE is an endogenous constrictor of canine renal arcuate arteries and suggests a potential role for this substance in the regulation of renal vascular tone. Expand
Roles of Cytochrome b5in the Oxidation of Testosterone and Nifedipine by Recombinant Cytochrome P450 3A4 and by Human Liver Microsomes
Abstract NADH-dependent testosterone 6β-hydroxylation and nifedipine oxidation activities could be reconstituted in systems containing cytochrome b5(b5), NADH–b5reductase, and bacterial recombinantExpand
The effects of cytochrome b5, NADPH-P450 reductase, and lipid on the rate of 6 beta-hydroxylation of testosterone as catalyzed by a human P450 3A4 fusion protein.
It is proposed that the stimulation of NADPH oxidation observed following the addition of testosterone to the fusion protein may serve as a useful means of monitoring the interaction of other substrates with this P450 and thereby permit the rapid screening of chemicals to evaluate their potential metabolism by a human P450. Expand
Mechanism-based inhibitors of prostaglandin omega-hydroxylase: (R)- and (S)-12-hydroxy-16-heptadecynoic acid and 2,2-dimethyl-12-hydroxy-16-heptadecynoic acid.
2,2-Dimethyl-12-hydroxy-16-heptadecynoic acid, an analogue that cannot undergo beta-oxidation, has been synthesized as a potential in vivo inhibitor of the enzyme and has been shown to inactivate the purified enzyme with KI = 4.9 microM and t1/2 = 1.0 min. Expand