Blog
About

10
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: not found
      • Article: not found

      Human Cytochrome P450 Enzymes: A Status Report Summarizing Their Reactions, Substrates, Inducers, and Inhibitors

      ,

      Drug Metabolism Reviews

      Informa UK Limited

      Read this article at

      ScienceOpenPublisher
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Related collections

          Most cited references 128

          • Record: found
          • Abstract: found
          • Article: not found

          P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature.

          We provide here a list of 481 P450 genes and 22 pseudogenes, plus all accession numbers that have been reported as of October 18, 1995. These genes have been described in 85 eukaryote (including vertebrates, invertebrates, fungi, and plants) and 20 prokaryote species. Of 74 gene families so far described, 14 families exist in all mammals examined to date. These 14 families comprise 26 mammalian subfamilies, of which 20 and 15 have been mapped in the human genome and the mouse genome, respectively. Each subfamily usually represents a cluster of tightly linked genes widely scattered throughout the genome, but there are exceptions. Interestingly, the CYP51 family has been found in mammals, filamentous fungi and yeast, and plants-attesting to the fact that this P450 gene family is very ancient. One functional CYP51 gene and two processed pseudogenes, which are the first examples of intronless pseudogenes within the P450 superfamily, have been mapped to three different human chromosomes. This revision supersedes the four previous updates in which a nomenclature system, based on divergent evolution of the superfamily, has been described. For the gene, we recommend that the italicized root symbol "CYP' for human ("Cyp' for mouse and Drosophila), representing "cytochrome P450', be followed by an Arabic number denoting the family, a letter designating the subfamily (when two or more exist), and an Arabic numeral representing the individual gene within the subfamily. A hyphen is no longer recommended in mouse gene nomenclature. "P' ("ps' in mouse and Drosophila) after the gene number denotes a pseudogene; "X' after the gene number means its use has been discontinued. If a gene is the sole member of a family, the subfamily letter and gene number would be helpful but need not be included. The human nomenclature system should be used for all species other than mouse and Drosophila. The cDNAs, mRNAs and enzymes in all species (including mouse) should include all capital letters, and without italics or hyphens. This nomenclature system is similar to that proposed in our previous updates.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Steroidogenic enzymes: structure, function, and role in regulation of steroid hormone biosynthesis.

             I Hanukoglu (1992)
            In the pathways of steroid hormone biosynthesis there are two major types of enzymes: cytochromes P450 and other steroid oxidoreductases. This review presents an overview of the function and expression of both types of enzymes with emphasis on steroidogenic P450s. The final part of the review on regulation of steroidogenesis includes a description of the normal physiological fluctuations in the steroid output of adrenal cortex and gonads, and provides an analysis of the relative role of enzyme levels in the determination of these fluctuations. The repertoire of enzymes expressed in a steroidogenic cell matches the cell's capacity for the biosynthesis of specific steroids. Thus, steroidogenic capacity is regulated mainly by tissue and cell specific expression of enzymes, and not by selective activation or inhibition of enzymes from a larger repertoire. The quantitative capacity of steroidogenic cells for the biosynthesis of specific steroids is determined by the levels of steroidogenic enzymes. The major physiological variations in enzyme levels, are generally associated with parallel changes in gene expression. The level of expression of each steroidogenic enzyme varies in three characteristics: (a) tissue- and cell-specific expression, determined during tissue and cell differentiation; (b) basal expression, in the absence of trophic hormonal stimulation; and (c) hormonal signal regulated expression. Each of these three types of expression probably represent the functioning of distinct gene regulatory elements. In adult steroidogenic tissues, the levels of most of the cell- and tissue-specific steroidogenic enzymes depend mainly on trophic hormonal stimulation mediated by a complex network of signal transduction systems. Copyright © 1992. Published by Elsevier Ltd.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Molecular cloning and expression of CYP2J2, a human cytochrome P450 arachidonic acid epoxygenase highly expressed in heart.

              A cDNA encoding a human cytochrome P450 arachidonic acid epoxygenase was isolated from a human liver cDNA library. Sequence analysis revealed that this 1,876-base pair cDNA contained an open reading frame and encoded a new 502-amino acid protein designated CYP2J2. Blot hybridization analysis of RNA prepared from human tissues revealed that CYP2J2 was highly expressed in the heart. Recombinant CYP2J2 protein was prepared using the baculovirus expression system and purified to near electrophoretic homogeneity. The enzyme metabolized arachidonic acid predominantly via olefin epoxidation to all four regioisomeric cis-epoxyeicosatrienoic acids (catalytic turnover 65 pmol of product formed/nmol of cytochrome P450/min at 30 degrees C). Epoxidation of arachidonic acid by CYP2J2 at the 14,15-olefin was highly enantioselective for (14R, 15S)-epoxyeicosatrienoic acid (76% optical purity). Immunoblotting of microsomal fractions prepared from human tissues using a polyclonal antibody raised against the recombinant hemoprotein confirmed primary expression of CYP2J2 protein in human heart. The in vivo significance of CYP2J2 was suggested by documenting the presence of epoxyeicosatrienoic acids in the human heart using gas chromatography/mass spectroscopy. Importantly, the chirality of CYP2J2 products matched that of the epoxyeicosatrienoic acid enantiomers present, in vivo, in human heart. We propose that CYP2J2 is one of the enzymes responsible for epoxidation of endogenous arachidonic acid pools in human heart and that epoxyeicosatrienoic acids may, therefore, play important functional roles in cardiac physiology.
                Bookmark

                Author and article information

                Journal
                Drug Metabolism Reviews
                Drug Metabolism Reviews
                Informa UK Limited
                0360-2532
                1097-9883
                February 15 2010
                February 15 2010
                : 29
                : 1-2
                : 413-580
                Article
                10.3109/03602539709037591
                © 2010

                Comments

                Comment on this article