TAILIEUCHUNG - Báo cáo Y học: Baboon cytochrome P450 17a-hydroxylase/17,20-lyase (CYP17) Characterization of the adrenal microsomal and cloned enzymes

Human cytochrome P450 17a-hydroxylase (CYP17) cata-lyses not only the 17a-hydroxlation of pregnenolone and progesterone and the C17,20-side chain cleavage (lyase) of 17a-hydroxypregnenolone, necessary for the biosynthesis of C21-glucocorticoids and C19-androgens, but also catalyses the 16a-hydroxylation of progesterone. In efforts to under-stand the complex enzymology of CYP17, structure/func-tion relationships have been reported previously after expressingrecombinant DNAs, encodingCYP17 from various species, in nonsteroidogenic mammalian or yeast cells. . | Eur. J. Biochem. 269 5608-5616 2002 FEBS 2002 doi Baboon cytochrome P450 17a-hydroxylase 17 20-lyase CYP17 Characterization of the adrenal microsomal and cloned enzymes Amanda C. Swart1 Norbert W. Kolar1 Nic Lombard1 J. Ian Mason2 and Pieter Swart1 1 Department of Biochemistry University of Stellenbosch South Africa department of Reproductive Developmental Sciences University of Edinburgh Medical School Scotland UK Human cytochrome P450 17a-hydroxylase CYP17 catalyses not only the 17a-hydroxlation of pregnenolone and progesterone and the C17 20-side chain cleavage lyase of 17a-hydroxypregnenolone necessary for the biosynthesis of C21-glucocorticoids and C19-androgens but also catalyses the 16a-hydroxylation of progesterone. In efforts to understand the complex enzymology of CYP17 structure func-tion relationships have been reported previously after expressing recombiaanl DNAs eccoding CYP17 from various species in nonsteroidogenic mammalian or yeast cells. A major difference between species resides in the lyase activity towards the hydroxylated intermediates and in the fact that the secretion of C19-steroids take place in some species principally in the gonads. Because human and higher primate adrenals secrete steroids CYP17 has been characterized in the Cape baboon a species more closely related to humans in an effort to gain a further understanding of the reactions catalysed by CYP17. Baboon and human CYP17 cDNA share 96 homology. Baboon CYP17 has apparent Km and V values for pregnenolone and progesterone of M and nmol h-1-mg protein 1 and M and nmol-h_1-mgprotein_1 respectively. Baboon CYP17 had a significantly higher activity for progesterone hydroxylation relative to pregnenolone. No 16a-hydroxylase and no lyase activity for 17a-hydroxyprogesterone. Sequence analyses showed that there are 28 different amino acid residues between human and baboon CYP17 primarily in helices F and G and the F-G loop. Keywords CYP17

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