Baboon cytochrome P450 17alpha-hydroxylase/17,20-lyase (CYP17).
Human cytochrome P450 17alpha-hydroxylase (CYP17) catalyses not only the 17alpha-hydroxlation of pregnenolone and progesterone and the C17,20-side chain cleavage (lyase) of 17alpha-hydroxypregnenolone, necessary for the biosynthesis of C21-glucocorticoids and C19-androgens, but also catalyses the 16alpha-hydroxylation of progesterone. In efforts to understand the complex enzymology of CYP17, structure/function relationships have been reported previously after expressing recombinant DNAs, encoding 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 0.9 micro m and 0.4 nmol.h-1.mg protein-1 and 6.5 micro m and 3.9 nmol.h-1.mg protein-1, respectively. Baboon CYP17 had a significantly higher activity for progesterone hydroxylation relative to pregnenolone. No 16alpha-hydroxylase and no lyase activity for 17alpha-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.
Swart
Amanda C
AC
Department of Biochemistry, University of Stellenbosch, South Africa; Department of Reproductive & Developmental Sciences, University of Edinburgh Medical School, Scotland, UK. acswart@sun.ac.za
Kolar
Norbert W
NW
Lombard
Nic
N
Mason
J Ian
JI
Swart
Pieter
P
D000311:Adrenal Glands / Q000201:enzymology*; D000818:Animals; D002248:Carbon Monoxide / Q000737:chemistry; D002384:Catalysis; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D003001:Cloning, Molecular; D003687:Dehydroepiandrosterone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007700:Kinetics; D008861:Microsomes / Q000201:enzymology*; D010100:Oxygen / Q000378:metabolism; D010215:Papio; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013254:Steroid 17-alpha-Hydroxylase / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D013256:Steroids / Q000378:metabolism; D013997:Time Factors; D014162:Transfection
D013256:Steroids; D003687:Dehydroepiandrosterone; D002248:Carbon Monoxide; D013254:Steroid 17-alpha-Hydroxylase; D010100:Oxygen