Publication Date:
1986-12-05
Description:
Cortisol production requires the activity of only 17 alpha-hydroxylase, whereas the formation of sex steroids requires both 17 alpha-hydroxylase and 17,20-lyase activities. Studies in reconstituted enzyme systems have suggested that a single steroid hydroxylase, 17 alpha-hydroxylase cytochrome P-450 (P-450(17) alpha), catalyzes both activities. By expression of bovine adrenocortical P-450(17 alpha) in COS 1 (transformed monkey kidney) cells, which normally contain no detectable P-450(17) alpha, it has now been established in situ that a single polypeptide chain does catalyze both the 17 alpha-hydroxylase and the 17,20-lyase reactions. This heterologous system supports 17 alpha-hydroxylation of pregnenolone and progesterone with equal efficiency, but catalyzes about five times as much 17,20-lyase activity when 17 alpha-hydroxypregnenolone is the substrate than when 17 alpha-hydroxyprogesterone is the substrate. For these activities to be observed in COS 1 cells, newly synthesized apocytochrome P-450(17) alpha must bind heme and insert into the endoplasmic reticulum such that endogenous cytochrome P-450 reductase can support hydroxylation. Thus, COS 1 cells are a useful system for expression and study of various forms of cytochrome P-450.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zuber, M X -- Simpson, E R -- Waterman, M R -- 5-T 32HD07190/HD/NICHD NIH HHS/ -- AM 238350/AM/NIADDK NIH HHS/ -- HD 13234/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 1986 Dec 5;234(4781):1258-61.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3535074" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Cattle
;
Cercopithecus aethiops
;
Cytochrome P-450 Enzyme System/genetics/*metabolism
;
DNA/*metabolism
;
Fluorescent Antibody Technique
;
Kidney/cytology
;
Multienzyme Complexes/genetics/metabolism
;
Pregnenolone/metabolism
;
Progesterone/metabolism
;
Steroid 17-alpha-Hydroxylase/*metabolism
;
Steroid Hydroxylases/genetics/*metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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