Adrenal cortical 11[beta]-hydroxylase and side-chain cleavage enzymes. requirement for the A- or B-pyridyl ring in metyrapone for inhibition
dc.contributor.author | Tobes, Michael C. | en_US |
dc.contributor.author | Hays, Sheryl J. | en_US |
dc.contributor.author | Gildersleeve, David L. | en_US |
dc.contributor.author | Wieland, Donald M. | en_US |
dc.contributor.author | Beierwaltes, William H. | en_US |
dc.date.accessioned | 2006-04-07T19:12:43Z | |
dc.date.available | 2006-04-07T19:12:43Z | |
dc.date.issued | 1985-01 | en_US |
dc.identifier.citation | Tobes, Michael C., Hays, Sheryl J., Gildersleeve, David L., Wieland, Donald M., Beierwaltes, William H. (1985/01)."Adrenal cortical 11[beta]-hydroxylase and side-chain cleavage enzymes. requirement for the A- or B-pyridyl ring in metyrapone for inhibition." Journal of Steroid Biochemistry 22(1): 103-110. <http://hdl.handle.net/2027.42/25836> | en_US |
dc.identifier.uri | http://www.sciencedirect.com/science/article/B73GT-47KPK50-1G/2/476e569b83ce4146fc05a24de46780e8 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/25836 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=3871878&dopt=citation | en_US |
dc.description.abstract | The adrenal cortical enzyme systems, 11[beta]-hydroxylase, P-45011[beta], and the side-chain cleavage complex, P-450 sec, differ only in their cytochrome P-450s. Structural modifications of metyrapone, an inhibitor of cytochrome P-450 enzyme systems, have been made to determine the requirement for the A- or B-pyridyl ring for inhibition of P-45011[beta] and P-450 scc activities. Three new analogs of metyrapone (A-phenylmetyrapone, B-phenylmetyrapone and diphenylmetyrapone) were synthesized and evaluated as inhibitors using a crude, defatted bovine adrenal cortical mitochondrial preparation. Characterization of the mitochondrial preparation demonstrated: (1) enhancement of both activities by the addition of 15.0 [mu]M adrenodoxin, (2) the addition of 1% ethanol decreased both activities less than 10%, and (3) the apparent Km of deoxycorticosterone for P-45011[beta] was 6.8 [mu]M and the apparent Km of cholesterol for P-450 scc was 21.6 [mu]M. Inhibition of P-45011[beta] and P-450 scc activities with these compounds demonstrated: (1) the B-pyridyl ring of metyrapone is required for inhibition of both activities whereas requirement for the A-ring is less stringent, and (2) the four metyrapone analogs were more selective inhibitors of P-45011[beta] activity. These studies suggest that the A-phenyl metyrapone analog is a good candidate for further development of a selective adrenocortical radiopharmaceutical. | en_US |
dc.format.extent | 955703 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.language.iso | en_US | |
dc.publisher | Elsevier | en_US |
dc.title | Adrenal cortical 11[beta]-hydroxylase and side-chain cleavage enzymes. requirement for the A- or B-pyridyl ring in metyrapone for inhibition | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Public Health | en_US |
dc.subject.hlbsecondlevel | Chemistry | en_US |
dc.subject.hlbsecondlevel | Chemical Engineering | en_US |
dc.subject.hlbsecondlevel | Biological Chemistry | en_US |
dc.subject.hlbtoplevel | Engineering | en_US |
dc.subject.hlbtoplevel | Science | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Division of Nuclear Medicine, Department of Internal Medicine, The University of Michigan Medical Center, Ann Arbor, MI 48109, U.S.A. | en_US |
dc.contributor.affiliationum | Division of Nuclear Medicine, Department of Internal Medicine, The University of Michigan Medical Center, Ann Arbor, MI 48109, U.S.A. | en_US |
dc.contributor.affiliationum | Division of Nuclear Medicine, Department of Internal Medicine, The University of Michigan Medical Center, Ann Arbor, MI 48109, U.S.A. | en_US |
dc.contributor.affiliationum | Division of Nuclear Medicine, Department of Internal Medicine, The University of Michigan Medical Center, Ann Arbor, MI 48109, U.S.A. | en_US |
dc.contributor.affiliationum | Division of Nuclear Medicine, Department of Internal Medicine, The University of Michigan Medical Center, Ann Arbor, MI 48109, U.S.A. | en_US |
dc.identifier.pmid | 3871878 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/25836/1/0000399.pdf | en_US |
dc.identifier.doi | http://dx.doi.org/10.1016/0022-4731(85)90148-7 | en_US |
dc.identifier.source | Journal of Steroid Biochemistry | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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