Inhibition of renal ornithine decarboxylase by aminoglycoside antibiotics in vitro
dc.contributor.author | Henley, III, Charles M. | en_US |
dc.contributor.author | Mahran, Laila G. | en_US |
dc.contributor.author | Schacht, Jochen | en_US |
dc.date.accessioned | 2006-04-07T20:20:09Z | |
dc.date.available | 2006-04-07T20:20:09Z | |
dc.date.issued | 1988-05-01 | en_US |
dc.identifier.citation | Henley, III, Charles M., Mahran, Laila G., Schacht, Jochen (1988/05/01)."Inhibition of renal ornithine decarboxylase by aminoglycoside antibiotics in vitro." Biochemical Pharmacology 37(9): 1679-1682. <http://hdl.handle.net/2027.42/27327> | en_US |
dc.identifier.uri | http://www.sciencedirect.com/science/article/B6T4P-4779619-10P/2/319a90462629cee861290929fb7c9182 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/27327 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=3377830&dopt=citation | en_US |
dc.description.abstract | The inhibition of renal ornithine decarboxylase (ODC) by aminoglycoside antibiotics was characterized in the postmitochondrial fraction of a kidney homogenate from adult pigmented guinea pigs. Enzymatic activity was defined as the rate of decarboxylation of [14C]ornithine sensitive to a specific ODC inhibitor, [alpha]-difluoromethylornithine (DFMO). The Km for ornithine was 61 +/- 32 , [mu]M. There were two forms of the enzyme with respect to their affinity for pyridoxal phosphate (PLP): (I) Km = 2.1 +/- 1.8 [mu]M; (II) Km = 36.2 +/- 12.7 [mu]M. Putrescine, a known ODC inhibitor, acted competitively on the renal enzyme with Ki = 1.7 +/- 1.4 mM. Aminoglycoside antibiotics inhibited ODC by an uncompetitive mechanism with inhibitor constants of comparable magnitude: neomycin, Ki = 1.3 +/- 0.1 mM; gentamicin, Ki = 1.6 +/- 0.1 mM; kanamycin, Ki = 1.9 +/- 0.2 mM; and netilmicin, Ki = 1.7 +/- 0.2 mM. Neomycin inhibited both forms of the enzyme (low and high affinity for PLP) uncompetitively with similar inhibitor constants (1.5 +/- 0.3 and 1.8 +/- 0.4 mM respectively), suggesting a single mechanism of action. Inhibition of ODC suggests that aminoglycoside-polyamine interactions may be an important component of the sequence of biochemical events associated with aminoglycoside toxicity. | en_US |
dc.format.extent | 485669 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 | Inhibition of renal ornithine decarboxylase by aminoglycoside antibiotics in vitro | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Biological Chemistry | 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 | Kresge Hearing Research Institute, University of Michigan, Ann Arbor, MI 48109, U.S.A. | en_US |
dc.contributor.affiliationum | Kresge Hearing Research Institute, University of Michigan, Ann Arbor, MI 48109, U.S.A. | en_US |
dc.contributor.affiliationum | Kresge Hearing Research Institute, University of Michigan, Ann Arbor, MI 48109, U.S.A. | en_US |
dc.identifier.pmid | 3377830 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/27327/1/0000350.pdf | en_US |
dc.identifier.doi | http://dx.doi.org/10.1016/0006-2952(88)90427-3 | en_US |
dc.identifier.source | Biochemical Pharmacology | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
Files in this item
Remediation of Harmful Language
The University of Michigan Library aims to describe library materials in a way that respects the people and communities who create, use, and are represented in our collections. Report harmful or offensive language in catalog records, finding aids, or elsewhere in our collections anonymously through our metadata feedback form. More information at Remediation of Harmful Language.
Accessibility
If you are unable to use this file in its current format, please select the Contact Us link and we can modify it to make it more accessible to you.