Ethyl carbamate metabolism: in vivo inhibitors and in vitro enzymatic systems
Yamamoto, T; Pierce, WM, Jr; Hurst, HE; Chen, D; Waddell, WJ
| HERO ID | 65374 |
|---|---|
| In Press | No |
| Year | 1990 |
| Title | Ethyl carbamate metabolism: in vivo inhibitors and in vitro enzymatic systems |
| Authors | Yamamoto, T; Pierce, WM, Jr; Hurst, HE; Chen, D; Waddell, WJ |
| Journal | Drug Metabolism and Disposition |
| Volume | 18 |
| Issue | 3 |
| Page Numbers | 276-280 |
| Abstract | The enzymatic system involved in the metabolism of ethyl-carbamate (51796) (EC) was investigated. Male Aax-mice, pretreated with agents capable of affecting EC metabolism, were given a single oral dose of 125 micromoles carbon-14 tagged EC per kilogram of body weight. Two hours after exposure, blood specimens and livers were harvested postmortem, and radioactivity in blood and covalent binding to liver protein were measured. In-vitro metabolism of ethyl-carbamate by esterase activity, measured by carbon-dioxide degeneration, was evaluated in mouse liver homogenate. Several compounds caused significant persistence of radioactivity in blood at 2 hours after exposure including: carbon-tetrachloride (56235), paraoxon (311455), ethanol (64175), methimazole (60560), 4-methylpyrazole (7554656), diethyl-maleate (141059), N-hydroxyethyl-carbamate (589413), and t-butyl-carbamate. Blood radioactivity and covalent liver protein binding were inversely proportional. Esterase activity was noted with porcine liver esterase, baker's yeast aldehyde-dehydrogenase, and mouse liver catalase; no activity was observed with canine or bovine liver catalase, acid-phosphatase, yeast alcohol-dehydrogenase, or carbonic-anhydrase. Activity inhibition toward p-nitrophenyl-acetate (830035) in mouse liver homogenate and porcine liver-esterase was similar with ethanol, paraoxon, p-nitrophenyl-acetate, 4-methylpyrazole, carbaryl (63252), and sodium-fluoride (7681494); these agents similarly inhibited EC metabolism. The ability of EC metabolism coincided with the activity to hydrolyze p-nitrophenyl-acetate. The authors conclude that EC is apparently metabolized in mouse liver by esterases. |
| Pmid | 1974186 |
| Wosid | WOS:A1990DG27700004 |
| Is Certified Translation | No |
| Dupe Override | No |
| Comments | Drug Metab. Dispos. 18: 276-280. Scopus URL: https://www.scopus.com/inward/record.uri?eid=2-s2.0-0025344864&partnerID=40&md5=9f85c2704dbc93913e3b792d7f61862b |
| Is Public | Yes |
| Language Text | English |
| Keyword | <?xml version="1.0" encoding="UTF-8"?><kw>DCN-190585</kw>; <?xml version="1.0" encoding="UTF-8"?><kw>Carbamates</kw>; <?xml version="1.0" encoding="UTF-8"?><kw>Enzyme activity</kw>; <?xml version="1.0" encoding="UTF-8"?><kw>In vitro studies</kw>; <?xml version="1.0" encoding="UTF-8"?><kw>Liver enzymes</kw>; <?xml version="1.0" encoding="UTF-8"?><kw>In vivo studies</kw>; <?xml version="1.0" encoding="UTF-8"?><kw>Laboratory animals</kw>; <?xml version="1.0" encoding="UTF-8"?><kw>Metabolic study</kw>; <?xml version="1.0" encoding="UTF-8"?><kw>Oxidative metabolism</kw> |
| Is Qa | No |