Abstract:
:If liver alcohol dehydrogenase were rate-limiting in ethanol metabolism, inhibitors of the enzyme should inhibit the metabolism with the same type of kinetics and the same kinetic constants in vitro and in vivo. Against varied concentrations of ethanol, 4-methylpyrazole is a competitive inhibitor of purified rat liver alcohol dehydrogenase (Kis = 0.11 microM, in 83 mM potassium phosphate and 40 mM KCl buffer, pH 7.3, 37 degrees C) and is competitive in rats (with Kis = 1.4 mumol/kg). Isobutyramide is essentially an uncompetitive inhibitor of purified enzyme (Kii = 0.33 mM) and of metabolism in vivo (Kii = 1.0 mmol/kg). Low concentrations of both inhibitors decreased the rate of metabolism as a direct function of their concentrations. Qualitatively, therefore, alcohol dehydrogenase activity appears to be a major rate-limiting factor in ethanol metabolism. Quantitatively, however, the constants may not agree because of distribution in the animal or metabolism of the inhibitors. At saturating concentrations of inhibitors, ethanol is eliminated by inhibitor-insensitive pathways, at about 10% of the total rate at a dose of ethanol of 10 mmol/kg. Uncompetitive inhibitors of alcohol dehydrogenase should be especially useful for inhibiting the metabolism of alcohols since they are effective even at saturating levels of alcohol, in contrast to competitive inhibitors, whose action is overcome by saturation with alcohol.
journal_name
Arch Biochem Biophysjournal_title
Archives of biochemistry and biophysicsauthors
Plapp BV,Leidal KG,Smith RK,Murch BPdoi
10.1016/0003-9861(84)90083-3subject
Has Abstractpub_date
1984-04-01 00:00:00pages
30-8issue
1eissn
0003-9861issn
1096-0384pii
0003-9861(84)90083-3journal_volume
230pub_type
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journal_title:Archives of biochemistry and biophysics
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pub_type: 杂志文章
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pub_type: 杂志文章,评审
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pub_type: 杂志文章
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journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
doi:10.1006/abbi.1998.0657
更新日期:1998-06-01 00:00:00
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doi:10.1016/0003-9861(83)90349-1
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pub_type: 杂志文章
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journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
doi:10.1006/abbi.1995.1385
更新日期:1995-08-01 00:00:00
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pub_type: 杂志文章
doi:10.1006/abbi.1994.1025
更新日期:1994-01-01 00:00:00
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pub_type: 杂志文章
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更新日期:2007-05-01 00:00:00
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journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
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更新日期:1995-04-20 00:00:00
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更新日期:2019-10-30 00:00:00
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journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
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更新日期:1983-08-01 00:00:00
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journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章,评审
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更新日期:2018-07-15 00:00:00