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- W2078809310 abstract "Sulfur mustard is a chemical warfare agent that causes blistering of the skin and damages the eyes and airway after environmental exposure. We have previously reported that thiodiglycol (TDG, 2,2′-bis-thiodiethanol), the hydrolysis product of sulfur mustard, is oxidized by alcohol dehydrogenase (ADH) purified from horse liver or present in mouse liver and human skin cytosol. Humans express four functional classes of ADH composed of several different isozymes, which vary in their tissue distribution, some occurring in skin. To help us evaluate the potential contribution of the various human isozymes toward toxicity in skin and in other tissues, we have compared the catalytic activity of purified human class I αα-, β1β1-, β2β2-, and γ1γ1-ADH, class II π-ADH, class III χ-ADH, and class IV σ-ADH with respect to TDG oxidation and their relative sensitivities to inhibition by pyrazole. Specific activities toward TDG were 123, 79, 347, 647, and 12 nmol/min/mg for the class I αα-, β1β1-, β2β2-, and γ1γ1-ADH and class II π-ADH, respectively. TDG was not a substrate for class III χ-ADH. The specific activity of class IV σ-ADH was estimated at about 1630 nmol/min/mg. 1 mM pyrazole, a potent inhibitor of class I ADH, inhibited the class I αα, β1β1, β2β2, and γ1γ1 ADH and class IV σ-ADH by 83, 100, 56, 90, and 73%, respectively. The class I αα- and β1β1-ADH oxidized TDG with kcat/Km value of 7–8 mM−1 min−1, β2β2-ADH with a value 19 mM−1 min−1 and class I γ1γ1-ADH with a value of 176 mM−1 min−1. The kcat/Km value for class IV σ-ADH was estimated at 4 mM−1 min−1. The activities of class IV σ-ADH and class I γ1γ1-ADH are of significant interest because of their prevalence in eyes, lungs, stomach, and skin, all target organs of sulfur mustard toxicity. © 2000 John Wiley & Sons, Inc. J Biochem Toxicol 14:244–251, 2000" @default.
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- W2078809310 date "2000-01-01" @default.
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- W2078809310 title "Oxidation of thiodiglycol (2,2?-thiobis-ethanol) by alcohol dehydrogenase: Comparison of human isoenzymes" @default.
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- W2078809310 doi "https://doi.org/10.1002/1099-0461(2000)14:5<244::aid-jbt3>3.0.co;2-4" @default.
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