Oxidation of Thiodiglycol (2,2'-Thiobis-ethanol) by Alcohol Dehydrogenase: Comparison of Human Isoenzymes
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 (AD H) 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 alphaalpha-,Beta1Beta1-,Beta2Beta2-, gamma1gamma1-ADH, class II pi-ADH, class III chi-ADH, and class IV sigma-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 alphaalpha-, beta1beta1-, beta2beta2-, and gamma1gamma1-ADH and class II sigma-ADH, respectively. TDC was not a substrate for class III chi-ADH.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2000
- Accession Number
- ADA386013
Entities
People
- A. A. Brimfield
- B. F. Dudley
- G. W. Winston
Organizations
- United States Army Medical Research Institute of Chemical Defense