Substrate specificity of rat liver aldehyde dehydrogenase with chloroacetaldehydes.
Chlorinated acetaldehydes have been the focus of research due to their role as reactive intermediates and their possible occurrence in chlorinated drinking water. This study investigated the in vitro substrate specificity of cytosolic and mitochondrial rat liver aldehyde dehydrogenase toward these compounds. Monochloroacetaldehyde was found to be extensively metabolized by these enzymes, to an even greater extent than the standard substrate propionaldehyde. Dichloroacetaldehyde was metabolized to a much lesser extent, and chloral hydrate is not metabolized by this enzyme family. The Km (mM) and Vmax (Vmax for propionaldehyde set to 100) values with the low Km cytosolic enzyme were monochloroacetaldehyde 0.046 and 582, and dichloroacetaldehyde 0.13 and 54.9, and those with the high Km cytosolic enzyme were dichloroacetaldehyde 0.35 and 23.4. The values with the low Km mitochondrial enzyme were monochloroacetaldehyde 0.057 and 462 and dichloroacetaldehyde 0.038 and 12.9, and those with the high Km mitochondrial enzyme were monocloroacetaldehyde 0.024 and 55.5 and dichloroacetaldehyde 0.29 and 3.44. These data suggest that aldehyde dehydrogenase plays a significant role in the metabolism of monochloroacetaldehyde and, to some extent, dichloroacetaldehyde. Some evidence also suggested that alcohol dehydrogenase plays a significant role in the metabolism of dichloroacetaldehyde and chloral hydrate.
Sharpe
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Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson 85721.
Carter
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D000079:Acetaldehyde / Q000031:analogs & derivatives* / Q000378:metabolism; D000444:Aldehyde Dehydrogenase / Q000378:metabolism*; D000818:Animals; D003600:Cytosol / Q000201:enzymology; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013379:Substrate Specificity
D007527:Isoenzymes; C004656:chloroacetaldehyde; D000444:Aldehyde Dehydrogenase; D000079:Acetaldehyde