Lung carbonyl reductase in the mouse: biochemical and catalytic properties.
Two major forms of aldehyde reductase (AHR) activity were resolved following zone electrophoresis of mouse lung homogenates and distinguished by their differential substrate and inhibitor specificities: alcohol dehydrogenase (ADH) C2 and carbonyl reductase (CBR). CBR was purified to homogeneity by DEAE-cellulose chromatography, affinity chromatography using Blue-sepharose, followed by gel filtration on Sephacryl S-200. The enzyme exhibited a native MW of 122,000, comprising 4 identical subunits. Kinetic and inhibition characteristics resembled those reported by Nakayama and coworkers (1982) for guinea pig lung CBR. Mouse lung CBR exhibited optimal activity at pH 5.0; a preference for NADPH as coenzyme, although reactive with NADH at an order of magnitude higher concentration; poor activity as an ADH, but was strongly inhibited by 4-methyl pyrazole; and was inhibited by quercitin, dithiothreitol and p-OH-mercuribenzoate, but was insensitive to valproate or sorbinil. These properties, coupled with the activity of CBR with a range of aliphatic and aromatic aldehydes, ketones and quinones, distinguish it from other AHRs. The unique localization in lung tissue suggests a possible role for CBR in the detoxification of xenobiotics and of toxic aldehydes derived from lipid peroxidation processes.
Moxon
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Holmes
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D000429:Alcohol Oxidoreductases / Q000302:isolation & purification / Q000378:metabolism*; D000818:Animals; D007700:Kinetics; D008168:Lung / Q000201:enzymology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008970:Molecular Weight; D013379:Substrate Specificity
D000429:Alcohol Oxidoreductases; C019642:alcohol dehydrogenase (NADP+)