Activation of Pulmonary Carbonyl Reductase by Aromatic Amines and Pyridine Ring-Containing Compounds

Abstract

Lung of mice, guinea-pigs and pigs contains a tetrameric carbonyl reductase composed of Mr 24,000 subunits which is specifically localized in some epithelial cells of bronchus and alveolus (Nakayama et al., 1982; 1986; Matsuura et al., 1990; Oritani et al., 1992). The pulmonary enzyme has the following outstanding features which are different from those of the monomeric and dimeric enzymes in the other tissues (Sawada et al., 1979; Wermuth 1981; Hara et al., 1982; 1986; Nakayama et al., 1985; Iwata et al., 1990). The lung enzyme shows broad specificity and relatively high affinity for aliphatic and aromatic carbonyl compounds with either NADPH or NADH as a cofactor and is inhibited by pyrazole. Furthermore, it oxidizes secondary alcohols (Nakayama et al., 1986; Matsuura et al., 1988; 1989), and mediates the dismutation of aldehydes to the corresponding acids (Matsuura et al., 1989; Hara et al., 1991). Therefore, this enzyme has been suggested to play important roles in pulmonary metabolism of xenobiotic and endogenous carbonyl compounds.