The activity of dehydropeptidase I in rat tissues decreases in the order of lung > kidney > liver-spleen > other tissues, while aminopeptidase activity is high in the kidney, and lower in the lung than in other tissues.Dehydropeptidase I was solubilized from the membrane fraction of rat lung by treatment with papain and purified by DEAE-cellulose column chromatography, affinity chromatography on concanavalin-A-Sepharose and highperformance liquid chromatography gel filtration. The purified preparation was found to be homogeneous on sodium dodecyl sulfate/polyacrylamide gel electrophoresis. The relative molecular mass was estimated to be 150000 by gel filtration, comprising a homodimer of two 80000-Mr subunits. The enzyme activity was inhibited by cilastatin, o-phenanthroline and ATP. This enzyme catalyzed the hydrolysis of S(substituent)-L-cysteinyl-glycine adducts such as L-cystinyLbis(g1ycine) and N-ethylmaleimide-S-L-cysteinyl-glycine, as well as the conversion of leukotriene D4 to F4. Furthermore it catalyzed a hydrolytic splitting of L-Leu-L-Leu, but not S-benzyl-L-cysteine p-nitroanilide, which is a good substrate for aminopeptidase. Our enzyme preparation was immunologically identical to the rat renal dehydropeptidase I. The physiological significance of the pulmonary dehydropeptidase I on the metabolism of glutathione and its adducts is discussed.The degradation of reduced and oxidized glutathione and of glutathione adducts is initiated by y-glutamyl transferase [l , 21, which removes the y-glutamyl moiety to form L-cysteinylglycine(L-Cys-Gly), L-cystinyl-bis(g1ycine) (~-m y s -G l y J and S (substituent)-L-Cys-Gly adducts, respectively. These dipeptides or dipeptide adducts are further hydrolyzed by dipeptidases or by aminopeptidase M [3,4].Campbell et al. purified the dipeptidase hydrolyzing glycyl-dehydrophenylalanine from porcine [S -71 and human [8] kidneys. Recently, it has been reported that this enzyme specifically hydrolyzes the dehydropeptide bond in carbapenem antibiotics, and it has been referred to as dehydrope tiddse I (DHP-I) [9, 101. We have previously shown that L-h ys ys-Gly, and S(substituent)-L-Cys-Gly adducts are mainly hydrolyzed by the renal DHP-I rather than by aminopeptidase M, and we suggested that DHP-I is an important enzyme in the metabolism of glutathione and glutathione adducts [Ill.In the present study, the tissue distribution of activities of DHP-I and aminopeptidase in rats was investigated, and DHP-I was purified from the rat lung, where its specific activity was found to be higher than in the kidney. The immunological identity between pulmonary and renal DHP-I was also compared using anti-(renal DHP-I) antibody.

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Male rats more than seven weeks old showed significantly higher activity of hepatic cytosolic glutathione S-transferase (GST) than females. This sex-related difference in GST activities might be explained by the difference in subunit composition of the enzymes between males and females. The relative proportion of subunit composition of GST between adult male and female rats was as follows: Ya, female greater than male; Yb(Yb'), male much greater than female; Yc, female greater than male. Since phenobarbital (60 mg/kg, i.p. for seven days) induced the Yb subunit as well as Ya subunit, the enzyme activity was more increased in males than in females and the sex difference became more marked. 3-Methylcholanthrene (20 mg/kg, i.p. three times) caused an increase of Ya subunit alone, and then the increased extent was greater in females than in males, and resulted in the disappearance of sex difference.

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