Formation of epsilon-hydroxycaproate and epsilon-aminocaproate from N-nitrosohexamethyleneimine: evidence that microsomal alpha-hydroxylation of cyclic nitrosamines may not always involve the insertion of molecular oxygen into the substrate.
The formation of the products of microsomal metabolism of the cyclic nitrosamine, nitrosohexamethyleneimine (NO-HEX) were studied. Information on the origins of the oxygen atoms in four major metabolites of NO-HEX was obtained by metabolizing this compound in an 18O2 atmosphere using microsomes and cytosol, beta- and gamma-Hydroxy-NO-HEX are formed as a result of the insertion of a hydroxyl group derived from molecular oxygen into NO-HEX. All of the oxygen atoms in epsilon-aminocaproate (EAC) were derived from water. Approximately half of the molecules of epsilon- hydroxycaproate ( EHC ) contain an 18O atom; thus, half of the alpha-hydroxy-NO-HEX formed incorporates a hydroxyl group derived from molecular oxygen with the remainder of the hydroxyls being from water. To account for the above data and the related metabolic origins of EAC and EHC ( Hecker and McClusky , Cancer Res., 42 (1982) 59; Hecker et al., Teratogen. Carcinogen. Mutagen (1982) in press), we have proposed a mechanism for the formation of these compounds from cyclic nitrosamines catalyzed by microsomal and cytosolic enzymes.
D000614:Aminocaproates / Q000378:metabolism*; D015119:Aminocaproic Acid / Q000378:metabolism*; D000818:Animals; D002208:Caproates / Q000378:metabolism*; D002273:Carcinogens / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D003600:Cytosol / Q000201:enzymology; D006880:Hydroxy Acids; D008297:Male; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D009602:Nitrosamines / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D014867:Water / Q000378:metabolism
D000614:Aminocaproates; D002208:Caproates; D002273:Carcinogens; D006880:Hydroxy Acids; D009602:Nitrosamines; D014867:Water; C039565:6-hydroxyhexanoic acid; C002742:N-nitrosoperhydroazepine; D006899:Mixed Function Oxygenases; D010100:Oxygen; D015119:Aminocaproic Acid