Possible biotransformation mechanism of 3-aminopropionitrile by means of free radicals.
The possible role of free radicals in the transformation of 3-aminopropionitrile giving rise to the liberation of cyanide was studied. Rat liver homogenates were cellularly fractionated. It was confirmed that the transformation occurred mainly in the microsomal fraction. The different isozyme forms of cytochrome P-450 were then partially purified and their velocity and affinity constants determined. It could be deduced that the cyanide-forming activity was mainly due to the LM3C cytochrome form. Dimethylsulfoxide was a potent competitive transformation inhibitor while mannitol was a moderate one. An OH radical generator inorganic system was also shown to liberate cyanide from 3-aminopropionitrile. In view of these results, a transformation mechanism of 3-aminopropionitrile by means of OH free radicals is suggested with the formation of cyanide anion in a cell-free organic system as well as in the microsomal fraction of rat liver.
Fernandez
G M
GM
Departamento de Fisiologia, Farmacologia y Toxicologia, Facultad de Veterinaria de la Universidad de Leon, SPAIN.
Lumbreras
J M
JM
Balana
R
R
Ordonez
D
D
D000629:Aminopropionitrile / Q000493:pharmacokinetics*; D000818:Animals; D001711:Biotransformation; D002458:Cell Fractionation; D003486:Cyanides / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000302:isolation & purification; D005609:Free Radicals; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000302:isolation & purification; D008862:Microsomes, Liver / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D003486:Cyanides; D005609:Free Radicals; D007527:Isoenzymes; D000629:Aminopropionitrile; D003577:Cytochrome P-450 Enzyme System