In vivo metabolism of the cardiovascular toxin, allylamine.
Previous evidence from this laboratory demonstrated that allylamine, a known cardiovascular toxin, is metabolized in vitro to acrolein, which has been hypothesized to act as a distal toxin. In this study, 3-hydroxypropylmercapturic acid was isolated and identified by MS, NMR, and 2D-NMR spectroscopy as the sole urinary metabolite of allylamine metabolism in vivo. Parallel experiments showed reduced glutathione (GSH) depletion in several organs (most marked in aorta, blood, and lung), which is consistent with GSH conjugation of the proposed acrolein intermediate. These findings indicate that allylamine was metabolized in vivo to a highly reactive aldehyde which was converted to a mercapturic acid through a GSH conjugation pathway; the exact mechanisms of cellular damage remain unclear.
Department of Pathology, University of Texas Medical Branch, Galveston 77550.
P J
PJ
Boor
R
R
Sanduja
T J
TJ
Nelson
G A
GA
Ansari
D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000652:urine; D000171:Acrolein / Q000378:metabolism; D000499:Allylamine / Q000378:metabolism* / Q000493:pharmacokinetics; D000588:Amines / Q000378:metabolism*; D000818:Animals; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D005978:Glutathione / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D051381:Rats
D000588:Amines; D000499:Allylamine; D000171:Acrolein; D005978:Glutathione; D000111:Acetylcysteine