Formation of N-nitrosoiminodialkanoic acids and their unsuitability as biological monitors for endogenous nitrosation of dipeptides.

Abstract

Nitrosation of dipeptides which do not contain imino acids leads to rearrangement and the formation of N-nitrosoiminodialkanoic acids. The optimum conditions for the nitrosation of dipeptides in buffer solutions occur at pH 2.0 (0.8-3.2% yield) and are not significantly catalysed by thiocyanate. In vitro nitrosation in gastric juice resulted in a lower yield. It was demonstrated that under normal gastric conditions, a maximum yield of 0.1 mumol total N-nitrosoiminodialkanoic acids/0.1 mol dipeptide would occur, 0.1 mol representing a typical dietary intake of dipeptide. This corresponds to a total concentration of approximately 20 micrograms/l N-nitrosoiminodialkanoic acids over a 24 h period. However, this figure may be significantly altered due to the fluctuation of nitrosation catalysts and inhibitors in gastric juice. Further studies showed that N-nitrosoiminodialkanoic acids are quantitatively excreted in urine when fed by gavage to rats. However, co-administration of the precursor dipeptide and nitrite resulted in negligible in vivo formation. The presence of N-nitrosoiminodialkanoic acids in normal human urine was not detected. Thus it was concluded that the monitoring of N-nitrosoiminodialkanoic acids in human urine is not a suitable method for biological monitoring of the endogenous nitrosation of dipeptides.