Oxidation of the 2-hydroxyamino derivative of 2-amino-6-methyl-dipyrido[1,2-a: 3',2'-d] imidazole (Glu-P-1) to its 2-nitroso form, an ultimate form reacting with hemoglobin thiol groups

Biochem Biophys Res Commun. 1988 Mar 30;151(3):1326-31. doi: 10.1016/s0006-291x(88)80507-2.

Abstract

The binding to hemoglobin of synthetic 2-hydroxyamino-6-methyldipyrido[1,2-a: 3',2'-d] imidazole from the carcinogenic product of L-glutamic acid pyrolysis 2-amino-6-methyldipyrido[1,2-a: 3',2'-d] imidazole were investigated in vitro. The hydroxylamine required oxidation to its nitroso derivative to bind to rat hemoglobin through thiol groups. Oxidation of the hydroxylamine to the nitroso form was found to be enhanced by oxyhemoglobin and superoxide dismutase at pH 7.4 under aerobic conditions. Since these conditions might also enhance this oxidation in vivo, the conversion of the DNA-reactive arylhydroxylamines to the DNA-non-reactive nitroso compounds and their subsequent binding to highly abundant thiol groups of proteins could be considered as a process for detoxification of toxic arylhydroxylamines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Hemoglobins / metabolism*
  • Hydrogen-Ion Concentration
  • Imidazoles / metabolism*
  • Male
  • Oxyhemoglobins / metabolism
  • Rats
  • Rats, Inbred F344
  • Sulfhydryl Compounds / metabolism
  • Superoxide Dismutase / metabolism

Substances

  • Hemoglobins
  • Imidazoles
  • Oxyhemoglobins
  • Sulfhydryl Compounds
  • 2-amino-6-methyldipyrido(1,2-a-3',2'-d)imidazole
  • Superoxide Dismutase