The chemistry of favism-inducing compounds. The properties of isouramil and divicine and their reaction with glutathione.
Isouramil and divicine are pyrimidine aglycones of two glucosides found in broad beans. They have been shown to be strong reducing agents. Their reaction with oxygen in a (gas) saturated solution, 26 degrees C, is characterized by tau 1/2 = 1 min and 3 min respectively. Hydrogen peroxide is formed in this reaction stoichiometrically (1:1). The pyrimidines lose two hydrogen and form an intermediate that is structurally analogues to alloxan. This intermediate is not stable, and in the absence of reducing agents it decomposes, possibly by ring-cleavage. In the presence of reduced glutathione the intermediate is reduced and can now react with oxygen once again. Thus, the pyrimidines cycle between the two states and the net reaction is the catalytic oxidation of glutathione by molecular oxygen; in each cycle 4 molecules of glutathione are dissipated. The possible involvement of these pyrimidines in the pathogenesis of favism may be in a similar mechanism. Red blood cells deficient in glucose-6-phosphate dehydrogenase cannot cope with such an oxidative challenge exerted by the pyrimidines. Consequently an irreversible cellular damage can take place leading to the enhanced sequestration of these red blood cells by the reticuloendothelial system.
D000818:Animals; D001463:Barbiturates / Q000378:metabolism*; D055598:Chemical Phenomena; D002621:Chemistry; D004912:Erythrocytes / Q000187:drug effects; D005236:Favism / Q000139:chemically induced; D005609:Free Radicals; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D010084:Oxidation-Reduction; D011744:Pyrimidinones / Q000378:metabolism*
D001463:Barbiturates; D005609:Free Radicals; D011744:Pyrimidinones; C026511:divicine; C032211:isouramil; D005978:Glutathione