IRON-DEPENDENT AND PEROXIDE-DEPENDENT CONJUGATION OF DOPAMINE WITH CYSTEINE - OXIDATIVE ROUTES TO THE NOVEL BRAIN METABOLITE 5-S-CYSTEINYLDOPAMINE

The mechanism of formation of 5-S-cysteinyldopamine (5-S-CDA), a putat ive index of oxidative stress in dopaminergic regions of the brain, wa s investigated by comparing the ability of a number of neurochemically relevant oxidising systems to promote the conjugation of dopamine wit h cysteine in vitro. Autoxidation of the catecholamine proceeds at rel atively slow rate in the physiological pH range, and is little affecte d by 1 mM Fe2+-EDTA complex. In the presence of cysteine, however, the Fe2+-induced autoxidation is hastened, affording little amounts of 5- S-CDA. Formation of the adduct is completely suppressed by ascorbic ac id. Hydrogen peroxide, in the presence of Fe2+-EDTA (Fenton-type oxida tion) or peroxidase, promotes a relatively efficient conversion of dop amine to 5-S-CDA and the minor isomer 2-S-CDA. Noteworthy, 15-hydroper oxyeicosatetraenoic acid (arachidonic acid hydroperoxide, HPETE), in t he presence of Fe2+-EDTA complex, can also mediate 5-S-CDA formation, whilst superoxide radicals are little effective. Overall, these result s suggest that ferrous ions, hydrogen peroxide and lipoperoxides may p lay an important role in 5-S-CDA generation.