Mechanism of the catalytic oxidation of adrenaline by ferritin.

The oxidation of adrenaline to the N-methylindolequinone, adrenochrome, is catalyzed by ferritin iron in the presence of Hz02 at acid pH (1). The mechanism of this reaction, which involves the intermediate formation of hydroxyl radicals and which does not require molecular oxygen, differs from that involved at neutral or slightly alkaline pH. Our present studies show that ferritin contains a portion of its total iron in a reactive state capable of catalyzing the aerobic oxidation of adrenaline to adrenochrome at pH 7.4 in the absence of added HzOz. Adrenochrome, at this pH, is rapidly converted to brown melanin-like pigments, a reaction which takes place very slowly at more acid pH. The reaction of ferritin iron with adrenaline at pH 7.4 may be of physiological significance since the constrictor response of the mesenteric precapillary blood vessels to topically applied adrenaline is inhibited (2) when ferritin is present in the circulation, necessitating the addition of higher concentrations of adrenaline to bring about a constrictor response. Our findings indicate that the oxidation of adrenaline at pH 7.4 is accompanied by a loss of its vasoconstrictor activity, suggesting that the inhibitory action of ferritin on the response of the smooth muscle cells of the mesenteric precapillaries to topical adrenaline may be a result of ferritin-catalyzed adrenaline oxidation.