The metabolism and bioactivation of agaritine and of other mushroom hydrazines by whole mushroom homogenate and by mushroom tyrosinase

Whole homogenates of Agaricus bisporus metabolised the mushroom hydrazine a garitine [beta -N-(gamma -L(+)glutamyl)-4-(hydroxymethyl) phenylhydrazine] to generate at least three metabolites. None of these metabolites, however, was the free hydrazine [4-(hydroxymethyl)phenylhyrazine]. the postulated m etabolite of agaritine believed to be formed as a result of the loss of the gamma -glutamyl group, the reaction being catalysed by gamma -glutamyltran sferase. The three metabolites of agaritine displayed weak mutagenic activi ty towards Salmonella typhimurium strain TA104. 4-(Hydroxymethyl)phenylhydr azine, as the N ' -acetyl derivative, was metabolised by mushroom tyrosinas e to yield a number of metabolites that induced a mutagenic response in S. typhimurium TA104. Similar to N ' -acetyl-4-(hydroxymethyl)phenylhydrazine, agaritine was extensively metabolised by the mushroom tyrosinase but, in c ontrast, the structurally related N ' -acetyl-4-hydrazinobenzoic acid did n ot serve as substrate of this enzyme, implying a critical role for the hydr oxymethyl group at the para-position. Tn conclusion, the current studies ha ve demonstrated for the first lime that: (a) whole mushroom homogenates rea dily metabolise agaritine but not to the postulated 4-(hydroxymethyl)phenyl hydrazine; and (b) mushroom tyrosinase metabolises agaritine and N ' -acety l-4-(hydroxymethyl)phenylhydrazine in the latter case forming genotoxic met abolites. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.