K. Walton et al., The metabolism and bioactivation of agaritine and of other mushroom hydrazines by whole mushroom homogenate and by mushroom tyrosinase, TOXICOLOGY, 161(3), 2001, pp. 165-177
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.