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 agaritine [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)phenylhydrazine], the postulated metabolite of agaritine believed to be formed as a result of the loss of the gamma-glutamyl group, the reaction being catalysed by gamma-glutamyltransferase. The three metabolites of agaritine displayed weak mutagenic activity towards Salmonella typhimurium strain TA104. 4-(Hydroxymethyl)phenylhydrazine, as the N'-acetyl derivative, was metabolised by mushroom tyrosinase 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 contrast, the structurally related N'-acetyl-4-hydrazinobenzoic acid did not serve as substrate of this enzyme, implying a critical role for the hydroxymethyl group at the para-position. In conclusion, the current studies have demonstrated for the first time that: (a) whole mushroom homogenates readily metabolise agaritine but not to the postulated 4-(hydroxymethyl)phenylhydrazine; and (b) mushroom tyrosinase metabolises agaritine and N'-acetyl-4-(hydroxymethyl)phenylhydrazine, in the latter case forming genotoxic metabolites.
Walton
K
K
School of Biological Sciences, Molecular Toxicology Group, University of Surrey, Guildford GU2 5XH UK.
Coombs
M M
MM
Walker
R
R
Ioannides
C
C
D000363:Agaricales / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism*; D001711:Biotransformation; D006834:Hydrazines / Q000378:metabolism / Q000493:pharmacokinetics* / Q000633:toxicity; D014442:Monophenol Monooxygenase / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity; D010659:Phenylhydrazines / Q000378:metabolism / Q000493:pharmacokinetics* / Q000633:toxicity
D006834:Hydrazines; D009153:Mutagens; D010659:Phenylhydrazines; D014442:Monophenol Monooxygenase; C015654:agaritine