Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.10.3.1 (tyrosinase)
 9,065 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Agaritine (N2-[L-(+)-glutamyl]-4-(hydroxymethylphenyl)hydrazine), the principal hydrazine found in the edible mushroom Agaricus bisporus, as well as the N'-acetyl derivative of 4-(hydroxymethyl)phenylhydrazine and 4-(hydroxymethyl)benzene diazonium ion, as the tetraborate salt, considered as the putative proximate and ultimate carcinogens of agaritine, were all synthesised chemically. The mutagenicity of these compounds and of 4-hydrazinobenzoic acid, a precursor of agaritine biosynthesis in mushroom, was investigated in the Ames test, using Salmonella typhimurium strain TA104, in the absence and in the presence of either mushroom tyrosinase or rat hepatic cytosol as activation systems. In the absence of an activation system the diazonium ion was clearly the most mutagenic of the four compounds studied. When tyrosinase was used as activation system, the mutagenicity of N'-acetyl-4-(hydroxymethyl)phenylhydrazine was enhanced; glutathione and superoxide dismutase markedly suppressed the mutagenic response. When the mutagenicity of the four compounds was evaluated in the presence of rat hepatic cytosol, an increase was seen only in the case of N'-acetyl-4-(hydroxymethyl)phenylhydrazine; this was shown to be due to deacetylation releasing the more mutagenic free hydrazine. Collectively, the above data are compatible with an activation of agaritine that involves an initial loss of the gamma-glutamyl group followed by microsomal oxidation of the free hydrazine to generate the diazonium ion. Also of interest is the observation that mushroom tyrosinase can convert N'-acetyl-4-(hydroxymethyl)phenylhydrazine to mutagenic product(s); whether these products contribute to the mutagenicity of mushroom extracts remains to be established.
 ...
PMID:Bioactivation of mushroom hydrazines to mutagenic products by mammalian and fungal enzymes. 940 39

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.
 ...
PMID:The metabolism and bioactivation of agaritine and of other mushroom hydrazines by whole mushroom homogenate and by mushroom tyrosinase. 1129 5