N-methyl-N-formylhydrazine: A toxic and mutagenic inhibitor of the intestinal diamine oxidase

Abstract

N-methyl-N-formylhydrazine is the first active intermediate of the poison gyromitrin of the mushroom: false morel. This compound is a non-competitive inhibitor of human intestinal diamine oxidase (ID50 = 1.6 X 10(-5) mol/l). This concentration corresponds to less than 5 g of wet weight of mushroom/l. The diamine oxidases from 5 other sources are inhibited in a similar manner. Semicarbazide and aminoguanidine are 10-respectively 1000-fold more potent inhibitors of the human intestinal diamine oxidase. An involvement of the diamine oxidase inhibitory property of N-methyl-N-formylhydrazine in toxic and mutagenic effects of the substance is considered.

Histamine receptor activation by unsaturated (allyl and propargyl) homologs of histamine

“…Cis-IAA can therefore be properly classified as a selective inhibitor of diamine oxidase. The apparent affinity of cis-IAA for DAO compares favorably with other inhibitors of this enzyme such as aminoguanidine which has an apparent affinity of 1.07 x 10-8 M [13].…”

“…1). The major emphasis of our experiments was focused on the pharmacodynamics of cis-IAA because preliminary data [11] showed that the cis-isomer had a relatively low Ki (1.7 x 10-7 M) for inhibition of DAO [13]. For comparison, the activity of the saturated homolog, imidazolylpropylamine Chemical structures of histamine and the histamine homologs.…”

Hypothesis: Etiologic and Molecular Mechanistic Leads for Sporadic Neurodegenerative Diseases Based on Experience With Western Pacific ALS/PDC

“…Additionally, N -methyl- N -formylhydrazine (MFH), which is produced during MMH metabolism, undergoes cytochrome P450-regulated oxidative metabolism and, via reactive nitrosamide intermediates, leads to the formation of DNA-damaging methyl free radicals (57). As with MAM and nitrosamines, the O 6 -methylation of guanine can cause liver and kidney lesions (58–63) and tumor formation (62). The risk of long-term adverse effects may be greater in individuals with genetic slow acetylation rates because decreased detoxication (acetylation) of MFH would result in larger amounts of MMH formed from gyromitrin (64, 65).…”

Gyromitra Mushrooms

“…It is found in rapidly proliferating tissues, such as intestinal mucosa and bone marrow. MFH noncompetitively inhibits diamine oxidase in vitro [25]. Inhibition of diamine oxidase can produce histamine concentrations that cause flushing, abdominal pain, nausea, vomiting, diarrhea, and headache.…”