Toxic Fungi of Western North America
Gyromitrin is one of a group of protein-bound hydrazines, whose pre-toxins are found mostly in the genus Gyromitra. The principal pre-toxin is gyromitrin (N-methyl-N-formylhydrazone) that breaks down quickly in the stomach and duodenum to acetaldehyde and N-methyl-N-formylhydrazine. Hydroxylation of this compound forms monomethylhydrazine (MMH) and other hydrazines. The methyformyl-hydrazones of pentanal, hexanal and also 3-methyl-butanol are also present in Gyromitra esculenta and other toxic Gyromitra species.
Fig.8. Gyromitrin hydrolysis to monomethylhydrazine (MMH)
MMH has a very narrow range of toxicity, which may account for some of the marked variation in actual symptoms. In addition, there may be less toxicity in western forms, although this hypothesis is unproven. The French have reported decreased MMH in the Spring and also at higher elevations, the latter possibly due to enhanced ultraviolet light degradation. (137) Western Gyromitra species commonly occur in the Spring and usually at relatively high altitudes where ultraviolet light is increased. These conditions help explain the benign course of poisoning in the Western areas of the US as compared to the Mid-West, where poisonings have often been severe, even causing death. Comparison is difficult, however, since Gyromitras are infrequently collected in the West, appearing only slightly ahead of the highly edible morel in mountain areas. The US military first studied MMH at Wright-Patterson Air Force Base in Ohio, because this volatile compound had been used as rocket propellant. (138)
MMH interferes with the action of pyridoxal phosphate and others of the vitamin B6 group by inhibition of the enzyme pyridoxine kinase. Vitamin B6 is needed as a co-factor in many enzymatic processes and a lack of pyridoxine kinase results in a decrease of GABA (g-aminobutyric acid), an inhibitory neurotransmitter in the brain. GABA reduces electrical overload on cerebration by decreasing stray signals—what one might call “static”--which tend to overwhelm our thinking. To do without GABA in our brain cells has been likened to attempts to hear a whisper at a rock concert.
MMH also attacks the enzyme GAD (glutamic acid decarboxylase), which reduces the conversion of glutamic acid to glutamate. Glutamate is needed for the synthesis of GABA and, along with glutamic acid, acts as an excitatory neurotransmitter. The decrease of both cerebral GABA and of cerebral glutamate probably account for most of the CNS symptomatology. The gastrointestinal symptoms, methemoglobinemia, liver and kidney failure require other mechanisms and remain unexplained. Monomethylhydrazine induces fetal abnormalities in experimental animals. Gyromitra species and other ascomycetes should not be eaten during pregnancy, especially in the first 3 months.