Gyromitra Mushroom Toxicity

Biotransformation reactions in the liver are classified as either phase I or II reactions. Phase I reactions involve the loss or gain of biological activity by hydrolysis or redox reactions. Rarely, substances may retain their bioactivity after undergoing a phase I reaction. Meanwhile, phase II reactions bind a functional group to the substance being metabolized by a process known as conjugation. Phase II substrates may either be the parent compound or a phase I derivative of this compound. The liver's functional groups for conjugation include endogenous glucuronic acid, sulfate, acetate, glutathione, and amino acids. Phase I enzyme systems are found mainly in the endoplasmic reticulum. In contrast, phase II enzymes are chiefly cytosolic. Cytochrome P450 isoforms carry out these biotransformation reactions. Some central nervous system (CNS) neurotransmitters are amino acids. The inhibitory neurotransmitter ϒ-aminobutyric acid (GABA) is an example. GABA receptors are ubiquitous in the brain and presynaptic spinal cord neurons, reflecting their important role as neuronal firing regulators.  GABA receptors are divided into types A, B, and C. GABAA receptors are ligand-gated chloride ion channels and are the most abundant. These receptors are the common targets of antiepileptic drugs, including barbiturates and benzodiazepines. GABAB receptors are G-protein-coupled receptors that inhibit adenylyl cyclase, activate potassium channels, and decrease calcium conductance. Presynaptic GABAB receptors act as autoreceptors that inhibit GABA release. GABAC receptors are transmitter-gated chloride channels and are the least abundant. GABA is much more potent at GABAC than GABAA receptors. Mushrooms are the spore-producing fruiting bodies of the kingdom Fungi, with approximately 135,000 species. Of the approximately 5,000 mushroom species hunted by foragers worldwide, only 2% are poisonous to humans. One of these poisonous mushrooms, , also known as the false morel, has a unique toxicity profile. The mushroom derives its name, " from the Latin word for "edible." Certain cultures consider this mushroom safe to eat, provided that proper preparation techniques, such as parboiling, are used to reduce its toxicity. Unfortunately, several poisoning incidences have been reported in foragers seeking and ingesting this mushroom speciesmorphologically resembles true morels belonging to the  species and can thus be confused with this nonpoisonous mushroom (see . ). The  syndrome consists of a gastrointestinal prodrome occurring more than 5 hours after eating . Acute liver injury can occur over the next 2 days. Acute kidney injury may occur to a lesser degree. Confusion characterizes acute CNS toxicity in many instances. However, refractory seizures may occur in the most severe cases. The substance responsible for poisoning is the toxic metabolite monomethylhydrazine (MMH) derived from gyromitrin produced by this mushroom. MMH binds to and inhibits pyridoxal phosphokinase, which activates pyridoxal 5-phosphate, the key cofactor in GABA synthesis. Subsequent GABA depletion leads to CNS excitation and seizures. MMH is also hepatotoxic and nephrotoxic.