We have all heard about deadly foods, deadly mushrooms in particular, but it is rare to discover that a mushroom that people have been eating for a while is the responsible agent for sudden deaths of perfectly healthy people, with not too many obvious symptoms. the case of Yunnan sudden unexplained death syndrome has now been solved. It is caused by the mushroom Trogia venenata. The deaths followed a funny pattern, they occurred only in a narrow altitude band in the hills of Yunnan and neighboring provinces, in Southwest China, and only during the rainy summer season. The chinese Center for Disease Control and Prevention had suspected the innocent looking white mushroom since 2009, and when they told people to stop eating it, the syndrome disappeared. But what was the deadly toxin and how did it cause the sudden death? It turns out that T. venenata produced 2 novel forms of unsaturated amino acids, and also γ-guanidinobutyric acid, a compound known to cause seizures in lab rats. Using mice to determine the cause of death, researchers found that the mushroom causes extreme hypoglycemia, in other words, blood sugar drops to such low levels, that cells cannot function anymore. At the molecular level, the toxins act in a manner similar to hypoglycin, the deadly compound found in unripe ackee fruit and seeds, which cause Jamaican vomiting sickness, with seizures and sometimes death. Hypoglycin blocks beta-oxidation, which is the production of ATP, the "currency unit" for energy transfer in cells, from fatty acids, that regenerates glucose. Since the heart is very dependent on beta-oxidation, this would explain the sudden deaths. The weird fungal compounds look structural similar to hypoglycin, hence, the victims do not simply become hypoglycemic and faint or seizure, because in addition to brain effects, their heart stops from blocked beta-oxidation. Case closed, although further toxicology tests will be carried out to study possible synergistic or dose effects, since some people who have eaten the mushroom have not died or even gotten ill.
BEIJING—Southwest China's hill country has long been stalked by a killer whose victims sometimes drop dead in midsentence. Two years ago, researchers unmasked the likely villain as a mushroom, new to science, which no one had realized is poisonous. Now they have isolated its toxins and propose an astonishing modus operandi.
Over the past few decades, health authorities in China have blamed more than 400 deaths on Yunnan sudden unexplained death. The syndrome exhibits a curious pattern. It strikes almost exclusively during the summer rainy season in highland villages in a narrow altitude band in Yunnan and possibly neighboring provinces. In 2010, an investigation spearheaded by epidemiologist Zeng Guang of the Chinese Center for Disease Control and Prevention (CDC) in Beijing identified the culprit as a small white mushroom (Science, 9 July 2010, p. 132), since named Trogia venenata.
In the latest work, Liu Jikai, a medicinal chemist at Kunming Institute of Botany, and Chinese CDC colleagues set out to pin-point the poisons. After months of pains-taking effort, Liu says, “we isolated almost every unusual compound” in the mushroom. Three were toxic: two novel unsaturated amino acids* and γ-guanidinobutyric acid, a compound normally found in the brain that induces seizures in lab animals. Unlike virtually all known natural amino acids, which have left-handed chirality, the Trogia pair is right-handed. Unsaturated amino acids are known toxins in other poisonous mushrooms, says Kimiko Hashimoto, an organic chemist at Kyoto Pharmaceutical University in Japan who with colleagues isolated a vicious muscle-melting toxin from Russula subnigricans, a mushroom found in Asia and North America. Puzzlingly, however, T. venenata's toxins are not particularly potent. “The toxicities of the newly isolated amino acids are rather weak,” Hashimoto says.
Also contrary to expectations, the Trogia toxins had only a mild effect on the heart. Mice fed an extract from the mushroom died. But the enzyme creatine kinase, a marker for heart attacks and other manifestations of muscle damage, was only slightly elevated in mouse blood—certainly not high enough to explain the toxins' lethality. Drilling deeper into the toxicology data, the team discovered that their mice had extremely low blood sugar. The “profound hypoglycemia” triggered by the mushroom extract “may explain the fatal outcome in humans and experimental animals,” Liu and colleagues report in the 5 March issue of Angewandte Chemie.
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Here's my ignorant-question-of-the-day: do these (and other toxic) mushrooms seem to go out of their way to produce these unsaturated amino acids or do these just occur accidentally from normal day-to-day (so to speak =) mushroom maintenance?
Not an ignorant question at all. Most plants produce toxins as a defense against being eaten, or as a defense against parasites or microbes. Fungi do this, too. Fungus produce antibiotics, also, to defend themselves (not us, LOL) against being colonized by bacteria. Some unsaturated amino acids, and some gamma-butyric acids, too, have a potent antimicrobial activity, they are called lantibiotics. The biochemistry of fungal cells make it easy for them to produce these compounds.
What is meant by "unsaturated amino acids" ?
First time that I have come across this expression so please pardon my ignorance?
LOL! I'm as ignorant as you =)
Here's my guess, an amino acid that is not complete in one way or another and remains susceptible to be more interactive again, in one way or another. Can I be vaguer, Prof A.?
LOL! in a way, it is "not complete", meaning it does not have all the hydrogen molecules it could have, if it didn't have the carbon-carbon double bond (see below).
"Unsaturated" in organic chemistry means having carbon carbon double bonds. The number of C-C double bonds correlates with the number of hydrogen atoms, inversely. The more C-C double bonds, the less hydrogen molecules. You maybe familiar with the term "unsaturated" in the context of fatty acids, but the term applies to any compound with C-C double bonds in organic chemistry. "Unsaturated amino acids" is not a common expression, at all. The 20 amino acids that are the protein building blocks are not unsaturated. The do not have any C-C double bonds. They are represented as C=C in the formulas, or simply "=" (the carbon does not need to be written).
Thank you for the enlightenment.
So saturated - -fatty acids, or -Amino Acids contain no C=C bonds then?
Correct. Here's a little bit more detail about unsaturated vs saturated compounds.