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Hypoglycin A is a naturally occurring amino acid derivative found in the unripened fruit of the Ackee tree (Blighia sapida) and in the seeds of the box elder tree (Acer negundo). It is toxic if ingested, and is the causative agent of Jamaican vomiting sickness. A 2017 Lancet report established a link between the consumption of unripened lychees (containing hypoglycin A or methylenecyclopropylglycine (MCPG)) resulting in hypoglycaemia and death from acute toxic encephalopathy.

Safety
Hypoglycin A itself is a yellow solid at room temperature and is only harmful when ingested. As such, avoiding ingestion of sources for hypoglycin A will prevent any harm. The LD50 as tested on rats which were orally administered the chemical was 98 mg/kg and induced lacrimation, somnolence, and vomiting. In order to avoid accidental poisonings, it is advised to wait until the fruit has matured and opened, exposing the black seeds. This decreases the levels of toxin in the fruit by a factor of 10,000.

Toxicity
Hypoglycin A is a protoxin, meaning that the molecule is not toxic in itself but is broken down into toxic products when ingested. The branched-chain alpha-keto acid dehydrogenase complex, that normally converts leucine, isoleucine, or valine into acyl-CoA derivatives, converts Hypoglycin A into highly toxic MCPA-CoA. The FAD cofactor necessary for the beta oxidation of fatty acids associates with the alpha carbon of MCPA-CoA creating an irreversible complex that disables the enzyme. In addition, MCPA-CoA blocks some enzymes that are required for gluconeogenesis.

The reduction in gluconeogenesis and the reduction in fatty acid oxidation are thought to be the cause of most of the symptoms of Jamaican vomiting sickness. The blocking of fatty acid metabolism causes cells to start using glycogen for energy. Once glycogen is depleted, the body is unable to produce more, which leads to a severe case of hypoglycemia. These biochemical effects are detected by an excess of medium chain fatty acids in urine and acidosis. Key treatments are aimed at circumventing or counteracting the biochemical changes, and include IV fluids and glucose, and hemodialysis in the case of renal failure.

These interruptions of acyl-CoA dehydrogenases will lead to symptoms of vomiting after several hours. In severe cases, notably common in children and malnourished individuals, hypoglycin A poisoning can lead to seizures, coma, and eventually death.



Synthesis
In 1958, John Carbon, William Martin, and Leo Swett were the first to synthesize hypoglycin A, in racemic form, starting from 2-bromopropene and ethyl diazoacetate to form the cyclopropane ring.