Hypoglycin

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Hypoglycin
Hypoglycin
Names
IUPAC name
(S)-2-Amino-3-((S)-2-methylenecyclopropyl)propanoic acid
Other names
Hypoglycin A; Hypoglycine; 2-Methylenecyclopropanylalanine
Identifiers
156-56-9 YesY
ChEMBL ChEMBL1615355 N
ChemSpider 9943349 YesY
Jmol-3D images Image
PubChem 11768666
Properties
C7H11NO2
Molar mass 141.17 g·mol−1
Melting point 282 °C (540 °F; 555 K)
Except where noted otherwise, data is given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
 N verify (what isYesY/N?)
Infobox references

Hypoglycin, or most commonly hypoglycin A, is a toxic molecule, and a naturally occurring amino acid derivative found in the unripened fruit of the Ackee tree (Blighia sapida). Hypoglycin is toxic if ingested and is the causative agent of Jamaican vomiting sickness.[1] It[contradictory] competitively binds to enzymes used in the catabolism of lysine and is the reason why it and its metabolite methylene cyclopropyl acetic acid (MCPA) are toxic.

History[edit]

The Ackee tree, and thus its fruit, originated in Africa and made its way to the Caribbean sometime in the 18th century by Captain Bligh,[2] though the exact date of transfer is unknown. Its primary consumption and the majority of deaths occur in Jamaica, where it is included in the national dish: Ackee with saltfish. The entirety of the unripe Ackee fruit is toxic and contains large amounts of hypoglycin. The fruit is safe to eat only when the fruit is allowed to fully open and expose the large black seeds while on the tree. The levels of the toxin decrease over time though from approximately 1000 ppm to around 0.1 ppm in the mature fruit.[3] The seeds also contain an alternate form of hypoglycin, Hypoglycin B, which can also cause Jamaican vomiting sickness. Due to the toxicity of the fruit, importation of it is banned in the United States.[2] Since 1980, 271 cases of Jamaican vomiting sickness have occurred in Jamaica alone, with occasional outbreaks happening in other parts of the world, such as Haiti where over 100 cases of illness were reported in late 2000.[3]

Toxicity[edit]

The molecule responsible for the toxicity of hypoglycin is actually a metabolite of hypoglycin, methylenecyclopropane acetyl (MCPA). MCPA can then react with two important cofactors for fatty acid oxidation, carnitine and coenzyme A, which both has the effects of reducing the levels of these in tissue, and, in the case of coenzyme A, blocking some CoA dehydrogenase enzymes which are required for gluconeogenesis.[3] 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 hemodialisis in the case of renal failure.[4]

Synthesis[edit]

In 1958, John Carbon, William Martin, and Leo Swett were the first to synthesize hypoglycin, in racemic form, starting from 2-bromopropene and ethyl diazoacetate to form the cyclopropane ring.[5]

An example of a synthesis pathway of hypoglycin A

See also[edit]

References[edit]

  1. ^ "Ackee Fruit Toxicity". Medscape. 
  2. ^ a b "Plant toxins, Ackee poisoning". Institute of Tropical Medicine Antwerp. 
  3. ^ a b c "THE ACKEE FRUIT (BLIGHIA SAPIDA) AND ITS ASSOCIATED TOXIC EFFECTS". University of British Columbia. 
  4. ^ "Hypoglycin". TOXNET. 
  5. ^ Carbon, J. A.;Martin, W. B.;Swett, L. R. (1958), "SYNTHESIS OF α-AMINO- METHYLENECYCLOPROPANEPROPIONIC ACID (HYPOGLYCIN A)", J. Am. Chem. Soc. 80: 1002–1002, doi:10.1021/ja01537a066