Methylene cyclopropyl acetic acid (MCPA) is found in lychee seeds and also a toxic metabolite in mammalian digestion after ingestion of

hypoglycin Hypoglycin may refer to: * Hypoglycin A * Hypoglycin B Hypoglycin B is a naturally occurring organic compound in the species '' Blighia sapida''. It is particularly concentrated in the fruit of the plant especially in the seeds. Hypoglycin B is t ...

Overview

Methylene cyclopropyl acetic acid (MCPA) is a compound found in lychee ('' Litchi chinensis'') seeds.Gray DO, Fowde
L. alpha-(methylenecyclopropyl)glycine from litchi seeds.
Biochem J 1962;82:385–9. It is also a metabolite in mammalian digestion after ingestion of

, a rare and potentially toxic amino acid, chemically related to the common amino acid

lysine Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. It contains an α-amino group (which is in the protonated form under biological conditions), an α-carboxylic acid group (which is in the deprotonated −C ...

. Hypoglycin is found in the unripe ackee fruit in Africa. Dihydrosterculic acid is the major carbocyclic fatty acid in the seed oils of ''Litchi chinensis''. It is a cyclopropane fatty acid; these have been found in many plants of the order Malvales ( Malvaceae), in up to 60% of seed oil content, depending on the species but also in leaves, roots and shoots. They are accompanied by small amounts of their cyclopropanoid analogues, i.e. cyclopropyl acetic acid.

Pathophysiology of MCPA

MCPA forms non-metabolizable esters with

coenzyme A Coenzyme A (CoA, SHCoA, CoASH) is a coenzyme, notable for its role in the synthesis and oxidation of fatty acids, and the oxidation of pyruvate in the citric acid cycle. All genomes sequenced to date encode enzymes that use coenzyme A as a subs ...

(CoA) and

carnitine Carnitine is a quaternary ammonium compound involved in metabolism in most mammals, plants, and some bacteria. In support of energy metabolism, carnitine transports long-chain fatty acids into mitochondria to be oxidized for energy production, an ...

, causing a decrease in their bioavailability and concentration in bodily tissue. Both of these cofactors are necessary for the

β-oxidation In biochemistry and metabolism, beta-oxidation is the catabolic process by which fatty acid molecules are broken down in the cytosol in prokaryotes and in the mitochondria in eukaryotes to generate acetyl-CoA, which enters the citric acid cycle, ...

of fatty acids, which in turn is vital for

gluconeogenesis Gluconeogenesis (GNG) is a metabolic pathway that results in the generation of glucose from certain non-carbohydrate carbon substrates. It is a ubiquitous process, present in plants, animals, fungi, bacteria, and other microorganisms. In vertebrat ...

. MCPA also inhibits the dehydrogenation of a number of Acyl-CoA dehydrogenases. The inhibition of one in particular, butyryl CoA dehydrogenase (a

short-chain acyl-CoA dehydrogenase Short-chain acyl-CoA dehydrogenase (, butyryl-CoA dehydrogenase, butanoyl-CoA dehydrogenase, butyryl dehydrogenase, unsaturated acyl-CoA reductase, ethylene reductase, enoyl-coenzyme A reductase, unsaturated acyl coenzyme A reductase, butyryl coenz ...

), causes β-oxidation to cease before fully realized, which leads to a decrease in the production of NADH and

Acetyl-CoA Acetyl-CoA (acetyl coenzyme A) is a molecule that participates in many biochemical reactions in protein, carbohydrate and lipid metabolism. Its main function is to deliver the acetyl group to the citric acid cycle (Krebs cycle) to be oxidized for ...

. The cascading effect continues, as this decrease in concentration further inhibits gluconeogenesis.

Formation of MCPA after ingestion of hypoglycin A and its toxicity

MCPA formation as a toxic metabolite of hypoglycin A

Hypoglycin A is a water-soluble liver toxin, that upon ingestion, leads to hypoglycemia through the inhibition of gluconeogenesis, a metabolic pathway that leads to the generation of glucose from non-carbohydrate carbon sources (i.e.

glucogenic amino acid A glucogenic amino acid (or glucoplastic amino acid) is an amino acid that can be converted into glucose through gluconeogenesis. This is in contrast to the ketogenic amino acids, which are converted into ketone bodies. The production of glucos ...

lactate Lactate may refer to: * Lactation, the secretion of milk from the mammary glands * Lactate, the conjugate base of lactic acid Lactic acid is an organic acid. It has a molecular formula . It is white in the solid state and it is miscible with ...

, and glycerol). In addition, it also limits Acyl and carnitine cofactors, which are instrumental in the oxidation of large fatty acids. Hypoglycin A undergoes deamination, forming α-ketomethylene-cyclopropylpropionic acid (KMCPP), which then forms MCPA through

oxidative decarboxylation Oxidative decarboxylation is a decarboxylation reaction caused by oxidation. Most are accompanied by α- Ketoglutarate α- Decarboxylation caused by dehydrogenation of hydroxyl carboxylic acids such as carbonyl carboxylic acid, malic acid, isocitr ...

. Hypoglycin A (and

hypoglycin B Hypoglycin B is a naturally occurring organic compound in the species '' Blighia sapida''. It is particularly concentrated in the fruit of the plant especially in the seeds. Hypoglycin B is toxic if ingested and is one of the causative agents of ...

) is found in the ackee fruit, the national fruit of Jamaica, and, like ''Litchi chinensis'', is a member of the family

Sapindaceae The Sapindaceae are a family of flowering plants in the order Sapindales known as the soapberry family. It contains 138 genera and 1858 accepted species. Examples include horse chestnut, maples, ackee and lychee. The Sapindaceae occur in tempera ...

. The fruit is rich in fatty acids, zinc, protein, and vitamin A. In the fully ripened

arils An aril (pronounced ), also called an arillus, is a specialized outgrowth from a seed that partly or completely covers the seed. An arillode or false aril is sometimes distinguished: whereas an aril grows from the attachment point of the see ...

of the fruit, Hypoglycin A is present at only 0.1ppm, but in the unripened fruit it can exceed a concentration of 1000ppm. Ingestion of the unripened fruit containing such a concentrated dose causes what is known as

Jamaican vomiting sickness Jamaican vomiting sickness, also known as toxic hypoglycemic syndrome (THS), acute ackee fruit intoxication, or ackee poisoning, is an acute illness caused by the toxins hypoglycin A and hypoglycin B, which are present in fruit of the ackee tree ...

. Depending on the severity of the case, the symptoms range from headache, rapid heart beat and sweating to dehydration and low blood pressure stemming from intense vomiting, to delirium and coma, and finally seizures and death. The symptoms stemming from lychee poisoning are near identical, both being caused by MCPA, with lychee seeds also containing methylenecyclopropyl glycine (MCPG), a homologue of Hypoglycin A.

Recent poisonings

In 2014, numerous children died in Bihar (the largest producer of lychees in India) after consuming lychees. The vast majority of the fatalities were undernourished children, their preexisting low blood sugar detrimentally amplifying the effects. It is also possible that they ate unripe lyches.NDTV Food. �
The Poisonous Litchi: Here's How Toxins in the Fruit Killed Children in Bihar
�� NDTV Food, NDTV Food, 4 Feb. 2017.

References

{{authority control Acetic acids Cyclopropanes Vinylidene compounds