Methylene cyclopropyl acetic acid (MCPA) is found in

lychee Lychee ( , ; ''Litchi chinensis''; ) is a monotypic taxon and the sole member in the genus ''Litchi'' in the soapberry family, Sapindaceae. There are three distinct subspecies of lychee. The most common is the Indochinese lychee found in So ...

seeds and is also a toxic

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

in mammalian digestion after eating hypoglycin, present in the unripe

ackee The ackee (''Blighia sapida''), also known as acki, akee, or ackee apple, is a fruit of the Sapindaceae ( soapberry) family, as are the lychee and the longan. It is native to tropical West Africa. The scientific name honours Captain William B ...

fruit, grown in Jamaica and in Africa. By blocking

coenzyme A Coenzyme A (CoA, SHCoA, CoASH) is a coenzyme, notable for its role in the Fatty acid metabolism#Synthesis, synthesis and Fatty acid metabolism#.CE.B2-Oxidation, oxidation of fatty acids, and the oxidation of pyruvic acid, pyruvate in the citric ac ...

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 from the cytosol into mitochondria to be oxidized for f ...

, MPCA causes a decrease in

β-oxidation In biochemistry and metabolism, beta oxidation (also β-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. Acetyl-CoA enters ...

fatty acids In chemistry, in particular in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, ...

, and hence

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

Overview

Methylene cyclopropyl acetic acid (MCPA) is a compound found in lychee (''

Litchi chinensis Lychee ( , ; ''Litchi chinensis''; ) is a monotypic taxon and the sole member in the genus ''Litchi'' in the Sapindus, soapberry family, Sapindaceae. There are three distinct subspecies of lychee. The most common is the Indochinese lychee fo ...

'') seeds.Gray DO, Fowde
L. alpha-(methylenecyclopropyl)glycine from litchi seeds.
Biochem J 1962;82:385–9. The major carbocyclic fatty acid in the seed oils of ''Litchi chinensis'' is a cyclopropane fatty acid named Dihydrosterculic acid; these have been found in many plants of the order

Malvales The Malvales are an Order (biology), order of flowering plants. As circumscribed by Angiosperm Phylogeny Group, APG II-system, the order includes about 6000 species within nine Family (biology), families. The order is placed in the eurosids II, w ...

(

Malvaceae Malvaceae (), or the mallows, is a family of flowering plants estimated to contain 244 genera with 4225 known species. Well-known members of economic importance include Theobroma cacao, cacao, Cola (plant), cola, cotton, okra, Hibiscus sabdariffa, ...

), 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. MPCA is also a

in mammalian digestion after ingestion of hypoglycin, a rare and potentially toxic

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

, 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. Lysine contains an α-amino group (which is in the protonated form when the lysine is dissolved in water at physiological pH), an α-carboxylic acid group ( ...

. Hypoglycin is found in the unripe

fruit.

Pathophysiology

MCPA forms non-metabolizable

esters In chemistry, an ester is a chemical compound, compound derived from an acid (either organic or inorganic) in which the hydrogen atom (H) of at least one acidic hydroxyl group () of that acid is replaced by an organyl group (R). These compounds c ...

with

(CoA) and

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

, which in turn is vital for

. MCPA also inhibits the

dehydrogenation In chemistry, dehydrogenation is a chemical reaction that involves the removal of hydrogen, usually from an organic molecule. It is the reverse of hydrogenation. Dehydrogenation is important, both as a useful reaction and a serious problem. At ...

of a number of Acyl-CoA dehydrogenases. The inhibition of one in particular, butyryl CoA dehydrogenase (a short-chain acyl-CoA dehydrogenase), causes β-oxidation to cease before fully realized, which leads to a decrease in the production of

NADH Nicotinamide adenine dinucleotide (NAD) is a coenzyme central to metabolism. Found in all living cells, NAD is called a dinucleotide because it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an ade ...

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 oxidation, o ...

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

Formation after ingestion of hypoglycin A

MCPA formation as a toxic metabolite of hypoglycin A

Hypoglycin A is a water-soluble liver toxin, that upon ingestion, leads to

hypoglycemia Hypoglycemia (American English), also spelled hypoglycaemia or hypoglycæmia (British English), sometimes called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's tria ...

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 glucose ...

s, lactate, and

glycerol Glycerol () is a simple triol compound. It is a colorless, odorless, sweet-tasting, viscous liquid. The glycerol backbone is found in lipids known as glycerides. It is also widely used as a sweetener in the food industry and as a humectant in pha ...

). In addition, it also limits Acyl and carnitine cofactors, which are instrumental in the oxidation of large fatty acids. Hypoglycin A undergoes

deamination Deamination is the removal of an amino group from a molecule. Enzymes that catalysis, catalyse this reaction are called deaminases. In the human body, deamination takes place primarily in the liver; however, it can also occur in the kidney. In s ...

, forming α-ketomethylene-cyclopropylpropionic acid (KMCPP), which then forms MCPA through oxidative decarboxylation. Hypoglycin A (and hypoglycin B) is found in the

fruit, the national fruit of Jamaica, and, like ''Litchi chinensis'', is a member of the family

Sapindaceae The Sapindaceae are a family (biology), family of flowering plants in the order Sapindales known as the soapberry family. It contains 138 genera and 1,858 accepted species. Examples include Aesculus, horse chestnut, maples, ackee and lychee. The ...

. The fruit is rich in fatty acids, zinc, protein, and vitamin A. In the fully ripened arils of the fruit, Hypoglycin A is present at only 0.1ppm, but in the unripened fruit it can exceed a concentration of 1000ppm.

Toxicity

Ingestion of the unripened fruit containing such a concentrated dose causes what is known as Jamaican vomiting sickness. 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 nearly 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 Bihar ( ) is a states and union territories of India, state in Eastern India. It is the list of states and union territories of India by population, second largest state by population, the List of states and union territories of India by are ...

(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 lychees.NDTV Food. �
The Poisonous Litchi: Here's How Toxins in the Fruit Killed Children in Bihar
�� NDTV Food, NDTV Food, 4 Feb. 2017. An earlier poisoning incident occurring in 2011 -also in Bihar- has been recorded. Fourteen children reportedly perished in this incident.

References

{{authority control Acetic acids Cyclopropanes Vinylidene compounds Plant toxins Sapindaceae