L-(+)-(''S'')-Canavanine is a non-proteinogenic amino acid found in certain leguminous plants. It is structurally related to the proteinogenic α-amino acid L-

arginine Arginine is the amino acid with the formula (H2N)(HN)CN(H)(CH2)3CH(NH2)CO2H. The molecule features a guanidinium, guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) a ...

, the sole difference being the replacement of a methylene bridge ( unit) in arginine with an oxa group (i.e., an

oxygen Oxygen is a chemical element; it has chemical symbol, symbol O and atomic number 8. It is a member of the chalcogen group (periodic table), group in the periodic table, a highly reactivity (chemistry), reactive nonmetal (chemistry), non ...

atom) in canavanine. Canavanine is accumulated primarily in the

seed In botany, a seed is a plant structure containing an embryo and stored nutrients in a protective coat called a ''testa''. More generally, the term "seed" means anything that can be Sowing, sown, which may include seed and husk or tuber. Seeds ...

s of the organisms which produce it, where it serves both as a highly deleterious defensive compound against herbivores (due to cells mistaking it for arginine) and a vital source of

nitrogen Nitrogen is a chemical element; it has Symbol (chemistry), symbol N and atomic number 7. Nitrogen is a Nonmetal (chemistry), nonmetal and the lightest member of pnictogen, group 15 of the periodic table, often called the Pnictogen, pnictogens. ...

for the growing embryo. The related L- canaline is similar to

ornithine Ornithine is a non-proteinogenic α-amino acid that plays a role in the urea cycle. It is not incorporated into proteins during translation. Ornithine is abnormally accumulated in the body in ornithine transcarbamylase deficiency, a disorder of th ...

Toxicity

The mechanism of canavanine's toxicity is that organisms that consume it typically mistakenly incorporate it into their own

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

s in place of L-arginine, thereby producing structurally aberrant proteins that may not function properly. Cleavage by arginase also produces canaline, a potent insecticide. The toxicity of canavanine may be enhanced under conditions of protein starvation, and canavanine toxicity, resulting from consumption of '' Hedysarum alpinum'' seeds with a concentration of 1.2% canavanine weight/weight, has been implicated in the death of a malnourished Christopher McCandless.Krakauer, J., et al. (2015). "Presence of l-canavanine in Hedysarum alpinum seeds and its potential role in the death of Christopher McCandless." Wilderness & Environmental Medicine. (McCandless was the subject of Jon Krakauer's book (and subsequent

movie A film, also known as a movie or motion picture, is a work of visual art that simulates experiences and otherwise communicates ideas, stories, perceptions, emotions, or atmosphere through the use of moving images that are generally, sinc ...

) ''Into the Wild''). Can-Arg

In mammals

NZB/W F1, NZB, and DBA/2 mice fed L-canavanine develop a syndrome similar to systemic lupus erythematosus, while BALB/c mice fed a steady diet of protein containing 1% canavanine showed no change in lifespan.

Alfalfa Alfalfa () (''Medicago sativa''), also called lucerne, is a perennial plant, perennial flowering plant in the legume family Fabaceae. It is cultivated as an important forage crop in many countries around the world. It is used for grazing, hay, ...

seeds and sprouts contain L-canavanine. The L-canavanine in alfalfa has been linked to lupus-like symptoms in primates, including humans, and other auto-immune diseases. Often stopping consumption reverses the problem.

Tolerance

Some specialized herbivores tolerate L-canavanine either because they metabolize it efficiently (cf. L-canaline) or avoid its incorporation into their own nascent proteins.

By metabolic detoxification

Herbivores may be able to metabolize canavanine efficiently. The beetle ''Caryedes brasiliensis'' is able to break canavanine down to canaline, then further detoxifies canaline by reductive deamination to form homoserine and ammonia. As a result, the beetle not only tolerates the chemical, but uses it as a source of nitrogen to synthesize its other amino acids to allow it to develop.

By selectivity

An example of this ability can be found in the larvae of the tobacco budworm '' Heliothis virescens'', which can tolerate large ( lethal concentration 50 or LC₅₀ 300 mM) amounts of dietary canavanine. These larvae fastidiously avoid incorporation of L-canavanine into their nascent proteins due to gastrointestinal expression of canavanine hydrolase, an enzyme that cleaves L-canavanine into L-homoserine and hydroxyguanidine, and L-arginine kinase, which phosphorylates L-canavanine. In contrast, larvae of the tobacco hornworm '' Manduca sexta'' can only tolerate tiny amounts (1.0 microgram per kilogram of fresh body weight) of dietary canavanine because their arginine- tRNA ligase has little, if any, discriminatory capacity. No one has examined experimentally the arginine-tRNA synthetase of these organisms. But comparative studies of the incorporation of radiolabeled L-arginine and L-canavanine have shown that in ''Manduca sexta'', the ratio of incorporation is about 3 to 1. '' Dioclea megacarpa'' seeds contain high levels of canavanine. The beetle '' Caryedes brasiliensis'' is able to tolerate this however as it has the most highly discriminatory arginine-tRNA ligase known (as of 1982). In this insect, the level of radiolabeled L-canavanine incorporated into newly synthesized proteins is barely measurable. Moreover, this beetle uses canavanine as a nitrogen source (see above).

References

Bibliography

* * * * and in particularly large amounts in '' Canavalia gladiata'' (sword bean). ** {{Non-proteinogenic amino acids ......... Alpha-Amino acids Toxic amino acids Non-proteinogenic amino acids Plant toxins Oxime ethers Chris McCandless