L---Canavanine is a non-proteinogenic amino acid found in certain leguminous plants. It is structurally related to the proteinogenicα-amino acid L-arginine, the sole difference being the replacement of a methylene bridge in arginine with an oxa group in canavanine. Canavanine is accumulated primarily in the seeds of the organisms which produce it, where it serves both as a highly deleterious defensive compound against herbivores and a vitalsource of nitrogen for the growing embryo. The mechanism of canavanine's toxicity is that organisms that consume it typically mistakenly incorporate it into their own proteins in place of L-arginine, thereby producing structurally aberrant proteins that may not function properly. The toxicity of canavanine may be enhanced under conditions of protein starvation, and canavanine toxicity resulting from consumption of Hedysarum alpinum seeds, which contain quantities of canavanine around 1%, has been implicated in the death of Christopher McCandless.. Some specialized herbivores tolerate L-canavanine either because they metabolize it efficiently or avoid its incorporation into their own nascent proteins. An example of this ability can be found in the larvae of the tobacco budwormHeliothisvirescens, which can tolerate massive amounts of dietary canavanine. These larvae fastidiously avoid incorporation of L-canavanine into their nascent proteins. In contrast, larvae of the tobacco hornwormManducasexta can only tolerate tiny amounts 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. Diocleamegacarpa seeds contain high levels of canavanine. The beetle Caryedesbrasiliensis is able to tolerate this however as it has the most highly discriminatory arginine-tRNA ligase known. 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 to synthesize its other amino acids to allow it to develop. 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 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.
