L-CANALINE BASE

Description

L-Canaline is an aminooxy analog of ornithine that irreversibly inhibits aminotransferases (transaminases), including ornithine aminotransferase (K_i = 2 μM). It forms oximes with α-keto acids and aldehydes, most notably with pyridoxal phosphate, an essential cofactor of aminotransferases. L-Canaline is naturally found in plants, including legumes, and is involved in the metabolism of L-canavanine, an aminooxy analog of arginine. It is cytotoxic to a range of organisms, including bacteria, insects, and parasites.

Definition

ChEBI: L-canaline is a non-proteinogenic L-alpha-amino acid that is L-homoserine in which the hydroxy group at position 4 is substituted by an aminooxy group. It has been isolated from legumes and plays an essential role in lugume chemical defense against insects. It has a role as a plant metabolite, an antineoplastic agent, an antimetabolite and a phytogenic insecticide. It is functionally related to a L-homoserine. It is a tautomer of a L-canaline zwitterion.

Synthesis Reference(s)

Tetrahedron, 23, p. 4441, 1967 DOI: 10.1016/S0040-4020(01)88842-6

in vitro

canaline strongly inhibited the activity of pyridoxal-dependent enzymes, including amino acid decarboxylases, 5-hydroxytryptophan decarboxylase, aminotransferases, tyrosine aminotransferase, ornithine transcarbamylase and plasma diamino-oxidase. the canaline inhibition was due to complex formation between canaline and the pyridoxal coenzyme. l-canaline is one of the most potent inhibitors of pyridoxal enzymes. the ic50 value of l-canaline against ornithine aminotransferase was 3 ×10-6m [4].

in vivo

intraperitoneal administration of 500 mg of dl-canaline/kg body wt. only produced a transient inhibition of oat in brain and liver by 65-70%, suggesting that dl-canaline was not a useful tool in studies of biological consequences of oat inhibition. [1].

References

[1] bolkenius f n, kndgen b, seiler n. dl-canaline and 5-fluoromethylornithine. comparison of two inactivators of ornithine aminotransferase[j]. biochemical journal, 1990, 268(2): 409-414.
[2] rosenthal g a, rhodes d. l-canavanine transport and utilization in developing jack bean, canavalia ensiformis (l.) dc.[leguminosae][j]. plant physiology, 1984, 76(2): 541-544.
[3] peraino c, bunville l g, tahmisian t n. chemical, physical, and morphological properties of ornithine aminotransferase from rat liver[j]. journal of biological chemistry, 1969, 244(9): 2241-2249.
[4] rahiala e l, kekomki m, jnne j, et al. inhibition of pyridoxal enzymes by l-canaline[j]. biochimica et biophysica acta (bba)-enzymology, 1971, 227(2): 337-343.