A Mechanism of l‐Canaline Toxicity

Abstract

L-Canaline, a highly toxic structural analogue of l-ornithine, reacted with pyridoxal phosphate to form a stable, ninhydrin-positive complex. NMR analysis revealed the involvement of a Schiff's base in complex formation. Interaction of l-canaline with l-tyrosine decarboxylase, a known B₆-containing enzyme, curtailed significantly enzyme-mediated decarboxylation. Spectral scans provided evidence that the loss in catalytic activity is associated with the reaction of canaline with the pyridoxal phosphate moiety of the enzyme. Thus, the marked antimetabolic properties of canaline are due in part to its ability to form a Schiff's-base-containing complex with the B₆ moiety of the enzyme.