Mechanism of Action of β-N-Oxalyl-L-α,β-diaminopropionic Acid, Lathyrus sativus Neurotoxin: Effect on Brain Lysosomes

Abstract

β-N-Oxalyl-L-α,β-diaminopropionic acid (ODAP), the toxic amino-acid isolated from the seeds of Lathyrus sativus^1,2, has been implicated in human neurolathyrism, a crippling disease found in central India and attributed to the consumption of this vetch³. ODAP causes convulsions in young animals when injected intraperitoneally^4,5. The toxin induces hind leg paralysis in monkeys when introduced into the immediate environment of the brain through the lumbar route⁶. ODAP is a potent excitant amino-acid in the Betz cells of cat spinal cord⁷ and produces biochemical changes in the rat brain typical of an excitant amino-acid⁸. Chronic ammonia toxicity has been implicated in the mode of action of ODAP, leading to convulsions in young rats⁹. Protein degradation in the brain may be an early event in ODAP-induced convulsions¹⁰. Nucleotides have also been found to accumulate in the brain of young rats injected with ODAP (our unpublished data). Thus, a generalized increase in the catabolism of protein and nucleic acids in ODAP induced convulsions has been indicated by earlier investigations. We have examined the effect of ODAP on chick brain lysosomes possibly leading to a liberation of acid hydrolases.