PMID: 9166742Jun 1, 1997Paper

Inhibition of tyrosine aminotransferase by beta-N-oxalyl-L-alpha,beta-diaminopropionic acid, the Lathyrus sativus neurotoxin

Journal of Neurochemistry
K Shasi VardhanS L N Rao

Abstract

Species differences in susceptibility are a unique feature associated with the neurotoxicity of beta-N-oxalyl-L-alpha,beta-diaminopropionic acid (L-ODAP), the Lathyrus sativus neurotoxin, and the excitotoxic mechanism proposed for its mechanism of toxicity does not account for this feature. The present study examines whether neurotoxicity of L-ODAP is the result of an interference in the metabolism of any amino acid and if it could form the basis to explain the species differences in susceptibility. Thus, Wistar rats and BALB/c (white) mice, which are normally resistant to L-ODAP, became susceptible to it following pretreatment with tyrosine (or phenylalanine), exhibiting typical neurotoxic symptoms. C57BL/6J (black) mice were, however, normally susceptible to L-ODAP without any pretreatment with tyrosine. Among the various enzymes associated with tyrosine metabolism examined, the activity of only tyrosine aminotransferase (TAT) was inhibited specifically by L-ODAP. The inhibition was noncompetitive with respect to tyrosine (Ki = 2.0 +/- 0.1 mM) and uncompetitive with respect to alpha-ketoglutarate (Ki = 8.4 +/- 1.5 mM). The inhibition of TAT was also reflected in a marked decrease in the rate of oxidation of tyrosine by liver ...Continue Reading

Citations

Aug 19, 2009·Metabolic Brain Disease·Angela M SgaravattiCarlos Severo Dutra-Filho
Aug 30, 2000·Toxicology in Vitro : an International Journal Published in Association with BIBRA·R GriffithsC Meredith
Feb 5, 2010·Cell Calcium·Marijke Van MoorhemLuc Leybaert

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