Action of β‐N‐Oxalylamino‐l‐Alanine on Mouse Brain NADH‐Dehydrogenase Activity

doi:10.1046/j.1471-4159.1995.65041842.x

Paper

Action of β‐N‐Oxalylamino‐l‐Alanine on Mouse Brain NADH‐Dehydrogenase Activity

Published Oct 1, 1995 · M. Sabri, B. Lystrup, D. Roy

Journal of Neurochemistry

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17

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0

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Abstract

Abstract: β‐N‐Oxalylamino‐l‐alanine (l‐BOAA), a non‐protein neuroexcitatory amino acid present in the seeds of Lathyrus sativus (chickling or grass pea), is known to produce its neurotoxic effects by overstimulation of non‐N‐methyl‐d‐aspartate receptors, especially α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid (AMPA) receptors, at micromolar concentrations. It has recently been reported that l‐BOAA selectively inhibits mitochondrial enzyme NADH‐dehydrogenase (NADH‐DH) in brain slices at subpicomolar concentrations. The present study finds that up to 4 mM concentrations of pure l‐BOAA fail to inhibit NADH‐DH activity in mouse brain homogenate and isolated brain mitochondria. Two known inhibitors (rotenone and 1‐methyl‐4‐phenylpyridinium ion, MPP+) of this mitochondrial enzyme produced significant inhibition under identical conditions. NADH‐DH inhibition was also not observed in the homogenate or mitochondria from the brains of animals systemically treated with convulsive doses of l‐BOAA. Some inhibition (20–37%) of NADH‐DH activity was observed in mouse brain slices incubated with 100–1,000 µM concentrations of l‐BOAA for 1 h at 37°C in an atmosphere of 95% O2 and 5% CO2, but the inhibition was nonselective, because the activity of another mitochondrial enzyme, succinic dehydrogenase, was similarly inhibited by l‐BOAA. These results are in contrast with the report that l‐BOAA inhibits mitochondrial NADH‐DH selectively at subpicomolar concentrations. We suggest the observed nonselective NADH‐DH inhibition in mouse brain slices treated with l‐BOAA is caused by neuronal damage through an excitotoxic mechanism.

In Vitro Study

Study Snapshot

L-BOAA, found in chickling or grass pea seeds, fails to selectively inhibit NADH-DH activity in mouse brain slices, suggesting neuronal damage through an excitotoxic mechanism.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

Paper

Action of β‐N‐Oxalylamino‐l‐Alanine on Mouse Brain NADH‐Dehydrogenase Activity

References

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L-BOAA, a plant toxin found in Lathyrus sativus, selectively inhibits brain mitochondrial enzyme NADH-dehydrogenase, leading to neurological disorders like Lathyrism, and its protective effect can be blocked by mitochondrial glutathione.

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MPP+ impairs oxidative phosphorylation in rat striatum, leading to excitotoxic neuronal degeneration and slow neurodegenerative diseases.

Citations

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Dietary dependence on grass pea and cassava roots may cause neurodegenerative disorders like lathyrism and konzo, with potential health risks from cyanide and other cyanogenic plants.

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The neurotoxicity of l-ODAP may be due to interference in tyrosine metabolism, potentially explaining species differences in susceptibility to this neurotoxin.

Toxic models of upper motor neuron disease

Neurotoxic disorders (neuro)lathyrism and neurocassavism are self-limiting disorders primarily targeting the Betz cell, with both disorders resulting in spastic paraparesis.