Studies of the molecular pathogenesis of hexane neuropathy. I. Evaluation of the inhibition of glyceraldehyde‐3‐phosphate dehydrogenase by 2,5‐hexanedione

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Abstract
Inhibition of the rabbit muscle sulfhydryl enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) by 2,5-hexanedione (2,5-HD) was irreversible, proceeding via a reversible enzyme-inhibitor intermediate, while acetone was a weak reversible inhibitor. Comparison of 2,5-HD and acetone with p-chloromercuribenzoate (PCMB) and N-ethylmaleimide (NEM) demonstrated that the former are not significant sulfhydryl reagents, since they must be present at more than 104 times higher concentrations than PCMB or NEM to effect measurable inhibition of this enzyme. Thus it is unlikely that inhibition of GAPDH by 2,5-HD has any significance in the molecular pathogenesis of hexane neuropathy. The irreversibility of 2,5-HD inhibition suggests that 2,5-HD reacts with amino groups rather than sulfhydryl groups on proteins. This reaction is proposed as the molecular lesion in hexane neuropathy.