Graham D G, Abou-Donia M B
J Toxicol Environ Health. 1980 May;6(3):621-31. doi: 10.1080/15287398009529880.
Inhibition of the sulfhydryl enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) by 2,5-hexanedione (2,5-HD) was found to be 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 10(4) 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, on the othe hand, 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.
已发现2,5 -己二酮（2,5 - HD）对巯基酶甘油醛 - 3 -磷酸脱氢酶（GAPDH）的抑制作用是不可逆的，该过程通过一个可逆的酶 - 抑制剂中间体进行，而丙酮是一种弱可逆抑制剂。将2,5 - HD和丙酮与对氯汞苯甲酸（PCMB）和N - 乙基马来酰亚胺（NEM）进行比较表明，前者并非重要的巯基试剂，因为它们必须以比PCMB或NEM高10⁴倍以上的浓度存在才能对该酶产生可测量的抑制作用。因此，2,5 - HD对GAPDH的抑制作用在己烷神经病变的分子发病机制中不太可能具有任何意义。另一方面，2,5 - HD抑制作用的不可逆性表明，2,5 - HD与蛋白质上的氨基而非巯基发生反应。这种反应被认为是己烷神经病变中的分子损伤。
