Studies of the molecular pathogenesis of hexane neuropathy

The observations suggest that the sequence of events in the crosslinking of neurofilaments during chronic n -hexane intoxication may be metabolism to 2,5-hexanedione, formation of an imine with lysyl residues, cyclization to form a pyrrole, autoxidation of the pyr role, and finally covalentCrosslinking involving pyr Role rings.

Abstract

In the reaction between ethanolamine and 2,5-hexanedione, 1-(2-hydroxyethyl)-2,5-dimethylpyrrole was formed, and the pyrrole was found to autoxidize to form an orange chromophore. Similar orange chromophores were observed in the reaction of 2,5-hexanedione, 2,5-heptanedione, and 3,6-octanedione with a variety of primary amines and with proteins. The development of the orange chromophore in the reaction of 2,5-hexanedione with proteins was attended by a proportional derivatization of lysyl residues and by extensive intramolecular and intermolecular crosslinking. These observations suggest that the sequence of events in the crosslinking of neurofilaments during chronic n-hexane intoxication may be metabolism to 2,5-hexanedione, formation of an imine with lysyl residues, cyclization to form a pyrrole, autoxidation of the pyrrole, and finally covalent crosslinking involving pyrrole rings.