Inhibition of sterologenesis but not glycolysis in 2,5-hexanedione-induced distal axonopathy in the rat

If glycolysis is inhibited in distal axonopathy, there should be a concomitant inhibition of lipogenesis from glucose. To investigate this possibility, lipogenesis from [¹⁴C]glucose and [³H]acetate was studied in sciatic nerves incubated with iodoacetate, a known inhibitor of glycolysis, in sciatic nerves incubated with 2,5-hexanedione, a putative inhibitor of glycolysis, and in sciatic nerves from rats exhibiting clinical signs of peripheral neuropathy induced by 2,5-hexanedione. Nerves incubated with 1.0 mm iodoacetate, in comparison with untreated nerves, exhibited decreased incorporation of [¹⁴C]glucose into sterols + diacylglycerols (33-fold), free fatty acids (14-fold), triacylglycerols (27-fold), and phospholipids (21-fold). In addition, these nerves exhibited decreased incorporation of [³H]acetate into sterols + diacylglycerols (30-fold), free fatty acids (2-fold), triacylglycerols (23-fold), and phospholipids (12-fold). In contrast, the incorporation of [¹⁴C]glucose into sterols + diacylglycerols, free fatty acids, and triacylglycerols was not affected by 1.0 mm 2,5-hexanedione. Compared to untreated nerves, nerves incubated with 1.0 mm 2,5-hexanedione exhibited a small decrease (15%) in the incorporation of [¹⁴C]glucose into phospholipids. Nerves from rats given 1% 2,5-hexanedione in the drinking water for 6 weeks, in comparison with those from pair-fed control rats, exhibited decreased (45%) incorporation of [¹⁴C]glucose and [³H]acetate into digitonin-precipitable sterols. Nerves from 2,5-hexanedione-treated and pair-fed control rats exhibited similar incorporation of [¹⁴C]glucose and [³C]acetate into free fatty acids, triacylglycerols, and phospholipids. The data indicate that while sterologenesis is inhibited in distal axonopathy, glycolysis is not.