PHENYTOIN INCREASES SPECIFIC TRIACYLGLYCEROL FATTY ESTERS IN SKELETAL-MUSCLE FROM HORSES WITH HYPERKALEMIC PERIODIC PARALYSIS

Previous studies have demonstrated that phenytoin decreases the levels of triacylglycerols in several tissues other than skeletal muscle. Si nce phenytoin is clinically effective in several skeletal muscle disor ders, triacyiglycerol metabolism in skeletal muscle from four normal Q uarter horses and four Quarter horses with hyperkalemic periodic paral ysis was examined. The horses with hyperkalemic periodic paralysis had low levels of 18:3 in the phospholipids, low levels of 16:0, 16:1 and 18:3 in the free fatty acids and low levels of 20:4 in triacylglycero ls. Triacylglycerol levels were increased in skeletal muscle from seve n (three controls, four hyperkalemic periodic paralysis) of the eight horses on treatment with oral phenytoin for one week. Instead of an in crease in all fatty ester types only 16:0, 16:1, 18:1 and 18:2 were si gnificantly increased. Total lipid phosphorus and the distributions of phospholipid fatty esters and free fatty acids were not significantly altered by phenytoin treatment in most cases. An alteration in triacy lglycerol metabolism by phenytoin was also observed in primary culture s of normal equine skeletal muscle radiolabeled with 18:1, but not in those radiolabeled with 18:2. These findings suggest that phenytoin do es not just increase the levels of triacylglycerol in skeletal muscle, but alters the utilization and incorporation of fatty esters. These f indings suggest a potential involvement of triacylglycerol metabolism in the clinical efficacy of phenytoin in hyperkalemic periodic paralys is.