Effects of quaternary ammonium compounds on the degradation of lipids in lysosomes.

We have examined effects of quaternary ammonium compounds on the in vitro degradation of endogenous lipids in isolated lysosomes. The degree of lipid degradation was assessed by determining hydrolysis products of labeled lipid. Lipolysis was inhibited by quaternary ammonium compounds. The degrees of inhibition were as follows: ethidium bromide greater than N-methylatropinium bromide (NMA) greater than tubocurarine. The inhibition of lipolysis by these quaternary ammonium compounds is not necessarily correlated with the differences in their polarities, molecular weight or structures. The degradation of three phospholipid classes was inhibited by NMA with phosphatidylcholine the most vulnerable. The effect of NMA on the hydrolysis of [14C]dipalmitoylphosphatidylcholine (phospholipid) by lysosomal soluble proteins was also examined. The effect of NMA on phospholipase A1 was assessed by the formation of lysophosphatidylcholine, and that on phospholipase C was assessed as the sum of mono- and diglyceride formations. The action of NMA on the phospholipid degradation was similar to that of cationic amphiphilic drugs, but it differed somewhat from that of chloroquine for each enzyme. From these results, it was concluded that one of the inhibitory mechanisms of phospholipid degradation by NMA was the direct interaction between NMA and phospholipase A1 or C.