Effects of phospholipids on sphingomyelin hydrolysis induced by intestinalalkaline sphingomyelinase: An in vitro study

Digestion of dietary sphingomyelin (SM) is catalyzed by intestinal alkaline sphingomyelintase (SMase) and may have important implications in colonic t umorigenesis. Previous studies demonstrated that digestion and absorption o f dietary SM was slow and incomplete and that the colon was exposed to SM a nd its hydrolytic products including ceramide. In the present work, we stud ied the influences of glycerophospholipids and hydrolytic products of phosp hatidylcholine (PC: i.e., lyso-PC, fatty acid, diacylglycerol, and phosphor ylcholine on SM hydrolysis induced by purified rat intestinal alkaline SMas e in the presence of 10 nM taurocholate. It was found that various phosphol ipids including PC, phosphatidylserine (PS), phosphatidylinositol (PI), pho sphatidylethanolamine (PE), and phosphatidic acid (PA) inhibit alkaline SMa se activity in a dose-dependent manner, with the degree of inhibition being in the order PA > PS > PI > PC > PE. Similar inhibition was also seen in a buffer of pH 7.4, which is close to the physiologic pH in the middle of th e small intestine. When the effects of hydrolytic products of PC were studi ed, lyso-PC, oleic acid, and 1,2-dioleoyl glycerol also inhibited alkaline SMase activity, whereas phosphorylcholine enhanced SMase activity. However, in the absence of bile salt, acid phospholipids including PA, PS, PI mildl y stimulated alkaline SMase activity whereas PC and PE had no effect. It is concluded that in the presence of bile salts, glycerophospholipids and the ir hydrolytic products inhibit intestinal alkaline SMase activity. This may contribute to the slow rate of SM digestion in the upper small intestine. (C) Elsevier Science Inc. 2000. All rights reserved.