Effects of phospholipids on
sphingomyelin hydrolysis induced by
intestinal alkaline sphingomyelinase:
An in vitro study
Jian-Jun Liu, Åke Nilsson, and Rui-Dong Duan
Department of Cell Biology 1, Department of Medicine, University Hospital of Lund,
Lund, Sweden
Digestion of dietary sphingomyelin (SM) is catalyzed by intestinal alkaline sphingomyelinase (SMase) and may
have important implications in colonic tumorigenesis. Previous studies demonstrated that the digestion and
absorption of dietary SM was slow and incomplete and that the colon was exposed to SM and its hydrolytic
products including ceramide. In the present work, we studied the influences of glycerophospholipids and
hydrolytic products of phosphatidylcholine (PC; i.e., lyso-PC, fatty acid, diacylglycerol, and phosphorylcholine)
on SM hydrolysis induced by purified rat intestinal alkaline SMase in the presence of 10 mM taurocholate. It was
found that various phospholipids including PC, phosphatidylserine (PS), phosphatidylinositol (PI), phosphati-
dylethanolamine (PE), and phosphatidic acid (PA) inhibit alkaline SMase 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 the small intestine. When the effects of
hydrolytic products of PC were studied, 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, and PI mildly stimulated alkaline SMase activity whereas PC and PE had no
effect. It is concluded that in the presence of bile salts, glycerophospholipids and their hydrolytic products inhibit
intestinal alkaline SMase activity. This may contribute to the slow rate of SM digestion in the upper small
intestine. (J. Nutr. Biochem. 11:192–197, 2000) © Elsevier Science Inc. 2000. All rights reserved.
Keywords: sphingomyelin digestion; alkaline sphingomyelinase; phosphatidylcholine; phosphatidylinositol;
phosphatidylethanolamine; phosphatidylserine; phosphatidic acid; diacylglycerol; fatty acid; phosphorylcholine
Introduction
Sphingomyelin (SM) is not only a constituent of cell
membranes but also a dietary component. In milk and most
dairy products, SM is the major phospholipid, the amount
being equal to or higher than that of phosphatidylcholine
(PC).
1–3
SM is also present to a considerable extent in eggs,
meat, and fish.
4
Recent studies have indicated that digestion
of SM may have important implications in colonic tumori-
genesis.
5
Administration of SM has been shown to reduce
the number of aberrant colonic crypt foci and to decrease
the proportion of carcinomas to adenomas induced by
1,2-dimethylhydrazine.
6,7
A significant decrease in sphin-
gomyelinase (SMase) activity has been recently demon-
strated to be associated with human colonic adenoma,
carcinoma, and adenomatous polyposis.
8,9
SM is hydrolyzed by SMase and at least three types of
SMase have been identified based on their optimal pH
values. Acid SMase is a lysosomal enzyme with an optimal
pH of 4.5, and neutral SMase is a membrane-bound enzyme
with an optimal pH of 7.5.
10
Both acid and neutral SMases
are common intracellular enzymes and it is unlikely that
their role in SM digestion in the intestinal lumen are
important. Nilsson
11
identified in both rat intestinal tract
and human intestinal content a unique SMase, which was a
brush-border enzyme and preferred an alkaline pH of 9.0.
Address correspondence to Dr. Rui-Dong Duan, Department of Cell
Biology 1, EB-Blocket, University Hospital of Lund, S-221 85 Lund,
Sweden
Received September 22, 1999; accepted January 5, 2000.
J. Nutr. Biochem. 11:192–197, 2000
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