Effects of bile diversion in rats on intestinal sphingomyelinases and ceramidase.
Alkaline sphingomyelinase (Alk-SMase) and neutral ceramidase (N-CDase) in the intestinal microvillar membrane are responsible for dietary sphingomyelin digestion. The activities of the enzymes require the presence of bile salt, and the enzymes can be released into the gut lumen in active forms by bile salts and trypsin. It is unclear to what extent that the intestinal presence of bile salts is critical for the intraluminal activity of these enzymes. We compared the activities of Alk-SMase, N-CDase, and other types of SMases in control and permanently bile diverted rats. In the intestinal tract of control rats, the activity of Alk-SMase was profoundly higher than those of acid and neutral SMases. Bile diversion reduced Alk-SMase activity by 85% in the small intestinal content, and by 68% in the faeces, but did not significantly change the activity in the intestinal mucosa. Western blot showed a marked reduction of the enzyme in the intestinal lumen but not mucosa. N-CDase activities both in the intestinal mucosa and content were reduced by bile diversion. Bile diversion also decreased aminopeptidase N activity in the content and increased that in the mucosa, but had no effects on that of alkaline phosphatase. In conclusion, the presence of bile salts is important for maintaining high intraluminal levels of Alk-SMase and N-CDase, two key enzymes for hydrolysis of sphingomyelin in the gut. We speculate that the sphingomyelin hydrolysis in cholestatic conditions is impaired not only by reduced hydrolytic activity but also by deficient dissociation of the enzymes from the membrane.
Duan
R D
RD
Gastroenterology Lab., Biomedical Center, B11, Lund University, S-221 84 Lund, Sweden. rui-dong.duan@med.lu.se
Verkade
H J
HJ
Cheng
Y
Y
Havinga
R
R
Nilsson
A
A
D000581:Amidohydrolases / Q000378:metabolism*; D000818:Animals; D001646:Bile / Q000502:physiology*; D055572:Ceramidases; D003106:Colon / Q000201:enzymology; D005243:Feces / Q000201:enzymology; D007413:Intestinal Mucosa / Q000378:metabolism*; D007421:Intestine, Small / Q000201:enzymology; D007422:Intestines / Q000201:enzymology*; D008297:Male; D055576:Neutral Ceramidase; D051381:Rats; D017208:Rats, Wistar; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism*
D013108:Sphingomyelin Phosphodiesterase; D000581:Amidohydrolases; C526748:Asah2 protein, rat; D055572:Ceramidases; D055576:Neutral Ceramidase