Ceramide plays an important role in regulating cell proliferation and apopt
osis. Recent studies indicate that generation of ceramide in the intestine
from sphingomyelin hydrolysis may be implicated in colon cancer development
. The enzymes that catalyze the further hydrolysis of ceramide in the intes
tine have, however, not been well investigated. Our data reveal the existen
ce of a ceramidase (EC 3.5.1.23) in rat intestinal mucosa with an optimal p
H of 7.0. One milligram of mucosal protein is able to hydrolyze 44.0 +/- 9.
6 nmol of ceramide in I hr. The activity is low in the proximal duodenum an
d increases to a plateau in the proximal jejunum. The activity is then simi
lar throughout the small intestine, until it declines in the distal part of
ileum. Some activity is also detectable in the colon. The activity increas
es slightly in the presence of monomeric bile salt concentrations and sharp
ly at the critical micellar concentration. Similar patterns were observed f
or both primary (taurocholate) and secondary (taurodeoxycholate) bile salts
. The addition of Triton X-100 enhances the ceramidase activity at optimal
bile salt concentration. The reaction is linear with time for the first 20
min and the hydrolytic rate declines slowly thereafter. Finally, the activi
ty shows a considerable resistance against tryptic degradation, as 71% of t
he ceramidase activity remained when the homogenates were preincubated with
high concentrations of trypsin. Intestinal mucosa also has a ceramide synt
hesis activity, with a distribution pattern generally paralleling ceramide
hydrolysis activity. In conclusion, intestinal neutral ceramidase has a dis
tinct distribution pattern and bile salt dependence, which enables it to co
llaborate with intestinal sphingomyelinase in hydrolysis of sphingomyelin.