Fatty acid acylation of mucin by gastric mucosa: effects of sofalcone and sucralfate.
The effects of antiulcer drugs, sofalcone and sucralfate, on the activity of gastric mucosal mucus glycoprotein fatty acyltransferase were investigated. The acyltransferase enzyme, contained in the detergent extracts of the microsomal fraction of rat gastric mucosa, was incubated with the deacylated gastric mucin and palmitoyl-CoA substrates in the presence and absence of drugs, and the formed fatty acid acylated glycoprotein product was quantitated. In the absence of drugs, the enzymatic activity increased proportionally with increased concentrations of both substrates and of enzyme, and gave an apparent Km value of 5.6 X 10(-7) M. Introduction of sofalcone to the reaction mixtures led to an enhancement in the rate of mucus glycoprotein acylation. The rate of enhancement was proportional to sofalcone concentration up to 1.0 X 10(-5) M, with an apparent Km value of 3.7 X 10(-7) M. In contrast to sofalcone, the acyltransferase activity was inhibited by sucralfate. The rate of inhibition of mucus glycoprotein acylation by sucralfate was of the competitive type and at 1.0 X 10(-4) M reached a value of 25%. The apparent KI value calculated from the double-reciprocal plots for sucralfate was 9.1 X 10(-7) M. As the acylation of mucin with fatty acids plays an important role in the maintenance of gastric mucosal integrity, the results suggest that stimulation of the fatty acyltransferase enzyme by sofalcone may be one of the beneficial effects of this drug towards ulcer healing.
Slomiany
B L
BL
Department of Medicine, New York Medical College, Valhalla 10595.
Liau
Y H
YH
Mizuta
K
K
Slomiany
A
A
D000215:Acylation; D000217:Acyltransferases / Q000032:analysis*; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D002599:Chalcone / Q000031:analogs & derivatives / Q000494:pharmacology*; D047188:Chalcones; D005227:Fatty Acids / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009077:Mucins / Q000378:metabolism*; D011427:Propiophenones / Q000494:pharmacology*; D051381:Rats; D013392:Sucralfate / Q000494:pharmacology*
D000897:Anti-Ulcer Agents; D047188:Chalcones; D005227:Fatty Acids; D009077:Mucins; D011427:Propiophenones; C035032:sofalcone; D013392:Sucralfate; D002599:Chalcone; D000217:Acyltransferases