EFFECTS OF EICOSAPENTAENOIC ACID AND ITS 15-HYDROPEROXY AND 15-HYDROXY DERIVATIVES ON GLUCOSAMINE SYNTHETASE-ACTIVITY IN RABBIT GASTRIC-MUCOSA

The effects of eicosapentaenoic acid and its 15-hydroperoxy and 15-hyd roxy adducts on the activity of glucosamine synthetase, the rate-limit ing enzyme of mucus synthesis, in rabbit gastric antral mucosa were ex amined. 15-Hydroperoxyeicosapentaenoic acid inhibited the glucosamine synthetase activity at concentrations of 10, 20 and 50 mu M. The effec t was concentration-dependent, and the concentration required for 50% inhibition was approximately 20 mu M. Eicosapentaenoic acid and its 15 -hydroxy adduct had no significant effect on the enzyme activity at th e same concentration range. The experiment utilizing Fe2+ revealed tha t the inhibitory effect of 15-hydroperoxyeicosapentaenoic acid on the glucosamine synthetase activity is not due to hydroxy radical which is expected to be formed from the hydroperoxy adduct. These results sugg est that 15-hydroperoxyeicosapentaenoic acid has the potential to redu ce the synthesis of gastric mucus by inhibiting the glucosamine synthe tase activity.