EFFECT OF 13-HYDROPEROXYOCTADECADIENOIC ACID ON THE GLUCOSAMINE SYNTHETASE-ACTIVITY IN RABBIT GASTRIC-MUCOSA

The effect of 13-hydroperoxyoctadecadienoic acid (13-HPODE) on the act ivity of glucosamine synthetase, the rate-limiting enzyme of mucus syn thesis, in rabbit gastric corporal mucosa was examined. 13-HPODE inhib ited the glucosamine synthetase activity at concentrations ranging fro m 10 to 100 mu M. The effect was concentration-dependent, and the conc entration required for 50% inhibition was approximately 20 mu M. Exper iments utilizing Fe2+ and 13-hydroxyoctadecadienoic acid revealed that the inhibitory effect of 13-HPODE on the glucosamine synthetase activ ity is not due to the alcohol adduct and hydroxyl radical which are ex pected to be formed from 13-HPODE, and that the hydroperoxyl functiona l group is a prerequisite. The fact that tert-butyl hydroperoxide exhi bited about 50 times weaker inhibition than 13-HPODE indicates the rel ative specificity of fatty acyl hydroperoxides in the modulation of th e glucosamine synthetase activity. These results suggest that 13-HPODE has the potential to modulate the synthesis of gastric mucus by affec ting the glucosamine synthetase activity.