3,4-Dihydroxyphenylglycol, a metabolite of epinephrine

Abstract

Rabbit brain cortex slices were incubated with 14C-norepinephrine and the amounts of 14C-phenolic acids and 14C-phenolic glycols formed were measured. Pretreatment of rabbits with 2-chloroacetophenone, 300 mg/kg, results in an inhibition of the formation of phenolic acids (especially dihydroxymandelic acid) and a corresponding stimulation of the formation of phenolic glycols. Similar results were observed when the 2-chloroacetophenone was incubated in vitro with brain tissue slices. The concentrations of 2-chloroacetophenone required to inhibit an isolated enzyme preparation of aldehyde dehydrogenase and to inhibit the production of dihydroxymandelic acid in brain tissue slices are similar, which suggests that the effect of 2-chloroacetophenone on norepinephrine metabolism is due to inhibition of aldehyde dehydrogenase. The decrease in aldehyde dehydrogenase activity leads to an increase in substrate available for reduction to phenolic glycols and probably accounts for the observed stimulation of phenolic glycol formation. The effect of 2-chloroacetophenone on norepinephrine metabolism or on isolated aldehyde dehydrogenase could be prevented with glutathione. In addition, the effect on aldehyde dehydrogenase could be reversed with sulfhydryl reagents. This suggests that the interaction of 2-chloroacephenone with sulfhydryl groups may be important in the inhibition of aldehyde dehydrogenase.