Abstract
Phenylalanine hydroxylase was shown to be inhibited by oudenone and its derivatives in vitro. At a concentration of 2.3×10-3 M, oudenone inhibited phenylalanine hydroxylase by 50%, and some of the oudenone derivatives showed more potent inhibition. The kinetic data have shown that the inhibition by oudenone is competitive with a tetrahydropterin cofactor (6-7-dimethyltetrahydropterin, DMPH4) and noncompetitive with phenylalanine and oxygen. Among 12 oudenone derivatives, there was no parallel structure-activity relationship between the inhibitory effect for phenylalanine hydroxylase and that for tyrosine hydroxylase. A derivative of oudenone, [compound No. 142; 2-(3-(3, 4-dihydroxyphenyl)-1-oxopropyl)cyclohexan-1, 3-dione] showed the most potent inhibition among the oudenone derivatives. It inhibited phenylalanine hydroxylase by 50% at a concentration of 1.8×10-5M. This inhibition was a mixed type with either a tetrahydropterin cofactor, DMPH4, or with the substrate phenylalanine, which was different from the inhibition by oudenone. However, the same noncompetitive inhibition was shown toward oxygen.
