1. Academic Validation
  2. Inhibition of phenylalanine hydroxylase, a pterin-requiring monooxygenase, by oudenone and its derivatives

Inhibition of phenylalanine hydroxylase, a pterin-requiring monooxygenase, by oudenone and its derivatives

  • J Antibiot (Tokyo). 1982 Apr;35(4):458-62. doi: 10.7164/antibiotics.35.458.
S Koizumi T Nagatsu H Iinuma M Ohno T Takeuchi H Umezawa
Abstract

Phenylalanine hydroxylase was shown to be inhibited by oudenone and its derivatives in vitro. At a concentration of 2.3 x 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-(3,4-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 x 10(-5) M. 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.

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