Inhibition studies of 3-hydroxyanthranilic acid oxygenase from beef liver

D. L. Nandi*, Richard B Silverman

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Quinolinic acid, the final catalytic product of 3hydroxyanthranilic acid oxygenase (3HAO), is involved in a number of neurodegenerative disorders like Huntington's disease. To understand the catalytic reaction mechanism of 3HAO and also develop a probable therapeutic agent for the above mentioned diseased states attempts were made to synthesize 6-halo-3hydroxyanthranilic acids as possible mechanism based inactivators of this enzyme. 6-chloro-3- hydroxyanthranilic acid has been made according to the following scheme: 5-chloro-2-methoxyaniline>5-chloro-2-methoxyisonitrosoacetanilide ->4-chloro-7methoxyisatin-> 6-chloro-3-methoxyanthranilic acid -> 6 chloro3-hydroxyanthranilic acid. TLC showed a single spot in hexane: ether: ethanol: acetic acid solvent (20: 16: 1: 50 ul). H'NMR and HRMS confirmed the structure. 3HAO from beef liver was inhibited by 6-chloro HA. The inhibition was time and concentration dependent. The K, and k-4 values are 8 mM and 7.2 x 103 min ' respectively. It is not known at the present time the nature of the binding site of this inactivator to this enzyme.

Original languageEnglish (US)
JournalFASEB Journal
Volume11
Issue number9
StatePublished - Dec 1 1997

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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