Bacterial metabolism of 5-aminosalicylic acid. Initial ring cleavage

Biochem J. 1992 Mar 15;282 ( Pt 3)(Pt 3):675-80. doi: 10.1042/bj2820675.

Abstract

The metabolism of 5-aminosalicylate (5AS) by a bacterial strain, Pseudomonas sp. BN9, was studied. Intact cells of Pseudomonas sp. BN9 grown with 5AS oxidized 5AS and 2,5-dihydroxybenzoate (gentisate), whereas cells grown with gentisate oxidized only the growth substrate of all substituted salicylates tested. Cell extracts from Pseudomonas sp. BN9 catalysed the stoichiometric reaction of 1 mol of oxygen with 1 mol of 5AS to a metabolite with an intense u.v.-absorption maximum at 352 nm (pH 8.0). This metabolite was accumulated under neutral conditions, but was rapidly destroyed at acid pH. It was identified by m.s. and acid-catalysed deamination to fumarylpyruvate (trans-2,4-dioxohept-5-enedioic acid) as cis-4-amino-6-carboxy-2-oxohexa-3,5-dienoate, thus demonstrating direct cleavage of the monohydroxylated substrate 5AS to a non-aromatic ring-fission product. The enzyme responsible for conversion of 5AS was shown to be Fe(II)-dependent and to be distinct from gentisate 1,2-dioxygenase in strain BN9.

MeSH terms

  • Aminosalicylic Acids / metabolism*
  • Cell Extracts / pharmacology
  • Dicarboxylic Acids / metabolism
  • Dioxygenases*
  • Hydrogen-Ion Concentration
  • Mesalamine
  • Moraxella / metabolism*
  • Oxygen / pharmacokinetics
  • Oxygenases / isolation & purification
  • Pseudomonas / metabolism*

Substances

  • Aminosalicylic Acids
  • Cell Extracts
  • Dicarboxylic Acids
  • fumarylpyruvate
  • Mesalamine
  • Oxygenases
  • 5-aminosalicylic acid 1,2-dioxygenase
  • Dioxygenases
  • gentisate 1,2-dioxygenase
  • Oxygen