Species differences in L-tryptophan-kynurenine pathway metabolism

Quantification of anthranilic acid and its related enzymes

Suwako Fujigaki, Kuniaki Saito, Masao Takemura, Hidehiko Fujii, Hisayasu Wada, Akio Noma, Mitsuru Seishima

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Anthranilic acid (AA) has attracted considerable attention as one of the L-tryptophan-kynurenine pathway metabolites in the central nervous system. In this study, a highly sensitive and accurate method for the quantification of AA has been developed using reversed-phase high-performance liquid chromatography with electrochemical detection. Serum and cerebrospinal fluid (CSF) AA concentrations in different animal species were measured. CSF AA concentrations in rabbits were 1.1 ± 0.1 nmol/liter, which were 5.7-33.0 times lower than those in other species studied. Serum AA concentrations, however, were slightly higher in rabbits than in other species. In contrast, the concentrations of L-kynurenine (L-KYN) in both serum and CSF were substantially higher in rabbits than in other species. Tissue kynurenine pathway enzymes, indoleamine 2,3-dioxygenase (IDO), tryptophan 2,3- dioxygenase, kynurenine 3-hydroxylase, and kynureninase were determined in rabbits, rats, gerbils, and mice. These enzymes varied among species, especially lung IDO activities in rabbits were 146-516 times higher than those found in other species, but rabbit liver kynurenine 3-hydroxylase activities were lower by one order of magnitude than those of the other species tested. Furthermore, brain kynurenine 3-hydroxylasae activities were 12.3-23.2 times higher in gerbils than those in the other species tested. In addition, AA concentrations in serum following intravenous administration of L-KYN (5 mg/kg) were also measured in rabbits. AA levels peaked sharply within 5 min after administration and decreased in a time-dependent manner. At 5 min after administration, CSF L-KYN and AA concentrations were also increased by 1.76- and 2.56-fold, respectively, compared with basal levels. Increased AA concentrations in CSF following L-KYN administration may reflect the entry of AA into the CSF after conversion to AA in systemic tissue and/or the local synthesis of AA from L-KYN in the CNS.

Original languageEnglish
Pages (from-to)329-335
Number of pages7
JournalArchives of Biochemistry and Biophysics
Volume358
Issue number2
DOIs
Publication statusPublished - 15-10-1998
Externally publishedYes

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Kynurenine
Metabolism
Tryptophan
Cerebrospinal fluid
Enzymes
Cerebrospinal Fluid
Rabbits
Kynurenine 3-Monooxygenase
Indoleamine-Pyrrole 2,3,-Dioxygenase
Gerbillinae
kynureninase
Serum
anthranilic acid
Tryptophan Oxygenase
Tissue
High performance liquid chromatography
Neurology
Reverse-Phase Chromatography
Metabolites
Intravenous Administration

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology

Cite this

Fujigaki, Suwako ; Saito, Kuniaki ; Takemura, Masao ; Fujii, Hidehiko ; Wada, Hisayasu ; Noma, Akio ; Seishima, Mitsuru. / Species differences in L-tryptophan-kynurenine pathway metabolism : Quantification of anthranilic acid and its related enzymes. In: Archives of Biochemistry and Biophysics. 1998 ; Vol. 358, No. 2. pp. 329-335.
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Species differences in L-tryptophan-kynurenine pathway metabolism : Quantification of anthranilic acid and its related enzymes. / Fujigaki, Suwako; Saito, Kuniaki; Takemura, Masao; Fujii, Hidehiko; Wada, Hisayasu; Noma, Akio; Seishima, Mitsuru.

In: Archives of Biochemistry and Biophysics, Vol. 358, No. 2, 15.10.1998, p. 329-335.

Research output: Contribution to journalArticle

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T1 - Species differences in L-tryptophan-kynurenine pathway metabolism

T2 - Quantification of anthranilic acid and its related enzymes

AU - Fujigaki, Suwako

AU - Saito, Kuniaki

AU - Takemura, Masao

AU - Fujii, Hidehiko

AU - Wada, Hisayasu

AU - Noma, Akio

AU - Seishima, Mitsuru

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