Formation of S-[2-carboxy-1-(1H-imidazol-4-yl) ethyl]glutathione, a new metabolite of L-histidine, from cis-urocanic acid and glutathione by the action of glutathione S-transferase

Masahiro Kinuta, Keiko Kinuta, Hiroshi Yamada, Tadashi Abe, Yumi Yoshida, Kenta Araki, Shu Ai Li, Atsushi Otsuka, Akira Nakanishi, Yoshinori Moriyama, Kohji Takei

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Exposure of the skin to sunlight results in an increase of the content of epidermal transurocanic acid, a key metabolite of L-histidine, and also in occurrence of the isomerization of tran-urocanic acid to the cis isomer. S-[2-Carboxy-1-(1H-imidazol-4-yl)ethyl]-glutathione (GS(CIE)), an adduct of urocanic acid and glutathione, is a presumed origin of a urinary compound S-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]-L-cysteine (Cys(CIE)). The formation of GS(CIE) is stimulated by exposing the skin to sunlight irradiation. In this study we investigated an enzymatic formation of GS(CIE) from glutathione and cisurocanic acid by incubation with rat liver extract that contained glutathione S-transferase (GST) at high activity. The formation of GS(CIE) was suppressed significantly when a liver extract depleted of GST activity was used. Enzymatic degradation of GS(CIE) with γ-glutamyl transpeptidase resulted in the formation of N-{S-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]-L-cysteinyl)glycine, a metabolic intermediate between the glutathione adduct and Cys(CIE). A hydrolyzed product of GS(CIE) by HCI was identical with the urinary Cys(CIE). Compounds were analyzed by high-voltage paper electrophoresis, capillary electrophoresis, and fast atom bombardment mass spectrometry. From these results, we suggest that GS(CIE) formed from cis-urocanic acid and glutathione is an origin of the urinary compound Cys(CIE) and that the formation reaction is catalyzed mostly by the action of GST.

Original languageEnglish
Pages (from-to)3212-3218
Number of pages7
JournalElectrophoresis
Volume24
Issue number18
DOIs
Publication statusPublished - Sep 2003

Fingerprint

NSC 153174
Urocanic Acid
Metabolites
Glutathione Transferase
Histidine
Glutathione
Cysteine
Liver Extracts
Sunlight
cysteinylglycine
Skin
S-(2-carboxy-1-(1H-imidazol-4-yl)ethyl)glutathione
Fast Atom Bombardment Mass Spectrometry
Paper Electrophoresis

Keywords

  • Capillary electrophoresis
  • Glutathione S-conjugate
  • Glutathione S-transferase
  • Imidazole compound
  • Mass spectrometry

ASJC Scopus subject areas

  • Clinical Biochemistry

Cite this

Formation of S-[2-carboxy-1-(1H-imidazol-4-yl) ethyl]glutathione, a new metabolite of L-histidine, from cis-urocanic acid and glutathione by the action of glutathione S-transferase. / Kinuta, Masahiro; Kinuta, Keiko; Yamada, Hiroshi; Abe, Tadashi; Yoshida, Yumi; Araki, Kenta; Li, Shu Ai; Otsuka, Atsushi; Nakanishi, Akira; Moriyama, Yoshinori; Takei, Kohji.

In: Electrophoresis, Vol. 24, No. 18, 09.2003, p. 3212-3218.

Research output: Contribution to journalArticle

Kinuta, Masahiro ; Kinuta, Keiko ; Yamada, Hiroshi ; Abe, Tadashi ; Yoshida, Yumi ; Araki, Kenta ; Li, Shu Ai ; Otsuka, Atsushi ; Nakanishi, Akira ; Moriyama, Yoshinori ; Takei, Kohji. / Formation of S-[2-carboxy-1-(1H-imidazol-4-yl) ethyl]glutathione, a new metabolite of L-histidine, from cis-urocanic acid and glutathione by the action of glutathione S-transferase. In: Electrophoresis. 2003 ; Vol. 24, No. 18. pp. 3212-3218.
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abstract = "Exposure of the skin to sunlight results in an increase of the content of epidermal transurocanic acid, a key metabolite of L-histidine, and also in occurrence of the isomerization of tran-urocanic acid to the cis isomer. S-[2-Carboxy-1-(1H-imidazol-4-yl)ethyl]-glutathione (GS(CIE)), an adduct of urocanic acid and glutathione, is a presumed origin of a urinary compound S-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]-L-cysteine (Cys(CIE)). The formation of GS(CIE) is stimulated by exposing the skin to sunlight irradiation. In this study we investigated an enzymatic formation of GS(CIE) from glutathione and cisurocanic acid by incubation with rat liver extract that contained glutathione S-transferase (GST) at high activity. The formation of GS(CIE) was suppressed significantly when a liver extract depleted of GST activity was used. Enzymatic degradation of GS(CIE) with γ-glutamyl transpeptidase resulted in the formation of N-{S-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]-L-cysteinyl)glycine, a metabolic intermediate between the glutathione adduct and Cys(CIE). A hydrolyzed product of GS(CIE) by HCI was identical with the urinary Cys(CIE). Compounds were analyzed by high-voltage paper electrophoresis, capillary electrophoresis, and fast atom bombardment mass spectrometry. From these results, we suggest that GS(CIE) formed from cis-urocanic acid and glutathione is an origin of the urinary compound Cys(CIE) and that the formation reaction is catalyzed mostly by the action of GST.",
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AU - Kinuta, Masahiro

AU - Kinuta, Keiko

AU - Yamada, Hiroshi

AU - Abe, Tadashi

AU - Yoshida, Yumi

AU - Araki, Kenta

AU - Li, Shu Ai

AU - Otsuka, Atsushi

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AU - Moriyama, Yoshinori

AU - Takei, Kohji

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