Isolation of S-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]-3-thiolactic acid, a new metabolite of histidine, from normal human urine and its formation from S-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]cysteine.

Abstract

S-[2-Carboxy-1-(1H-imidazol-4-yl)ethyl]-3-thiolactic acid (CIE-TL), a novel imidazole compound with a sulphur-containing side chain, was isolated from normal human urine by ion-exchange column chromatography, and characterized by physicochemical analyses involving m.s., i.r. spectrophotometry, high-voltage paper electrophoresis and elemental analysis as well as chemical synthesis. CIE-TL was synthesized by the reaction of S-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]cysteine (CIE-Cys) with NaNO2 in HCl. CIE-TL was also formed during enzymic degradation of CIE-Cys by rat liver or kidney homogenate in a phosphate buffer, possibly via the metabolic intermediate S-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]-3-thiopyruvic acid, and this was accompanied by the formation of 3-[(carboxymethyl)thio]-3-(1H-imidazol-4-yl)propanoic acid, a compound previously found in human urine [Kinuta, Yao, Masuoka, Ohta, Teraoka and Ubuka (1991) Biochem. J. 275, 617-621]. These results suggest that CIE-Cys [Kinuta, Ubuka, Yao, Futani, Fujiwara and Kurozumi (1992) Biochem. J. 283, 39-40] is a physiological precursor of the urinary compounds and that L-histidine is metabolized in part via an alternative pathway initiated by the adduction of natural thiol compounds such as cysteine and GSH to urocanic acid, the first catabolite of histidine.