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.
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.
Kinuta
M
M
Department of Biochemistry, Okayama University Medical School, Japan.
Ubuka
T
T
Yao
W B
WB
Zhao
Y Q
YQ
Shimizu
H
H
D000818:Animals; D003545:Cysteine / Q000031:analogs & derivatives* / Q000378:metabolism; D006639:Histidine / Q000378:metabolism*; D006801:Humans; D007093:Imidazoles / Q000302:isolation & purification* / Q000378:metabolism* / Q000652:urine; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D016339:Spectrometry, Mass, Fast Atom Bombardment
D007093:Imidazoles; C069010:S-(2-carboxy-1-(1H-imidazol-4-yl) ethyl)cysteine; C085943:S-(2-carboxy-1-(1H-imidazol-4-yl)-ethyl)-3-thiolactic acid; D006639:Histidine; D003545:Cysteine