Isolation and characterization of 3-[(carboxymethyl)thio]-3-(1H-imidazol-4-yl)propanoic acid from human urine and preparation of its proposed precursor, S-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]cysteine.
3-[(Carboxymethyl)thio]-3-(1H-imidazol-4-yl)propanoic acid (I) was isolated from healthy human urine by using ion-exchange column chromatography, and characterized by physicochemical analyses involving i.r., m.s. and n.m.r. spectrometries as well as chemical synthesis. The urinary content was 0.04-0.07 mumol/l. Compound (I) was synthesized by the addition of mercaptoacetic acid to urocanic acid. In order to establish the origin of the compound. S-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]cysteine (II) and S-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]glutathione (III) were produced by similar reactions of urocanic acid with cysteine and GSH respectively. The yield of compound (II) was markedly increased by sunlight irradiation of the reaction mixture or by the use of cis-urocanic acid rather than the trans isomer. Incubation of compound (II) with rat liver homogenate in a phosphate buffer, pH 7.40, formed a major and some minor products of enzymic degradation, one of which was identified with compound (I). Exposure of rats to the sunlight for 2 days resulted in increase of the epidermal content of trans-urocanic acid from the normal value of 0.38 to 1.70 micrograms/mg wet wt. of skin, accompanied by formation de novo of the epidermal cis isomer. After sunlight irradiation, the content of the trans isomer decreased at a constant rate of 0.03 micrograms/mg wet wt. of skin per day, whereas the cis isomer was eliminated more quickly, having a phase of rapid decrease in the early period. From these results we suggest that compound (I) may participate in the metabolism of urocanic acid and natural thiol compounds such as cysteine and GSH.
Kinuta
M
M
Department of Biochemistry, Okayama University Medical School, Japan.
Yao
K
K
Masuoka
N
N
Ohta
J
J
Teraoka
T
T
Ubuka
T
T
D003545:Cysteine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000652:urine; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000737:chemistry / Q000652:urine*; D008099:Liver / Q000201:enzymology; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D011498:Protein Precursors / Q000652:urine*; D012867:Skin / Q000378:metabolism / Q000528:radiation effects; D013055:Spectrophotometry, Infrared; D013237:Stereoisomerism; D013472:Sunlight; D014560:Urocanic Acid / Q000378:metabolism
D007093:Imidazoles; D011498:Protein Precursors; C069009:3-((carboxymethyl)thio)-3-(1H-imidazol-4-yl)propanoic acid; C069010:S-(2-carboxy-1-(1H-imidazol-4-yl) ethyl)cysteine; D014560:Urocanic Acid; D005978:Glutathione; D003545:Cysteine