Isolation and characterization of N-acetyl-S-[2-carboxy-1-(1 H-imidazol-4-yl) ethyl]-L-cysteine, a new metabolite of histidine, from normal human urine and its formation from S-[2-carboxy-1-(1 H-imidazol-4-yl) ethyl]-L-cysteine.
N-Acetyl-S-[2-carboxy-1-(1 H-imidazol-4-yl)ethyl]-L-cysteine (I), a new imidazole compound with a sulfur-containing side chain, was isolated from normal human urine by ion-exchange column chromatography, and characterized by physicochemical analyses involving 1H-NMR spectrometry, mass spectrometry and high-voltage paper electrophoresis as well as chemical synthesis. Approximately five milligrams of crystals of the compound were obtained from 450 litres of the urine. Compound I was synthesized by the addition of N-acetyl-L-cysteine to urocanic acid. The compound was also formed by incubation of S-[2-carboxy-1-(1 H-imidazol-4-yl)ethyl]-L-cysteine (II) with acetyl-CoA in the use of rat kidney or liver homogenate as an enzyme source in a Tris buffer at pH 7.4. Rat brain and spleen homogenates were the less or no effective preparations as the enzyme source. On the other hand, little N-acetylation of a diastereomer of compound II occurred in enzymatic reactions with rat tissue homogenates. Compound I was degraded to compound II by rat kidney or liver homogenate. These results suggest that compound I is a new N-acetylated metabolite of compound II, a compound previously found in human urine, and that the acetylating enzyme recognizes stereoisomerism of asymmetric carbon atoms on the molecule of compound II. These findings support an alternative pathway of L-histidine catabolism initiated by the adduction of glutathione and/or cysteine to urocanic acid, the first catabolite of histidine.
Kinuta
M
M
Department of Biochemistry, Okayama University Medical School, Japan.
Sasaki
K
K
Shimizu
H
H
Ubuka
T
T
D000107:Acetylation; D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000652:urine; D000123:Acetyltransferases; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D002852:Chromatography, Ion Exchange / Q000379:methods; D003545:Cysteine / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000378:metabolism; D006639:Histidine / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000302:isolation & purification / Q000378:metabolism*; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008297:Male; D008956:Models, Chemical; D009928:Organ Specificity; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D014560:Urocanic Acid / Q000378:metabolism
D000596:Amino Acids; D007093:Imidazoles; C102022:N-acetyl-S-(2-carboxy-1-(1H-imidazol-4-yl)ethyl)cysteine; C069010:S-(2-carboxy-1-(1H-imidazol-4-yl) ethyl)cysteine; D006639:Histidine; D000123:Acetyltransferases; D014560:Urocanic Acid; D003545:Cysteine; D000111:Acetylcysteine