Cleavage of Canavaninosuccinic Acid by Human Liver To Form Guanidinosuccinic Acid, a Substance Found in the Urine of Uremic Patients

[摘要] Guanidinosuccinic acid (GSA) has been isolated in substantial quantities from the urine of uremic patients ( 1 ). Attempts to form this compound by transamidination from canavanine and arginine to aspartic acid were unsuccessful. A possible pathway has been found for GSA formation. Human liver homogenate splits canavaninosuccinic acid (CSA) to form homoserine and GSA. Optimum pH is at 8.7-8.8. The reaction proceeds best under anaerobic conditions. Reduced lipoic acid must be present for the reaction. NADH, NADPH, GSH, cysteine, ascorbic acid, NaCN, Fe++, and reduced CoA, dithiothreitol, and BAL cannot be substituted for the lipoic acid. BAL, NADH, NADPH, Fe++, and Co++ act as inhibitors for the reaction. A nondialyzable inhibitor also is present in the liver and can be washed out with water.More than 90% of GSA incubated with various tissues and administered subcutaneously to intact rats was recovered unchanged. It is suggested that GSA is an end product of metabolism in the human.

[学科分类] 过敏症与临床免疫学