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Clinical Chemistry 15: 397-418, 1969;
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Clinical Chemistry, Vol 15, 397-418, Copyright © 1969 by the American Association for Clinical Chemistry

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

Kihachiro Takahara 1, Shigeko Nakanishi 1, and Samuel Natelson 1

1 Michael Reese Hospital and Medical Center, Department of Biochemistry, Chicago, Ill 60616.

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.

Submitted on April 22, 1968






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Copyright © 1969 by the American Association for Clinical Chemistry.