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Urea-Cycle Enzymes in Liver Disease

Henry Brown, MD; Mayo E. Brown, PhD; Paul Michelson; William V. McDermott Jr., MD
JAMA. 1967;199(1):35-36. doi:10.1001/jama.1967.03120010079018.
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Enzymes catalyzing urea synthesis are of great importance because this is the primary pathway for nitrogen excretion in humans. Of equal importance is the fact that intermediates formed in the urea cycle enter into almost every known metabolic pathway. The urea-cycle enzymes are widely distributed in the plant and animal kingdom, but it is the five known hepatic enzymes with which we are concerned here.1 The enzymes are carbamyl phosphate synthetase (CPS), ornithine transcarbamylase (OTC), argininosuccinic acid synthetase, argininosuccinase, and arginase. They may be isolated in very pure form from liver homogenates and measured quantitatively. In practice, however, activity measurements in liver homogenates are used as an indication of amount of enzymes present.

Through the action of the first urea-cycle enzyme, CPS, the metabolite carbamyl phosphate is formed from the union of ammonia, carbon dioxide, and adenosine triphosphate (ATP) (Figure). Carbamyl phosphate plays a key role at a critical

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