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Activities of 5 Krebs-Henseleit (KH) enzymes [carbamyl phosphate synthetase (CPS), ornithine transcarbamylase (OT), argininosuccinic acid synthetase (ASS), argininosuccine acid lyase (AS), and arginase (A)] were determined in liver tissue obtained at laparotomy from 17 patients with alcoholic cirrhosis, and from 19 individuals without liver disease. Specific activities of the 5 enzymes were calculated on the basis of 4 units of reference: wet weight, total N, noncollagen N, and DNA. Specific activities of all 5 enzymes were depressed in the cirrhotic liver. Degree of reduction was similar regardless of which unit of reference was employed to calculate specific activity. Average extent of depression for activity per milligram of DNA was 54 per cent, 37 per cent, 50 per cent, 64 per cent, and 69 per cent for CPS, OT, ASS, AS, and A, respectively. Rate-limiting enzymes for operation of KH cycle were CPS, ASS, and AS in both normal and cirrhotic livers. Extent of loss of these three enzymes in cirrhotic liver measured in vitro correlated with reduction in maximal rate of urea synthesis and with severity of NH4Cl intolerance measured in vivo.
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Accepted: July 1, 1974
Received: March 22, 1974
☆Supported in part by United States Public Health Service Grants AM 15736 and RR00039.
© 1974 Published by Elsevier Inc.