The activities of urea cycle enzymes such as arginine synthetase (AS), ornithine transcarbamylase (OTC) and arginase (Arg.) were determined in the specimens obtained by liver needle biopsy carried out in 67 cases with various liver diseases, and at the same time, in 46 cases, the plasma levels of citrulline, arginine and blood ammonia were also determined for the purpose of clarifying the action of urea cycle in the liver in its pathological conditions and for studying the relationship between the activities of urea cycle enzymes and blood ammonia level.
The following results were obtained.
1. The activities of liver urea cycle enzymes in normal controls (control liver specimens were obtained by resection on operating table at surgery for peptic ulcer from patients with normal liver function) were as follows: AS; 0.79±0.27, OTC; 59.8±15.1 and Arg.; 58.6±12.7μM/mg of soluble protein/60 min. The low level of the activity per mg of soluble protein in AS was fairly remarkable suggesting that the enzymological process synthesizing arginine from citrulline existed at the rate limiting step in urea cycle. The levels of plasma citrulline and arginine were 6.61±1.31 and 8.42±1.09μg/m
l, respectively, and blood ammonia 0.66±0.24μg NH
3-N/m
l,
2. The activities of AS, OTC and Arg. in acute hepatitis were 0.39±0.32, 40.8±17.2 7. The activities of AS, OTC and Arg. in obstructive jaundice were 0.62±0.36, 49.1±13.7 and 42.8±18.9μM/mg of soluble protein/60 min., respectively.Decreased activities were seen in the cases with obstruction due to cancer, but in the cases with obstruction due to cholelithiasis no clear decrease in the activities was observed. The levels of plasma citrulline and arginine were 7.61±2.13 and 8.45±1.59μg/m
l and blood ammonia 0.88±0.30μg NH
3-N/m
l.8. The activities of AS, OTC and Arg. in Banti's syndrome were 0.62±0.30, 54.3±19.4 and 49.6±11.6μM/mg. of soluble protein/60 min., respectively. No relationship was seen between the decrease of the activities of these enzymes and the onset time of this syndrome.and 41.6±21.3μM/mg of soluble protein /60 min., respectively. At the progressive or excerbating stage of acute hepatitis the activities were as follows: AS; 0.31±0.25, OTC; 39.1±20.1 and Arg; 30.6±13.3μM/mg of soluble protein /60 min. On the other hand, at the convalescent stage the activities of AS, OTC and Arg. were 0.53±0.41, 43.6±12.5 and 56.3±21.9μM/mg of soluble protein/60 min., respectively. Generally speaking, the decrease of the activities of these enzymes was nearly in direct proportion to the extent of necrosis of liver cells. The plasma levels of citrulline and arginine were 8.04±2.34 and 8.42±1.09μg/m
l, respectively, and that of ammonia 0.75±0.31 μ g NH
3-N/m
l. The level of citrulline showed a tendency, though slight, to increase.
3. The activities of AS, OTC and Arg. in chronic hepatitis were 0.57±0.39, 51.4±18.9 and 45.8±22.4μM/mg of soluble protein/60 min., respectively, and the plasma levels of citrulline and arginine were 7.09±1.28 and 8.53±2.62μg/m
l, respectively, and that of ammonia 0.83±0.23μg NH
3-N/m
l.
4. The activities of AS, OTC and Arg. in liver cirrhosis were 0.41+0.26, 42.9+12.6 and 43.9±11.9μM/mg of soluble protein/60 min., respectively. The decrease of the activities of these enzymes came next to that of acute hepatitis and a special decrease was observed in the cases at the non-compensatory stage of liver cirrhosis.
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