SIMULATION OF UREA CYCLE - CORRELATION OF EFFECTS DUE TO INBORN-ERRORS IN CATALYTIC PROPERTIES OF ENZYMES WITH CLINICAL-BIOCHEMICAL OBSERVATIONS
SIMULATION OF UREA CYCLE - CORRELATION OF EFFECTS DUE TO INBORN-ERRORS IN CATALYTIC PROPERTIES OF ENZYMES WITH CLINICAL-BIOCHEMICAL OBSERVATIONS
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DOI：
10.1038/icb.1977.26
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发表时间：
1977-01-01
期刊：
影响因子：
--
通讯作者：
NICHOL, LW
中科院分区：
文献类型：
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作者：
KUCHEL, PW;ROBERTS, DV;NICHOL, LW
稳态速率方程是根据从文献中获得的描述尿素循环中4种酶催化反应动力学的信息编写的。这些方程被公式化成一组，它也考虑了循环外的输入和输出化合物的通量。对这组方程进行数值积分，采用所选择的参数近似于正常肝脏中尿素循环的操作。结果是中间代谢物浓度的模式，这形成了反映代谢先天错误影响的模式比较的基础。后者是通过改变数值积分中指定的动力学参数来计算的。对观察到的临床症状、高氨血症I型和II型、高精氨酸血症、瓜氨酸血症和精氨酸琥珀酸尿症进行了讨论。
Steady-state rate equations are written on the basis of information obtained from the literature describing the kinetics of the 4 enzyme-catalyzed reactions comprising the urea cycle. These equations are formulated into a set which also accounts for fluxes of input and output compunds external to the cycle. Numerical integration of this set of equations was performed employing parameters selected to approximate those pertaining to the operation of the urea cycle in normal liver. The result was a pattern of intermediate metabolite concentrations, which formed a basis for the comparison of patterns reflecting the effects of inborn errors of metabolism. The latter were calculated by varying specified kinetic parameters in the numerical integration. Each of the observed clinical syndromes, hyperammonemia types I and II, hyperargininemia, citrullinemia and argininosuccinicaciduria were discussed.