Gautier C, Husson A, Fairand A, Vaillant R
Biol Neonate. 1982;42(1-2):39-45. doi: 10.1159/000241573.
In order to establish whether the postnatal rise in five urea cycle enzyme activities is associated with protein synthesis, the effects of cycloheximide on urea cycle enzyme activities, citrulline and urea productions in vivo and in vitro were studied. A single injection of cycloheximide (10 microgram) 9 h after birth significantly prevented the rise in enzyme activities and citrulline concentration which normally occurred after birth, while the urea level remained unchanged. These data suggest that the postnatal rise in urea cycle enzyme activities might be associated with a protein synthesis. The rate of citrulline synthesis by liver slices was reduced (about 50%) in cycloheximide-treated neonatal liver, while the rate of urea production was not significantly decreased. The results obtained in vivo are in good agreement with in vitro experiments: citrullinogenesis was only affected by cycloheximide treatment. When cycloheximide 10 mM was added to the incubation medium, the ability of control neonatal liver slices to produce citrulline and urea was reduced to 42 and 11%, respectively. Since argininosuccinic acid addition in the medium did not produce a rise in urea synthesis, it is concluded that argininosuccinase is most responsive after incubation in cycloheximide and therefore becomes the rate-limiting step of the urea synthesis.
为了确定出生后五种尿素循环酶活性的升高是否与蛋白质合成有关，研究了环己酰亚胺对体内外尿素循环酶活性、瓜氨酸和尿素生成的影响。出生后9小时单次注射环己酰亚胺（10微克）可显著阻止出生后正常出现的酶活性和瓜氨酸浓度的升高，而尿素水平保持不变。这些数据表明，出生后尿素循环酶活性的升高可能与蛋白质合成有关。在经环己酰亚胺处理的新生肝脏中，肝切片瓜氨酸合成速率降低（约50%），而尿素生成速率没有显著降低。体内实验结果与体外实验结果高度一致：瓜氨酸生成仅受环己酰亚胺处理的影响。当向孵育培养基中加入10 mM环己酰亚胺时，对照新生肝切片产生瓜氨酸和尿素的能力分别降至42%和11%。由于向培养基中添加精氨琥珀酸不会使尿素合成增加，因此得出结论，精氨琥珀酸酶在经环己酰亚胺孵育后反应最为敏感，因此成为尿素合成的限速步骤。
