Glutamine-dependent carbamyl phosphate synthetase during fetal and neonatal life in the rat.
Glutamine-dependent carbamyl phosphate synthetase during fetal and neonatal life in the rat.
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大鼠胎儿和新生儿生命期间谷氨酰胺依赖性氨基甲酰磷酸合成酶。
DOI：
10.1016/0012-1606(74)90177-8
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发表时间：
1974
影响因子：
2.7
通讯作者：
Norbert Freinkel
中科院分区：
文献类型：
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作者：
G. E. Shambaugh;S. Mrozak;Boyd E. Metzger;Norbert Freinkel
嘧啶合成酶，氨甲酰磷酸合成酶II（CP合成酶II）在正常胎儿发育过程中的大鼠和喂养和热量剥夺的新生儿进行了检查。胎盘、肝脏、肠道、尸体和大脑中的CP合成酶II表现出以下共同特性：能够利用氨和L-谷氨酰胺作为底物; N-乙酰基-谷氨酸对活性的增强作用可忽略不计;谷氨酰胺类似物6-重氮-5-氧代-1-正亮氨酸和磷酸化嘧啶尿苷5′-三磷酸对活性的抑制作用。在胎盘和肝外胎儿结构中，CP合成酶II的L-谷氨酰胺的表观Km值在1.1 × 10 − 5 M到2.3 × 10− 5 M之间变化。在脑和胎盘中，妊娠期间连续时间点获得的组织谷氨酰胺浓度至少高出200倍。催化嘧啶生物合成中随后两个步骤的酶，天冬氨酸转氨甲酰酶和二氢乳清酸酶的相对活性在所有测量时间均显著大于CP合成酶II，因此与CP合成酶II可能是胎盘和肝外胎儿组织中嘧啶新生生物合成的限速步骤之一的可能性一致。在胎盘，大脑和新生儿肌肉中获得了一系列观察，以了解每毫克组织DNA的CP合成酶II浓度和总组织DNA的每日增量之间是否存在相关性。在所有这些结构中，在更快速的DNA积累期间观察到更高浓度的酶。某些例外情况也是可以证明的。因此，明显的CP合成酶II活性持续在胎盘超过妊娠16天（当胎盘DNA不再增加）;和新生儿肌肉表现出CP合成酶II活性时，所有的净增量的DNA被废除的热量剥夺。后一种观察结果表明，即使在没有细胞增殖的情况下，酶也可能是有效的（并且可能具有调节意义）。
The pyrimidine-synthesizing enzyme, carbamyl phosphate synthetase II (CP synthetase II) was examined in the rat during normal fetal development and in the fed and calorically deprived neonate. CP synthetase II in the placenta, liver, gut, carcass, and brain showed the following common properties; ability to utilize ammonia as well asl-glutamine as a substrate; negligible enhancement of activity byN-acetyll-glutamate; inhibition of activity by the glutamine analog, 6-diazo-5-oxo-l-norleucine; and by the phosphorylated pyrimidine uridine 5′-triphosphate. ApparentKmvalues forl-glutamine of CP synthetase II in placenta and extrahepatic fetal structures were found to vary from 1.1 to 2.3 × 10−5M. In the brain and placenta, tissue concentrations ofl-glutamine obtained at serial time points during gestation were at least 200-fold higher. Relative activities for the enzymes catalyzing the subsequent two steps in pyrimidine biosynthesis, aspartate transcarbamylase and dihydroorotase, were substantially greater than CP synthetase II at all times measured and therefore were consistent with the possibility that CP synthetase II may be one of the rate-limiting steps in thede novobiosynthesis of pyrimidines in the placenta and extrahepatic fetal tissues. Serial observations were obtained in placenta, brain, and neonatal muscle to see whether correlations could be demonstrated between concentrations of CP synthetase II per milligram of tissue DNA and daily increments in total tissue DNA. In all these structures, higher concentrations of enzyme were observed during periods of more rapid DNA accumulation. Certain exceptions were also demonstrable. Thus, manifest CP synthetase II activity persisted in the placenta beyond day 16 of gestation (when placental DNA no longer increases); and neonatal muscle exhibited CP synthetase II activity when all net increments in DNA were abolished by caloric deprivation. The latter observations have suggested that the enzyme may be operative (and of possible regulatory significance) even in the absence of cellular proliferation.