STUDIES ON PROTEIN SYNTHESIS AND AMINO ACID COMPARTMENTATION

在体内测量率的蛋白质合成与放射性标记的前体是有问题的，因为来自蛋白质分解的前体池的蛋白质合成的未标记的氨基酸的相对贡献的不确定性。用羧基标记的脂肪族支链氨基酸作为示踪剂测定体内脑蛋白质合成（ICPS）局部速率的定量放射自显影方法考虑了示踪氨基酸的未标记物质的再循环。大鼠大脑蛋白质合成的速率已被证明在再生神经核中增加，而在出生后大脑发育和衰老期间在大多数大脑区域中减少。皮质醇治疗改变了选择性脑区的lCPS;改变的方向取决于治疗史。对猴子正常睡眠的研究表明，慢波睡眠与许多大脑区域的lCPS速率增加有关。在冬眠的地松鼠中，整个大脑中的lCPS都在深刻而可逆地减少。轻度硫喷妥钠麻醉导致大鼠大脑蛋白质合成率广泛但非常小的下降。一般来说，ICPS的变化可能标志着大脑区域正在经历长期的调整，以响应药物，治疗或生理状态的变化。我们正在研究苯丙酮尿症（PKU）的遗传小鼠模型的大脑蛋白质合成。 已经提出，由于PKU中表现的高苯丙氨酸血症对血脑中性氨基酸转运的竞争性抑制，发育期间脑蛋白质合成速率的降低可能是人类疾病中精神发育迟滞的原因。 我们的研究结果表明，在正常饮食的成年PKU小鼠中，从蛋白质分解到脑中蛋白质合成的前体池中的亮氨酸的再循环显著增加，并且在某些脑区域中脑蛋白质合成的速率降低。

In vivo measurements of rates of protein synthesis with radiolabeled precursors are problematic because of uncertainties about the relative contribution of unlabeled amino acids derived from protein breakdown to the precursor pool for protein synthesis. The quantitative autoradiographic method for the determination of local rates of cerebral protein synthesis (lCPS) in vivo with a carboxyl-labeled, aliphatic, branched-chain amino acid as tracer takes into account recycling of the unlabeled species of the tracer amino acid. Rates of cerebral protein synthesis in rats have been shown to increase in regenerating nerve nuclei and decrease in most brain regions during postnatal brain development and with senescence. Cocaine treatment changes lCPS in selective brain regions; the direction of the changes depends on the history of treatment. Studies of normal sleep in monkeys indicate that slow wave sleep is linked with increased rates of lCPS in many brain regions. In hibernating ground squirrels, lCPS is profoundly and reversibly reduced throughout the brain. Light thiopental anesthesia in rats results in widespread but very small decreases in rates of cerebral protein synthesis. In general, changes in lCPS may mark brain regions undergoing long-term adjustments in response to a drug, a treatment, or a change in physiological state. We are studying cerebral protein synthesis in a genetic mouse model of phenylketonuria (PKU). It has been proposed that a reduction in the rate of cerebral protein synthesis during development due to competitive inhibition of transport of neutral amino acids at the blood brain by the hyperphenylalaninemia manifest in PKU may be the cause of mental retardation in the human disease. Our results indicate that in the adult PKU mouse on a normal diet recycling of leucine from protein breakdown into the precursor pool for protein synthesis in brain is substantially increased and rates of cerebral protein synthesis are decreased in some brain regions.