Dunlop D S, Yang X R, Lajtha A
Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY 10962.
Biochem J. 1994 Sep 1;302 ( Pt 2)(Pt 2):601-10. doi: 10.1042/bj3020601.
Increasing the plasma phenylalanine concentration to levels as high as 0.560-0.870 mM (over ten times normal levels) had no detectable effect on the rate of brain protein synthesis in adult rats. The average rates for 7-week-old rats were: valine, 0.58 +/- 0.05%/h, phenylalanine, 0.59 +/- 0.06%/h, and tyrosine, 0.60 +/- 0.09%/h, or 0.59 +/- 0.06%/h overall. Synthesis rates calculated on the basis of the specific activity of the tRNA-bound amino acid were slightly lower (4% lower for phenylalanine) than those based on the brain free amino acid pool. Similarly, the specific activities of valine and phenylalanine in microdialysis fluid from striatum were practically the same as those in the brain free amino acid pool. Thus the specific activities of the valine and phenylalanine brain free pools are good measures of the precursor specific activity for protein synthesis. In any event, synthesis rates, whether based on the specific activities of the amino acids in the brain free pool or those bound to tRNA, were unaffected by elevated levels of plasma phenylalanine. Brain protein synthesis rates measured after the administration of quite large doses of phenylalanine (> 1.5 mumol/g) or valine (15 mumol/g) were in agreement (0.62 +/- 0.01 and 0.65 +/- 0.01%/h respectively) with the rates determined with infusions of trace amounts of amino acids. Thus the technique of stabilizing precursor-specific activity, and pushing values in the brain close to those of the plasma, by the administration of large quantities of precursor, appears to be valid.
将成年大鼠血浆苯丙氨酸浓度提高到高达0.560 - 0.870 mM（超过正常水平的十倍），对脑蛋白合成速率没有可检测到的影响。7周龄大鼠的平均合成速率为：缬氨酸，0.58±0.05%/小时；苯丙氨酸，0.59±0.06%/小时；酪氨酸，0.60±0.09%/小时，总体平均为0.59±0.06%/小时。根据与tRNA结合的氨基酸的比活性计算的合成速率略低于（苯丙氨酸低4%）基于脑游离氨基酸池计算的合成速率。同样，纹状体微透析液中缬氨酸和苯丙氨酸的比活性与脑游离氨基酸池中的几乎相同。因此，脑游离池中缬氨酸和苯丙氨酸的比活性是蛋白质合成前体比活性的良好指标。无论如何，合成速率，无论是基于脑游离池中氨基酸的比活性还是与tRNA结合的氨基酸的比活性，都不受血浆苯丙氨酸水平升高的影响。给予相当大剂量的苯丙氨酸（>1.5 μmol/g）或缬氨酸（15 μmol/g）后测得的脑蛋白合成速率与微量氨基酸输注测定的速率一致（分别为0.62±0.01和0.65±- 0.01%/小时）。因此，通过给予大量前体来稳定前体比活性并使脑中的值接近血浆值的技术似乎是有效的。
