Binek-Singer P, Johnson T C
Biochem J. 1982 Aug 15;206(2):407-14. doi: 10.1042/bj2060407.
A prolonged elevation in the concentrations of circulating phenylalanine was maintained in newborn mice by daily injections of phenylalanine and a phenylalanine hydroxylase inhibitor, alpha-methylphenylalanine. The result of this chronic hyperphenylalaninaemia was an accumulation of vacant or inactive monoribosomes that persisted for 18 h of each day. An elongation assay in vitro with brain postmitochondrial supernatants demonstrated that, in addition, there was an equally prolonged decrease in the rates of polypeptide-chain elongation by the remaining brain polyribosomes. Analyses of the free amino acid composition in the brains of hyperphenylalaninaemic mice showed a loss of several amino acids from the brain, particularly the large, neutral amino acids, which are co- or counter-transported across plasma membranes with phenylalanine. When a mixture of these amino acids (leucine, isoleucine, valine, threonine, tryptophan, tyrosine, methionine) was injected into hyperphenylalaninaemic mice, there was an immediate cessation of monoribosome accumulation in the brain and there was no inhibition of the rates of polypeptide-chain elongation. Although the concentrations of the large, neutral amino acids in the brain were partially preserved by treatment of hyperphenylalaninaemic mice with the amino acid mixture, the elevated concentrations of phenylalanine remained unaltered. The amino acid mixture had no detectable effect on brain protein synthesis in the absence of the hyperphenylalaninaemic condition.
通过每日注射苯丙氨酸和一种苯丙氨酸羟化酶抑制剂α-甲基苯丙氨酸，使新生小鼠循环中的苯丙氨酸浓度持续升高。这种慢性高苯丙氨酸血症的结果是，每天有18小时出现空载或无活性单核糖体的积累。用脑线粒体后上清液进行的体外延伸试验表明，此外，剩余脑多核糖体的多肽链延伸速率同样出现了持续时间相同的下降。对高苯丙氨酸血症小鼠脑内游离氨基酸组成的分析显示，脑内几种氨基酸流失，尤其是那些与苯丙氨酸协同或反向转运穿过质膜的大的中性氨基酸。当将这些氨基酸（亮氨酸、异亮氨酸、缬氨酸、苏氨酸、色氨酸、酪氨酸、蛋氨酸）的混合物注射到高苯丙氨酸血症小鼠体内时，脑内单核糖体的积累立即停止，并且多肽链延伸速率未受抑制。尽管用氨基酸混合物治疗高苯丙氨酸血症小鼠可部分维持脑内大的中性氨基酸的浓度，但苯丙氨酸的升高浓度并未改变。在不存在高苯丙氨酸血症的情况下，氨基酸混合物对脑蛋白质合成没有可检测到的影响。
