Binek P A, Johnson T C, Kelly C J
J Neurochem. 1981 Apr;36(4):1476-84. doi: 10.1111/j.1471-4159.1981.tb00589.x.
A chronic hyperphenylalanemia was effectively produced in developing mice by daily administrations of phenylalanine (2 mg/g body wt) and a phenylalanine hydroxylase inhibitor alpha-methyl-D,L-phenylalanine (0.43 mg/g body wt). The presence of alpha-methylphenylalanine in newborn mice inhibited 65-70% of hepatic phenylalanine hydroxylase activity within 12 h. Since this maximum inhibition persisted for 24 h or longer, decreased enzyme activity was maintained by daily administrations. Whereas concentrations of phenylalanine increased approximately 40-fold in both plasma and brain following injection of alpha-methylphenylalanine and phenylalanine, plasma levels of tyrosine were not altered significantly. Concomitant with changes in phenylalanine concentrations we observed the brain polyribosomes' disaggregation, which reached a maximum 3 h after injection and persisted as long as 18 h. Polyribosomes did not become refractory to as many as 10 daily injections of alpha-methylphenylalanine and phenylalanine. In addition to polyribosome disaggregation, chronic hyperphenylalanemia reduced the rates of polypeptide chain elongation on polyribosomes isolated from brain homogenates.
通过每日给予苯丙氨酸（2毫克/克体重）和苯丙氨酸羟化酶抑制剂α-甲基-D，L-苯丙氨酸（0.43毫克/克体重），在发育中的小鼠中有效诱导出慢性高苯丙氨酸血症。新生小鼠体内存在α-甲基苯丙氨酸，在12小时内可抑制肝脏苯丙氨酸羟化酶活性的65%-70%。由于这种最大抑制作用持续24小时或更长时间，通过每日给药维持酶活性降低。注射α-甲基苯丙氨酸和苯丙氨酸后，血浆和脑中的苯丙氨酸浓度增加约40倍，而血浆酪氨酸水平无明显改变。伴随着苯丙氨酸浓度的变化，我们观察到脑多核糖体解聚，注射后3小时达到最大值，并持续长达18小时。多核糖体对多达10次每日注射α-甲基苯丙氨酸和苯丙氨酸并不产生耐受性。除了多核糖体解聚外，慢性高苯丙氨酸血症还降低了从脑匀浆中分离出的多核糖体上多肽链的延伸速率。
