Huether G, Kaus R, Neuhoff V
Biochem Med. 1985 Jun;33(3):334-41. doi: 10.1016/0006-2944(85)90008-0.
The elevated phenylalanine concentration in the blood of untreated phenylketonuric children is known to be paralleled by decreased concentrations of other amino acids in the blood and brain tissue. Due to the low availability of other large, neutral amino acids in the brain, protein synthesis in, and the normal development of, the brain are disturbed. A similar effect is observed in suckling rats rendered hyperphenylalaninemic by the daily injection of phenylalanine plus alpha-methylphenylalanine, an in vivo inhibitor of the phenylalanine-hydroxylating pathway in the liver. In this study, the simultaneous injection of lysine is shown to prevent the depletion of amino acids from the blood and brain tissue, and the retardation of brain growth, in suckling hyperphenylalaninemic rats. It is suggested that both amino acids, phenylalanine and lysine, are important rate-limiting substrates for the rapid protein anabolism of developing tissues. In the presence of an excess of phenylalanine, other amino acids, and in relation to its requirement during the phase of hyperplastic growth in particular lysine, are less available from the circulation and limit phenylalanine-stimulated protein synthesis in developing tissues. The supplementation of lysine to developing hyperphenylalaninemic rats prevents the consequences of this effect, i.e., the depletion of amino acids in the blood, and therefore, in the brain tissue, and the retardation of brain growth.
已知未经治疗的苯丙酮尿症儿童血液中苯丙氨酸浓度升高的同时，血液和脑组织中其他氨基酸的浓度会降低。由于大脑中其他大的中性氨基酸的可利用性较低，大脑中的蛋白质合成以及大脑的正常发育会受到干扰。在通过每日注射苯丙氨酸加α-甲基苯丙氨酸（肝脏中苯丙氨酸羟化途径的体内抑制剂）而导致高苯丙氨酸血症的乳鼠中也观察到了类似的效果。在这项研究中，同时注射赖氨酸可防止高苯丙氨酸血症乳鼠血液和脑组织中的氨基酸耗竭以及脑生长迟缓。有人提出，苯丙氨酸和赖氨酸这两种氨基酸都是发育中组织快速蛋白质合成代谢的重要限速底物。在苯丙氨酸过量的情况下，其他氨基酸，特别是在增生性生长阶段其需求量大的赖氨酸，从循环中获取的量较少，从而限制了发育中组织中苯丙氨酸刺激的蛋白质合成。给发育中的高苯丙氨酸血症大鼠补充赖氨酸可防止这种影响的后果，即血液中氨基酸的耗竭，进而防止脑组织中氨基酸的耗竭以及脑生长迟缓。
