Delvalle J A, Greengard O
Biochem J. 1976 Mar 15;154(3):613-8. doi: 10.1042/bj1540613.
Maximum inhibition of phenylalanine hydroxylase activity in the liver (85%) and in the kidney (50%) of suckling rats required the administration of over 9 mumol of p-chlorophenylalanine/10g body weight. Despite the decrease in the total activity from 184 to 34 units per 10g body weight, the injection of as much as 26 mumol of phenylalanine was required for its concentration in plasma to be still considerably elevated 12h later. In rats injected with p-chlorophenylalanine every 48h and with phenylalanine every 24h from 3 to 18 days of age, the hepatic and renal phenylalanine hydroxylase remained inhibited, whereas the activities of three other hepatic enzymes were unchanged. There was about 20% inhibition of brain and body growth, but no interference with the developmental formation of several cerebral enzymes (four dehydrogenases, hexokinase and glutaminase) was detected. In the course of this prolonged treatment, the phenylalanine concentrations in plasma increased gradually; on day 2 and day 8 (measured 12h after the last injection) they were 800 and 1395 nmol/ml respectively; on day 15, 12 and 18h after the usual injection, the values were 2030 and 1030 respectively as opposed to the 96 nmol in untreated rats. This degree of hyperphenylalaninaemia, persisting for 18h per day throughout a critical period of development, fulfils the primary criterion of a suitable animal model for phenylketonuria.
对乳鼠肝脏（85%）和肾脏（50%）中苯丙氨酸羟化酶活性的最大抑制作用，需要给予超过9微摩尔对氯苯丙氨酸/10克体重。尽管每10克体重的总活性从184单位降至34单位，但注射多达26微摩尔苯丙氨酸后，12小时后其血浆浓度仍显著升高。在3至18日龄的大鼠中，每48小时注射对氯苯丙氨酸，每24小时注射苯丙氨酸，肝脏和肾脏中的苯丙氨酸羟化酶仍受到抑制，而其他三种肝脏酶的活性未发生变化。大脑和身体生长受到约20%的抑制，但未检测到对几种脑酶（四种脱氢酶、己糖激酶和谷氨酰胺酶）发育形成的干扰。在这种长期治疗过程中，血浆中的苯丙氨酸浓度逐渐升高；在第2天和第8天（最后一次注射后12小时测量），它们分别为800和1395纳摩尔/毫升；在第15天，在通常注射后12小时和18小时，值分别为2030和1030，而未治疗大鼠的值为96纳摩尔。这种高苯丙氨酸血症程度在发育的关键时期每天持续18小时，符合苯丙酮尿症合适动物模型的主要标准。
