Influence of mode and duration of phenylalanine administration on biochemical parameters in rats of various ages

✍ Scribed by A. Yuwiler; E. Geller

• Publisher: John Wiley and Sons
• Year: 1969
• Tongue: English
• Weight: 597 KB
• Volume: 2
• Category: Article
• ISSN: 0012-1630
• DOI: 10.1002/dev.420020408

✦ Synopsis

Blood and tissue levels of phenylalanine and tyrosine progressively increase during the first two weeks of feeding a phenylalanine-rich diet to weanling rats. During the same time, liver phenylalanine hydroxylase activity and brain serotonin progressively decline. Hepatic tryptophan hydroxylase activity drops quickly to a constant, low level. With the exception of tryptophan hydroxylase, all of these parameters return towards normal upon continuous treatment. The rnagnitude of change varies with the age of the animal at initiation of dietary treatment and arises because of differences in effective dosage and metabolism as the animals mature. A single phenylalanine injection produces a transient elevation in tissue phenylalanine levels without appreciably affecting brain serotonin. Repeated phenylalanine injections produce more marked alterations in tissue phenylalanine and tyrosine levels, lower activity of tryptophan hydroxylase, and increase serum adrenocorticoids; phenylalanine hydroxylase activity and brain serotonin levels are only marginally affected. These changes seriously complicate interpretations of time-consuming behavioral studies in experimental PKU. phenylketonuria tyrosine tryptophan hydroxylase serotonin corticosterone phenylalanine hydroxylase phenylalanine behavior rats age HENYLKETONURIA presents the enigma of a genetic Pmetabolic defect in liver associated with mental dysfunction. Neurochemical consequences of this primary metabolic error in liver have been sought to correlate biochemistry and behavior, and animal models have been examined to facilitate such studies. Reports that high levels of phenylalanine inhibited phenylalanine hydroxylase activity in vitro (Udenfriend & Cooper, 1952) and that dietary loading with tyrosine inhibited the enzyme in viuo (Auerbach, Waisman, & Wyckoff, 1958) prompted the use of these amino acids to produce experimental phenylketonuria. Both dietary overloading (Auerbach et al., 1958; Yuwiler &