Disease relevance of alpha-Methylphenylalanine

• Comparison of alpha-methylphenylalanine and p-chlorophenylalanine as inducers of chronic hyperphenylalaninaemia in developing rats [1].
• Developing rats treated with alpha-methylphenylalanine, showing no growth deficit or signs of toxicity (e.g. cataracts), appear to be a more suitable model for the human disease of phenylketonuria [1].
• In the first treatment, pregnant rats were injected subcutaneously with alpha-methylphenylalanine (to inhibit maternal liver phenylalanine hydroxylase) at a dosage of 30 mg/100 g body weight plus phenylalanine supplementation (to increase maternal and fetal plasma phenylalanine) at a dosage of 60 mg/100 g body weight two times daily [2].

Psychiatry related information on alpha-Methylphenylalanine

• Postnatal alpha-methylphenylalanine treatment effects on adult mouse locomotor activity and avoidance learning [3].

High impact information on alpha-Methylphenylalanine

• alpha-Methylphenylalanine reduces the phenylalanine hydroxylase activity of rat liver by 75 percent [4].
• The very low potency observed with H-Tyr-D-Orn-N alpha MePhe-Glu-NH2 (N alpha MePhe = N alpha-methylphenylalanine) and H-Tyr-D-Orn-Tic-Glu-NH2 indicated that N alpha-alkylation at the 3-position is detrimental to activity [5].
• However, the effects were not additive, in that the depletion caused by alpha-methylphenylalanine was greater, not less, than that after treatment with both it and phenylalanine [6].
• The presence of alpha-methylphenylalanine in newborn mice inhibited 65-70% of hepatic phenylalanine hydroxylase activity within 12 h [7].
• Thus, the effect of l-phenylalanine plus alpha-methylphenylalanine on the endogenous protein kinase and phosphatase activities was examined and the results demonstrated that these drugs have an inhibitory effect on calcium/calmodulin-dependent protein kinase II and protein phosphatase type 1 [8].

Biological context of alpha-Methylphenylalanine

• Furthermore, addition of L-phenylalanine plus alpha-methylphenylalanine decreased the in vitro phosphorylation of both 160 kDa neurofilaments and alpha-tubulin [9].
• Previous studies on the effect of hyperphenylalaninaemia on the development of the muscarinic acetylcholine receptor in the cerebrum of the rat, using alpha-methylphenylalanine-induced hyperphenylalaninaemia, have shown a gradual and steady decrease in the number of binding sites for this neurotransmitter [10].

Anatomical context of alpha-Methylphenylalanine

• Effects of alpha-methylphenylalanine plus phenylalanine treatment during development on myelin in rat brain [11].

Associations of alpha-Methylphenylalanine with other chemical compounds

• The first group was treated pre- and postnatally with Phe and alpha-methylphenylalanine (a phenylalanine hydroxylase inhibitor) [12].
• Effect of phenylalanine, p-chlorophenylalanine and alpha-methylphenylalanine on glucose uptake in vitro by the brain of young rats [13].
• Chronic hyperphenylalaninemia maintained with the aid of a suppressor of phenylalanine hydroxylase, alpha-methylphenylalanine, increases the glycine concentration and the phosphoserine phosphatase activity of the developing rat brain but not that of liver or kidney [14].
• Isoenzyme composition of hepatic phenylalanine hydroxylase in developing rats after treatment with cortisol, alpha-methylphenylalanine and p-chlorophenylalanine in vivo [15].

Gene context of alpha-Methylphenylalanine

• alpha-Methylphenylalanine is a very weak competitive inhibitor of rat liver phenylalanine hydroxylase in vitro but a potent suppressor in vivo [1].

Analytical, diagnostic and therapeutic context of alpha-Methylphenylalanine

• Animal models of PKU used in this study were induced by daily subcutaneous injections of pups with alpha-methylphenylalanine plus phenylalanine in utero and postnatally from day 4 to day 14 [16].

References