Studies on the phenylalanine hydroxylase system in vivo. An in vivo assay based on the liberation of deuterium or tritium into the body water from ring-labeled L-phenylalanine.

  title={Studies on the phenylalanine hydroxylase system in vivo. An in vivo assay based on the liberation of deuterium or tritium into the body water from ring-labeled L-phenylalanine.},
  author={S. Milstien and S. Kaufman},
  journal={The Journal of biological chemistry},
  volume={250 12},
The rate of release of deuterons into the body water from 2,3,4,5,6-pentadeutero-L-phenylalanine has been shown to be a valid measure of the activity of the phenylalanine hydroxylase system in vivo. At a dose of 0.5 g/kg, the rate of release of deuterons is linear for 60 to 90 min. Male rats, which had previously been shown to have 22 to 25% more phenylalanine hydroxylase activity in liver extracts than female rats, produced deuterons from deuterated phenylalanine at a rate 20 to 30% greater… Expand
Phenylalanine conversion to tyrosine: comparative determination with L-[ring-2H5]phenylalanine and L-[1-13C]phenylalanine as tracers in man.
The compared rates of phenylalanine conversion to tyrosine based on the following pairs of primed, continuous tracer infusions administered simultaneously indicate the need for caution in interpreting kinetic aspects of phenolalanine metabolism when based on isotopic data from multideuterated phenylAlanine. Expand
A tritium-release in vivo assay of dopamine-beta-hydroxylase activity in sympathetic neurons.
It is suggested that accumulation of tritiated water in the whole animal after the administration of [β- 3 H]dopamine can be used as an index of dopamine-β-hydroxylase activity in sympathetic neurons. Expand
Studies on the production and assessment of experimental histidinemia in the rat.
It is demonstrated that histidine ammonia-lyase is the rate-limiting factor in L-histidine degradation in the rat and the potential usefulness of DL-hydrazinoimidazolylproprionic acid in the production of an animal model for histidinemia is discussed. Expand
Quantitation of deuterated and non-deuterated phenylalanine and tyrosine in human plasma using the selective ion monitoring method with combined gas chromatography-mass spectrometry. Application to the in vivo measurement of phenylalanine-4-monooxygenase activity.
From the several derivatives investigated, the N- or N,O-trifluoroacetyl methyl esters were found to be the most suitable for purposes of quantitative analysis and an in vivo determination of phenylalanine-4-monooxygenase activity in humans is possible. Expand
Glucagon stimulation of phenylalanine metabolism. The effects of acute and chronic glucagon treatment.
The absence of p-hydroxyphenylpyruvate in the urine and the increased oxidation of phenylalanine imply that, in rats administered glucagon chronically, flux of p -hydroxylpine dioxygenase through the p-Hydroxyp Henyllactate dioXYgenase reaction was increased, and this could indicate rate limiting, as indicated by increased urinary excretion. Expand
Measurement of phenylalanine hydroxylating activity in vivo
Results indicate that labeling with18O cannot be used to measure the turnover rate of brain catecholamines as previously proposed, and the incorporation of18O2 into endogenous constituents might serve as a useful diagnostic procedure for some metabolic disorders, such as phenylketonuria. Expand
A model of human phenylalanine metabolism in normal subjects and in phenylketonuric patients.
  • S. Kaufman
  • Medicine, Biology
  • Proceedings of the National Academy of Sciences of the United States of America
  • 1999
The derivation of a quantitative model of phenylalanine metabolism in humans is described. The model is based on the kinetic properties of pure recombinant human phenylalanine hydroxylase and onExpand
Spectroscopic investigation of ligand interaction with hepatic phenylalanine hydroxylase: evidence for a conformational change associated with activation.
Results suggest that activation of phenylalanine hydroxylase results in a conformation change and the exposure of buried tryptophan(s) and possibly a cysteine residue. Expand
Effects of experimental diabetes on rat hepatic phenylalanine hydroxylase in vivo.
The stimulated levels of phenylanine hydroxylase activity in liver extracts from streptozotocin-induced diabetic rats have been correlated with an increased rate of phenylalanine catabolism in vivo, but this effect is not seen in diabetic animals concurrently treated with insulin. Expand
Hyperphenylalaninemia due to a deficiency of biopterin. A variant form of phenylketonuria.
The results indicate that the child suffers from a variant form of phenylketonuria--a deficiency of a functional phenylalanine hydroxylating system secondary to a defect in biosynthesis of biopterin. Expand