D-Phenylalanine

14,000,000 Leading Edge Experts on the ideXlab platform

Scan Science and Technology

Contact Leading Edge Experts & Companies

Scan Science and Technology

Contact Leading Edge Experts & Companies

The Experts below are selected from a list of 213 Experts worldwide ranked by ideXlab platform

Tsunekazu Yamano - One of the best experts on this subject based on the ideXlab platform.

  • Effects of tetrahydrobiopterin and phenylalanine on in vivo human phenylalanine hydroxylase by phenylalanine breath test.
    Molecular Genetics and Metabolism, 2007
    Co-Authors: Yoshiyuki Okano, Kazuhiko Takatori, Satoshi Kudo, Tomoko Sakaguchi, Minoru Asada, Masahiro Kajiwara, Tsunekazu Yamano
    Abstract:

    Abstract BH 4 administration results in the reduction of blood phenylalanine level in patients with tetrahydrobiopterin (BH 4 )-responsive phenylalanine hydroxylase (PAH) deficiency. The mechanism underlying BH 4 response remains unknown. Here, we studied the effects of BH 4 and phenylalanine on in vivo PAH activity of normal controls using the phenylalanine breath test (PBT) by converting l -[1- 13 C] phenylalanine to 13 CO 2 . Phenylalanine oxidation rates were expressed as Δ 13 C ( 13 CO 2 / 12+13 CO 2 , ‰) and cumulative recovery rates over 120 min (CRR 120 , %; total amount of 13 CO 2 /the administered dose of 13 C-phenylalanine). Under physiological conditions of blood phenylalanine, BH 4 administration reduced the Δ 13 C peak from 40.8‰ to 21.6‰ and CRR 120 from 16.9% to 10.2%. Under high blood phenylalanine conditions, administration of BH 4 increased the Δ 13 C peak from 30.7‰ to 46.0‰, while the CRR 120 was similar between phenylalanine (19.9%) and phenylalanine + BH 4 (21.1%) groups. Corrected Δ 13 C and CRR 120 were calculated against serum phenylalanine levels to remove the effects of phenylalanine loading. After BH 4 administration, the corrected Δ 13 C peak increased from 82.7‰ to 112.6‰, while the corrected CRR 120 was similar (47.6% and 45.6%). These results indicate that phenylalanine worked as a regulator of in vivo PAH by serving as both a substrate and an activator for the enzyme. Excessive dosages of BH 4 inhibited PAH under normal phenylalanine conditions and activated PAH under conditions of high phenylalanine. The regulation system is therefore designed to maintain phenylalanine levels in the human body. Appropriate BH 4 supplementation must be reviewed in patients with BH 4 -responsive PAH deficiency.

  • In Vivo Studies of Phenylalanine Hydroxylase by Phenylalanine Breath Test: Diagnosis of Tetrahydrobiopterin-Responsive Phenylalanine Hydroxylase Deficiency
    Pediatric Research, 2004
    Co-Authors: Yoshiyuki Okano, Kazuhiko Takatori, Masahiro Kajiwara, Yutaka Hase, Mie Kawajiri, Yasuaki Nishi, Koji Inui, Norio Sakai, Yoko Tanaka, Tsunekazu Yamano
    Abstract:

    Tetrahydrobiopterin (BH4)-responsive phenylalanine hydroxylase (PAH) deficiency is characterized by reduction of blood phenylalanine level after a BH4-loading test. Most cases of BH4-responsive PAH deficiency include mild phenylketonuria (PKU) or mild hyperphenylalaninemia (HPA), but not all patients with mild PKU respond to BH4. We performed the phenylalanine breath test as reliable method to determine the BH4 responsiveness. Phenylalanine breath test quantitatively measures the conversion of L-[1-13C] phenylalanine to 13CO2 and is a noninvasive and rapid test. Twenty Japanese patients with HPA were examined with a dose of 10 mg/kg of 13C-phenylalanine with or without a dose of 10 mg . kg(-1) . d(-1) of BH4 for 3 d. The phenylalanine breath test [cumulative recovery rate (CRR)] could distinguish control subjects (15.4 +/- 1.5%); heterozygotes (10.3 +/- 1.0%); and mild HPA (2.74%), mild PKU (1.13 +/- 0.14%), and classical PKU patients (0.29 +/- 0.14%). The genotypes in mild PKU cases were compound heterozygotes with mild (L52S, R241C, R408Q) and severe mutations, whereas a mild HPA case was homozygote of R241C. CRR correlated inversely with pretreatment phenylalanine levels, indicating the gene dosage effects on PKU. BH4 loading increased CRR from 1.13 +/- 0.14 to 2.95 +/- 1.14% (2.6-fold) in mild PKU and from 2.74 to 7.22% (2.6-fold) in mild HPA. A CRR of 5 to 6% reflected maintenance of appropriate serum phenylalanine level. The phenylalanine breath test is useful for the diagnosis of BH4-responsive PAH deficiency and determination of the optimal dosage of BH4 without increasing blood phenylalanine level.

Gert Lubec - One of the best experts on this subject based on the ideXlab platform.

  • The effect of ovariectomy on phenylalanine and tyrosine metabolism.
    Amino Acids, 1994
    Co-Authors: I. Presch, Gert Lubec
    Abstract:

    Although the regulatory activity of steroid hormones on amino acid metabolism has been described, no information is published on the effect of ovariectomy. We studied the influence of ovariectomy in Wistar rats determining the amino acids phenylalanine and tyrosine in liver, kidney, plasma and urine. 32 animals were used in the study, 12 animals were sham operated, 9 animals were ovariectomized and 11 rats were ovariectomized and supplemented with estradiol. No quantitative changes were detected comparing liver and kidney phenylalanine and tyrosine between the groups (sham operated rats liver phenylalanine 2,53nM/mg ± 1,07; liver tyrosine 1.95nM/mg ± 0.92; kidney phenylalanine 2.16nM/mg ± 0.53; kidney tyrosine 1.80nM/mg ± 0.39. Ovariectomized rats showed liver phenylalanine 3.07nM/mg ± 1.14; liver tyrosine 2.63nM/mg ± 1.01; kidney phenylalanine 2.30 nM/mg ± 0.74; kidney tyrosine 1.93nM/mg ± 0.63. Ovariectomized and estradiol supplemented rats presented with liver phenylalanine 2.84nM/mg ± 1.40; liver tyrosine 2.35nM/mg ± 1.28; kidney phenylalanine 1.91nM/mg ± 0.26, kidney tyrosine 1.67nM/mg ± 0.23.). When, however, the phenylalanine/tyrosine ratio in the liver was evaluated, ovariectomized rats showed a significant decrease of the quotient (p = 0.001). The phenylalanine/tyrosine ratio was restored by estradiol replacement. Our findings show that phenylalanine and tyrosine metabolism is under estradiol control. The effect on the metabolic changes could be mediated by enzyme systems as phenylalanine hydroxylase, tyrosine hydroxylase and tyrosine aminotransferase. Our results would be compatible with previous reports on the stimulatory effect of estradiol on these enzymes. The kidney phenylalanine/tyrosine ratio was unaffected by ovariectomy and/or estradiol replacement which can be easily explained by different pools, enzyme activities, filtration/reabsorption effects, etc.

Mariappanadar Vairamani - One of the best experts on this subject based on the ideXlab platform.

  • Halogen-substituted phenylalanines as enantioselective selectors for enantioselective discrimination of amino acids: effect of halogen.
    Rapid communications in mass spectrometry : RCM, 2008
    Co-Authors: Sangeeta Kumari, Suman Prabhakar, Mariappanadar Vairamani
    Abstract:

    Halogen-substituted phenylalanines with a halogen X (X = F, Cl, Br or I) in the para position in the aromatic ring of L-phenylalanine are used as enantioselective selectors to explore the effect of the halogen substituent on the enantioselective discrimination of amino acids. Enantioselective discrimination is achieved by investigating the collision-induced dissociation spectra of the trimeric complex ion, [CuII(ref)2(A)-H]+, generated by electrospraying a solution of a mixture of D- or L-analyte amino acid (A), enantioselective reference ligand (ref) and CuCl2. The relative abundances of fragment ions resulting from the competitive loss of reference and analyte amino acids are considered for measuring the degree of enantioselective discrimination by applying the kinetic method. The enantioselectivity of the p-halogenated derivatives of L-Phe increases from fluorine to iodine for the studied amino acids (except for acidic amino acids). The validity of the present method has also been checked by cross enantioselective experiments using p-iodo-D-Phenylalanine as the reference in place of p-iodo-L-phenylalanine. The enantioselectivity of fluoro-substituted L-phenylalanine is less than that obtained with L-phenylalanine. The high inductive effect of the fluorine atom decreases the strength of the pi-pi stacking interaction. The presence of halogen affects the enantioselectivity by inductive and steric effects.

David J. Owen - One of the best experts on this subject based on the ideXlab platform.

  • Structural basis for binding of accessory proteins by the appendage domain of GGAs
    Nature Structural & Molecular Biology, 2003
    Co-Authors: Brett M. Collins, Margaret S Robinson, Gerrit J. K. Praefcke, David J. Owen
    Abstract:

    The Golgi-associated, γ-adaptin-related, ADP-ribosylation-factor binding proteins (GGAs) and adaptor protein (AP)-1 are adaptors involved in clathrin-mediated transport between the trans -Golgi network and endosomal system. The appendage domains of GGAs and the AP-1 γ-adaptin subunit are structurally homologous and have been proposed to bind to accessory proteins via interaction with short sequences containing phenylalanines and acidic residues. Here we present the structure of the human GGA1 appendage in complex with its cognate binding peptide from the p56 accessory protein (DDDDFGGFEAAETFD) as determined by X-ray crystallography. The interaction is governed predominantly by packing of the first two phenylalanine residues of the peptide with conserved basic and hydrophobic residues from GGA1. Additionally, several main chain hydrogen bonds cause the peptide to form an additional β-strand on the edge of the preexisting β-sheet of the protein. Isothermal titration calorimetry was used to assess the affinities of different peptides for the GGA and γ-appendage domains.

  • Structural basis for binding of accessory proteins by the appendage domain of GGAs.
    Nature structural biology, 2003
    Co-Authors: Brett M. Collins, Margaret S Robinson, Gerrit J. K. Praefcke, David J. Owen
    Abstract:

    The Golgi-associated, gamma-adaptin-related, ADP-ribosylation-factor binding proteins (GGAs) and adaptor protein (AP)-1 are adaptors involved in clathrin-mediated transport between the trans-Golgi network and endosomal system. The appendage domains of GGAs and the AP-1 gamma-adaptin subunit are structurally homologous and have been proposed to bind to accessory proteins via interaction with short sequences containing phenylalanines and acidic residues. Here we present the structure of the human GGA1 appendage in complex with its cognate binding peptide from the p56 accessory protein (DDDDFGGFEAAETFD) as determined by X-ray crystallography. The interaction is governed predominantly by packing of the first two phenylalanine residues of the peptide with conserved basic and hydrophobic residues from GGA1. Additionally, several main chain hydrogen bonds cause the peptide to form an additional beta-strand on the edge of the preexisting beta-sheet of the protein. Isothermal titration calorimetry was used to assess the affinities of different peptides for the GGA and gamma-appendage domains.

Yoshiyuki Okano - One of the best experts on this subject based on the ideXlab platform.

  • Effects of tetrahydrobiopterin and phenylalanine on in vivo human phenylalanine hydroxylase by phenylalanine breath test.
    Molecular Genetics and Metabolism, 2007
    Co-Authors: Yoshiyuki Okano, Kazuhiko Takatori, Satoshi Kudo, Tomoko Sakaguchi, Minoru Asada, Masahiro Kajiwara, Tsunekazu Yamano
    Abstract:

    Abstract BH 4 administration results in the reduction of blood phenylalanine level in patients with tetrahydrobiopterin (BH 4 )-responsive phenylalanine hydroxylase (PAH) deficiency. The mechanism underlying BH 4 response remains unknown. Here, we studied the effects of BH 4 and phenylalanine on in vivo PAH activity of normal controls using the phenylalanine breath test (PBT) by converting l -[1- 13 C] phenylalanine to 13 CO 2 . Phenylalanine oxidation rates were expressed as Δ 13 C ( 13 CO 2 / 12+13 CO 2 , ‰) and cumulative recovery rates over 120 min (CRR 120 , %; total amount of 13 CO 2 /the administered dose of 13 C-phenylalanine). Under physiological conditions of blood phenylalanine, BH 4 administration reduced the Δ 13 C peak from 40.8‰ to 21.6‰ and CRR 120 from 16.9% to 10.2%. Under high blood phenylalanine conditions, administration of BH 4 increased the Δ 13 C peak from 30.7‰ to 46.0‰, while the CRR 120 was similar between phenylalanine (19.9%) and phenylalanine + BH 4 (21.1%) groups. Corrected Δ 13 C and CRR 120 were calculated against serum phenylalanine levels to remove the effects of phenylalanine loading. After BH 4 administration, the corrected Δ 13 C peak increased from 82.7‰ to 112.6‰, while the corrected CRR 120 was similar (47.6% and 45.6%). These results indicate that phenylalanine worked as a regulator of in vivo PAH by serving as both a substrate and an activator for the enzyme. Excessive dosages of BH 4 inhibited PAH under normal phenylalanine conditions and activated PAH under conditions of high phenylalanine. The regulation system is therefore designed to maintain phenylalanine levels in the human body. Appropriate BH 4 supplementation must be reviewed in patients with BH 4 -responsive PAH deficiency.

  • In Vivo Studies of Phenylalanine Hydroxylase by Phenylalanine Breath Test: Diagnosis of Tetrahydrobiopterin-Responsive Phenylalanine Hydroxylase Deficiency
    Pediatric Research, 2004
    Co-Authors: Yoshiyuki Okano, Kazuhiko Takatori, Masahiro Kajiwara, Yutaka Hase, Mie Kawajiri, Yasuaki Nishi, Koji Inui, Norio Sakai, Yoko Tanaka, Tsunekazu Yamano
    Abstract:

    Tetrahydrobiopterin (BH4)-responsive phenylalanine hydroxylase (PAH) deficiency is characterized by reduction of blood phenylalanine level after a BH4-loading test. Most cases of BH4-responsive PAH deficiency include mild phenylketonuria (PKU) or mild hyperphenylalaninemia (HPA), but not all patients with mild PKU respond to BH4. We performed the phenylalanine breath test as reliable method to determine the BH4 responsiveness. Phenylalanine breath test quantitatively measures the conversion of L-[1-13C] phenylalanine to 13CO2 and is a noninvasive and rapid test. Twenty Japanese patients with HPA were examined with a dose of 10 mg/kg of 13C-phenylalanine with or without a dose of 10 mg . kg(-1) . d(-1) of BH4 for 3 d. The phenylalanine breath test [cumulative recovery rate (CRR)] could distinguish control subjects (15.4 +/- 1.5%); heterozygotes (10.3 +/- 1.0%); and mild HPA (2.74%), mild PKU (1.13 +/- 0.14%), and classical PKU patients (0.29 +/- 0.14%). The genotypes in mild PKU cases were compound heterozygotes with mild (L52S, R241C, R408Q) and severe mutations, whereas a mild HPA case was homozygote of R241C. CRR correlated inversely with pretreatment phenylalanine levels, indicating the gene dosage effects on PKU. BH4 loading increased CRR from 1.13 +/- 0.14 to 2.95 +/- 1.14% (2.6-fold) in mild PKU and from 2.74 to 7.22% (2.6-fold) in mild HPA. A CRR of 5 to 6% reflected maintenance of appropriate serum phenylalanine level. The phenylalanine breath test is useful for the diagnosis of BH4-responsive PAH deficiency and determination of the optimal dosage of BH4 without increasing blood phenylalanine level.