Search results for "phenylalanine hydroxylase"
showing 10 items of 17 documents
Phenylalanine hydroxylase from the sponge Geodia cydonium: implication for allorecognition and evolution of aromatic amino acid HYDROXYLASESfn1fn1The…
1998
Abstract The prophenoloxidase activating system is a defense system, frequently reported both in protostomes and in deuterostomes. The final product of the phenoloxidase activity is melanin which is ubiquitously present throughout the metazoan kingdom. The melanin synthesis pathway starts with the amino acid [aa] phenylalanine which is converted to tyrosine by the phenylalanine hydroxylase [PAH]. We show that after allo-transplantation in the marine sponge Geodiacydonium PAH is upregulated in the grafts. Enzyme determination studies revealed that PAH activity increases by three-fold two d after transplantation and reaches its maximum after 3 d (by 3.7-fold). This finding was supported by de…
Somatic copy number alterations are associated with EGFR amplification and shortened survival in patients with primary glioblastoma.
2019
Glioblastoma (GBM) is the most common malignant primary tumor of the central nervous system. With no effective therapy, the prognosis for patients is terrible poor. It is highly heterogeneous and EGFR amplification is its most frequent molecular alteration. In this light, we aimed to examine the genetic heterogeneity of GBM and to correlate it with the clinical characteristics of the patients. For that purpose, we analyzed the status of EGFR and the somatic copy number alterations (CNAs) of a set of tumor suppressor genes and oncogenes. Thus, we found GBMs with high level of EGFR amplification, low level and with no EGFR amplification. Highly amplified tumors showed histological features of…
PAH gene mutations in the Sicilian population: association with minihaplotypes and expression analysis.
2001
Abstract The molecular basis of PAH deficiency in the Sicilian population is characterized by a marked heterogeneity, with 44 mutations at a single locus identified by a "gene-scanning" approach and accounting for a detection rate of 91%. The remaining 9% of PAH alleles does not bear mutations in any of the 13 exons and 24 exon/intron junctions. Three mutations IVS10nt-11 G > A, R261Q, and A300S accounted for 30.5%, whereas the remaining mutations were found at relative frequencies of less than 5% and 20 mutations were observed once only. Five mutations have been detected only in Sicilians so far. By studying the association of mutations with intragenic STR-VNTR haplotypes ("minihaplotypes"…
A methodological strategy for PAH genotyping in populations with a marked molecular heterogeneity of hyperphenylalaninemia.
2001
Abstract The elucidation of the molecular basis of hyperphenylalaninemia in various world populations (PKU Consortium Database: http://www.mcgill.ca/pahdb/) has revealed a remarkable molecular heterogeneity at the locus encoding for phenylalanine hydroxylase. As a consequence, genotyping of HPA patients has prompted the establishment of an impressive number of mutation detection protocols. In spite of the large variety of methods proposed so far, no comprehensive strategy has been yet developed for the detection of PAH gene mutations. Therefore, new approaches, combining the advantages of individual methods are required, especially in populations with a high number of PAH gene mutations. In…
Maternal phenylketonuria in two Sicilian families identified by maternal blood phenylalanine level screening and identification of a new phenylalanin…
1999
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Structure of the phenylalanine hydroxylase gene in Drosophila melanogaster and evidence of alternative promoter usage.
1996
The complete Drosophila melanogaster phenylalanine hydroxylase gene isolated from a genomic library was sequenced. Gene structure consisted of five exons covering a region of around 3 kb. Position of introns in the C-terminal domain was conserved with mammalian aromatic amino acid hydroxylase genes. Putative promoter sequences in the 5'UTR and intron 1 were identified. A novel transcript was detected differing from that previously reported by the inclusion of a part of the intron 1 sequence. It could be produced using an alternative promoter. The deduced open reading frame would code a protein with a small difference at the N-terminus. Expression of the alternative transcripts was examined …
In Silico Analysis of the Novel Variant Q375R in the Phenylalanine Hydroxylase Gene
2019
Background: Phenylketonuria is an inborn metabolic disorder inherited in an autosomal recessive pattern. The detection of pathogenic variations improves the power of at-risk carrier and prenatal detection. We previously found Q375R a novel phenylalanine hydroxylase variation in phenylketonuria patients from the south-west of Iran. Objectives: Here, we aimed to evaluate the rate of the pathogenicity of this novel variant and three other intron variants (IVS9 + 32insA, IVS11 + 163delC, and IVS12 + 30C>T). Methods: The pathogenicity and some structural features of Q375R were analyzed using bioinformatics tools including SIFT, PolyPhen, Mutpred, MutationTaster, nSSNP Analyzer, SNP effect, 3DLig…
Candidate target mechanisms of the growth inhibitor cyromazine: Studies of phenylalanine hydroxylase, puparial amino acids, and dihydrofolate reducta…
2000
Cyromazine, an insect growth regulator, affects larval and pupal cuticles in dipterans and some other insects. The mode of action of this aminotriazine is not known yet, though it has been shown not to inhibit the synthesis of chitin and cuticular proteins. Cyromazine may, however, act on some step(s) of sclerotization of the cuticle. In the present study, we have analyzed the key enzyme for the production of sclerotization agents, phenylalanine hydroxylase (PAH), using the enzyme from Drosophila, a cyromazine-sensitive insect. PAH was studied in vitro with cyromazine and three biologically less active derivatives at concentrations ranging from 1 μM to 1 mM. None of the compounds did signif…
Reduced Cerebral Fluoro-l-Dopamine Uptake in Adult Patients Suffering from Phenylketonuria
2007
Deficiency of phenylalanine hydroxylase activity in phenylketonuria (PKU) causes an excess of phenylalanine (Phe) throughout the body, predicting impaired synthesis of catecholamines in the brain. To test this hypothesis, we used positron emission tomography (PET) to measure the utilization of 6-[18F]fluoro-l-dopamine (FDOPA) in the brain of adult patients suffering from PKU and in healthy controls. Dynamic 2-h long FDOPA emission recordings were obtained in seven adult PKU patients (five females, two males; age: 21 to 27 years) with elevated serum Phe levels, but lacking neurologic deficits. Seven age-matched, healthy volunteers were imaged under identical conditions. The utilization of F…
Phenylalanine Hydroxylase Participation in the Synthesis of Serotonin and Pteridines in Drosophila melanogaster
1997
Abstract Phenylalanine hydroxylase is involved in the synthesis of serotonin and pteridines, probably catalysing the hydroxylation of tryptophan and a tetrahydropterin oxidase reaction, respectively. Supplementation of the wild-type Drosophila diet with either L-Phe or L-Trp induced a significant increase in the phenylalanine hydroxylase concentration, while L-Tyr supplementation had no effect. The level of serotonin in adult heads of the PAH-defective mutant Henna recessive-3 was significantly lower than that obtained for the wild-type strain. A 4-fold increase in the concentration of phenylalanine hydroxylase is observed during the pharate adult head development. It occurs in parallel wit…