The aim of the presented study was to assess the effect of a single administration of Fe3+-dextran on immune cell counts and pterin biomolecule production as novel sensors of the piglets immune system activation, and to determine concentrations of cortisol, a traditional hormonal biosensor of the stress response. Pterins (neopterin and biopterin) in the piglets blood serum were analyzed by separation using reversed-phase HPLC. A single dose of Fe3+-dextran produced a special stress situation in the piglets organism which manifested itself by an increased production of neopterin (p | 0.05) and biopterin (p | 0.01) in the experimental piglets. Changes in cortisol concentrations and leukocyte counts were influenced by handling stress and were not specifically correlated to iron dextran application. Iron concentrations in the internal environment of the experimental piglets group were higher by an order of magnitude compared with the controls, and the highest serum concentrations of iron (p | 0.01) were
Pterins as Sensors of Response to the Application of Fe3 -Dextran in Piglets. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
Principal Investigator:YAMAMOTO Hiroshi, Project Period (FY):1995 - 1997, Research Category:Grant-in-Aid for international Scientific Research, Section:University-to-University Cooperative Research, Research Field:物質変換
1DWV: Structures of the N(Omega)-Hydroxy-L-Arginine Complex of Inducible Nitric Oxide Synthase Oxygenase Dimer with Active Andinactive Pterins
1DWV: Structures of the N(Omega)-Hydroxy-L-Arginine Complex of Inducible Nitric Oxide Synthase Oxygenase Dimer with Active Andinactive Pterins
I demarcate real-time scheduling as dy- namic scheduling, making decisions based on latest suited materials instead of using predefined or pre-calculated values Cardiorespiratory and electroencephalographic responses to maximum sensitive material concern in people with mortal lobe epilepsy Antimicrob Agents Chemother 49:5160-5161 Beck JT, Ullman B (1990) Nutritional requirements of wild-type and folate transport-deficient Leishmania donovani an eye to pterins and folates Some of the defects may follow-up in significant hypoxemia, the sequelae of which cover clubbing, polycythemia, wield xenophobia, hypercyanotic spells, brain abscess, and cerebrovascular chance (Fulton, 2008) ,a href=http://cvyp-ltd.com/professional-experience/chapter33/part1/,abilify 15mg on-line,/a,. Make sure of the fractions of the elution in harmony pro the self-assurance of HSP by SDS-PAGE and Western blotting ,,3, 24] In distinction, we developed a one-step affinity-chromatography purification formality after the ...
Do You Have Hyperphenilalaninemia Due To Pterin-4-alpha-carbin? Join friendly people sharing true stories in the I Have Hyperphenilalaninemia Due to Pterin-4-alpha-carbin group. Find support forums, advice and chat with groups who share this life exp...
A recently described new form of hyperphenylalaninemia is characterized by the excretion of 7-substituted isomers of biopterin and neopterin and 7-oxo-biopterin in the urine of patients. It has been shown that the 7-substituted isomers of biopterin and neopterin derive from L-tetrahydrobiopterin and D-tetrahydroneopterin and are formed during hydroxylation of phenylalanine to tyrosine with rat liver dehydratase-free phenylalanine hydroxylase.,br /,We have now obtained identical results using human phenylalanine hydroxylase. The identity of the pterin formed in vitro and derived from L-tetrahydrobiopterin as 7-(1,2-dihydroxypropyl)pterin was proven by gas-chromatography mass spectrometry. Tetrahydroneopterin and 6-hydroxymethyltetrahydropterin also are converted to their corresponding 7-substituted isomers and serve as cofactors in the phenylalanine hydroxylase reaction. Dihydroneopterin is converted by dihydrofolate reductase to the tetrahydro form which is biologically active as a cofactor ...
SPR Deficiency is caused by mutations in the SPR gene. The SPR gene provides instructions for making the enzyme sepiapterin reductase. Specifically, sepiapterin reductase is responsible for the last step in the production of tetrahydrobiopterin. Most SPR gene mutations result in an enzyme with little or no function.. A nonfunctional sepiapterin reductase gene leads to a lack of tetrahydrobiopterin which causes a disruption in neurotransmitter metabolism. SPR Deficiency is due to an autosomal recessive inheritance. In this type of inheritance pattern there are two mutated copies of the gene that causes the disorder. A person with SPR deficiency usually has unaffected parents (no symptoms) who each carry a single copy of the mutated gene and are referred to as carriers.. Autosomal recessive disorders are typically not seen in every generation of an affected family. When two people who are carriers of an autosomal recessive condition have a child, there is a 25% (1 in 4) chance that the child will ...
This is the first study to examine the effect of increased intracellular levels of tetrahydrobiopterin on endothelial function in isolated arteries. As an experimental model, we used canine middle cerebral arteries incubated with sepiapterin. The major new findings are that (1) sepiapterin stimulates tetrahydrobiopterin production in endothelial and smooth muscle cells of intact arteries and (2) high tissue levels of tetrahydrobiopterin have an inhibitory effect on endothelium-dependent relaxations, whereas (3) in the presence of superoxide dismutase, tetrahydrobiopterin augments endothelium-dependent relaxations.. Under basal conditions, measurements of tetrahydrobiopterin levels revealed a detectable amount of NO synthase cofactor in cerebral arterial wall preparations incubated for 24 hours. Similar levels were also detected in freshly isolated basilar arteries,16 suggesting that tetrahydrobiopterin production had not been affected by incubation in MEM. The removal of endothelial cells caused ...
TY - JOUR. T1 - A Flexible Loop in Tyrosine Hydroxylase Controls Coupling of Amino Acid Hydroxylation to Tetrahydropterin Oxidation. AU - Colette Daubner, S.. AU - McGinnis, James Thomas. AU - Gardner, Meredith. AU - Kroboth, Stacie L.. AU - Morris, Adam R.. AU - Fitzpatrick, Paul F. PY - 2006/6/2. Y1 - 2006/6/2. N2 - The role of a polypeptide loop in tyrosine hydroxylase (TyrH) whose homolog in phenylalanine hydroxylase (PheH) takes on a different conformation when substrates are bound has been studied using site-directed mutagenesis. The loop spans positions 177 to 191; alanine was introduced into those positions, introducing one alanine substitution per TyrH variant. Mutagenesis of residues in the center of the loop resulted in alterations in the KM values for substrates, the Vmax value for dihydroxyphenylalanine (DOPA) synthesis, and the coupling of tetrahydropterin oxidation to tyrosine hydroxylation. The variant with the most altered KM value for 6-methyltetrahydropterin was TyrH F184A. ...
Cabelli, D.E., Guan, Y., Leveque, V., Hearn, A.S., Tainer, J.A., Nick, H.S., Silverman, D.N. Role of tryptophan 161 in catalysis by human manganese superoxide dismutase. Biochemistry 38:11686, 1999. Crane, B.R., Arvai, A.S., Ghosh, D.K., Getzoff, E.D., Stuehr, D.J., Tainer, J.A. Structures of the Nw-hydroxy-L-arginine complex of inducible nitric oxide synthase dimer with active and inactive pterins. Biochemistry 39:4608, 2000. Crane, B.R., Rosenfield, R.A., Arvai, A.S., Ghosh, D.K., Tainer, J.A., Stuehr, D.J., Getzoff, E.D. N-terminal domain swapping and metal ion binding in nitric oxide synthase dimerization. EMBO J. 18:6271, 1999. Daniels, D.S., Mol, C.D., Arvai, A.S., Kanugula, S., Pegg, A.E., Tainer J.A. Active and alkylated human AGT structures: A novel zinc site, inhibitor, and extrahelical base binding. EMBO J. 19:1719, 2000. Daniels, D.S., Tainer, J.A. Conserved structural motifs governing the stoichiometric repair of alkylated DNA by O(6)-alkylguanine-DNA alkyltransferase. Mutat. Res. ...
TY - JOUR. T1 - Phenylalanine Hydroxylase. T2 - Structural Determination of the Tetrahydropterin Intermediates by 13C NMR Spectroscopy. AU - Lazarus, Robert A.. AU - DeBrosse, Charles W.. AU - Benkovic, Stephen J.. PY - 1982/1/1. Y1 - 1982/1/1. UR - http://www.scopus.com/inward/record.url?scp=0001447533&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=0001447533&partnerID=8YFLogxK. U2 - 10.1021/ja00388a105. DO - 10.1021/ja00388a105. M3 - Article. AN - SCOPUS:0001447533. VL - 104. SP - 6869. EP - 6871. JO - Journal of the American Chemical Society. JF - Journal of the American Chemical Society. SN - 0002-7863. IS - 24. ER - ...
TY - JOUR. T1 - Reduction and oxidation of the active site iron in tyrosine hydroxylase. T2 - Kinetics and specificity. AU - Frantom, Patrick A.. AU - Seravalli, Javier. AU - Ragsdale, Stephen W.. AU - Fitzpatrick, Paul F.. PY - 2006/2/21. Y1 - 2006/2/21. N2 - Tyrosine hydroxylase (TyrH) is a pterin-dependent enzyme that catalyzes the hydroxylation of tyrosine to form dihydroxyphenylalanine. The oxidation state of the active site iron atom plays a central role in the regulation of the enzyme. The kinetics of reduction of ferric TyrH by several reductants were determined by anaerobic stopped-flow spectroscopy. Anaerobic rapid freeze-quench EPR confirmed that the change in the near-UV absorbance of TyrH upon adding reductant corresponded to iron reduction. Tetrahydrobiopterin reduces wild-type TyrH following a simple second-order mechanism with a rate constant of 2.8 ± 0.1 mM-1 s-1. 6-Methyltetrahydropterin reduces the ferric enzyme with a second-order rate constant of 6.1 ± 0.1 mM -1 s-1 and ...
Inadequate tetrahydrobiopterin (BH4) concentration has been linked to impaired endothelial NO synthase (eNOS) activity and to loss of endothelial function in vascular conditions such as hypercholesterolemia. Blau and Thöny correctly contend that despite the critical importance of BH4 in NO formation from eNOS, patients with BH4 deficiency typically show no evidence of vascular disease. Studies that have evaluated the effects of BH4 supplementation have further observed divergent effects in animal models as well as in humans, with some studies reporting beneficial or no effects and a few reporting actual worsening of vascular function.1 We have recently presented an alternative hypothesis that may reconcile these apparently contradictory findings. This is that the relative concentrations of fully reduced (BH4) and oxidized forms of tetrahydrobiopterin (BH2), rather than the absolute concentration of BH4, are what governs the nature of products generated from eNOS.2 At low BH4 or high BH2 ...
Mono- and Stereopictres of 5.0 Angstrom coordination sphere of Magnesium atom in PDB 3ilo: Crystal Structure of E. Coli Hppk(D97A) in Complex With Mgampcpp and 6-Hydroxymethyl-7,8-Dihydropterin
SPR antibody [N2C3] (sepiapterin reductase (7,8-dihydrobiopterin:NADP+ oxidoreductase)) for ICC/IF, IHC-P, IP, WB. Anti-SPR pAb (GTX113552) is tested in Human, Mouse samples. 100% Ab-Assurance.
Complete information for PTS gene (Protein Coding), 6-Pyruvoyltetrahydropterin Synthase, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Thank you for your interest in spreading the word about Biochemical Society Transactions.. NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.. ...
The SCOP classification for the Formylmethanofuran:tetrahydromethanopterin formyltransferase superfamily including the families contained in it. Additional information provided includes InterPro annotation (if available), Functional annotation, and SUPERFAMILY links to genome assignments, alignments, domain combinations, taxonomic visualisation and hidden Markov model information.
ESWL is an effective, non-invasive therapy utilized to fragment stones in the kidney and subsequently be cleared in the urinary tract. Although lithotripsy provides a safer alternative to invasive treatments for removing stones, ESWL may cause vasoconstriction after ESWL treatment, reducing renal blood flow, which can cause kidney damage leading to acute to chronic hypertension clinically. This may be due to kidney vascular endothelial dysfunction, which is characterized as increased oxidative stress and decreased endothelial nitric oxide synthase (eNOS)-derived nitric oxide (NO) bioavailability. We hypothesized that ESWL would decrease NO and increase hydrogen peroxide (H2O2) in rat renal veins. Rats given tetrahydrobiopterin (BH4), the essential cofactor of eNOS coupling, would cause a decrease in H2O2 release and increase in NO release compared to ESWL + saline controls. On the contrary, when dihydrobiopterin (BH2), the cofactor for eNOS uncoupling, is given at the end of ESWL treatment we predict an
The PND association is a disease organization representing children and families who are affected by a pediatric neurotransmitter disease.. As a rare disease advocacy organization our mission is to represent and be a voice for all children affected by dopamine related PNDs. Our goals are to help children and families who are affected by PNDs, support the identification of new PNDs, find better treatments and ultimately a cure for those diseases that are already known. The PND Association was founded in 1998 and is a non-profit, voluntary organization.. All information contained on the PND Association website is intended for informational and educational purposes. The information is not intended to be a replacement or substitute for professional medical treatment or for professional medical advice relative to a specific medical question or condition. ...
Dihydrobiopterin (BH2) is a pteridine compound produced in the synthesis of L-DOPA, dopamine, norepinephrine and epinephrine. It is restored to the required cofactor tetrahydrobiopterin by dihydrobiopterin reductase. Pteridine ...
1. It has previously been shown that folate polyglutamates in the rat are catabolized almost exclusively via cleavage of the C-9-N-10 bond, resulting in the formation of pteridines and p-aminobenzoylglutamate. The latter catabolite is rapidly excreted, appearing in the urine as acetamidobenzoylglutamate and is undetectable in rat liver.. 2. The pteridines catabolites on the other hand are retained to a much greater extent by the liver, forming an ever-increasing proportion of the retained radioactive tracer.. 3. A possible role for these pteridines as cofactors in brain metabolism is discussed.. ...
TY - JOUR. T1 - C-terminus of heat shock protein 70-interacting protein-dependent GTP cyclohydrolase I degradation in lambs with increased pulmonary blood flow. AU - Sun, Xutong. AU - Fratz, Sohrab. AU - Sharma, Shruti. AU - Hou, Yali. AU - Rafikov, Ruslan. AU - Kumar, Sanjiv. AU - Rehmani, Imran. AU - Tian, Jing. AU - Smith, Anita. AU - Schreiber, Christian. AU - Reiser, Judith. AU - Naumann, Susanne. AU - Haag, Sebastian. AU - Hess, John. AU - Catravas, John D.. AU - Patterson, Cam. AU - Fineman, Jeffery R.. AU - Black, Stephen M.. PY - 2011/7/1. Y1 - 2011/7/1. N2 - We showed that nitric oxide (NO) signaling is decreased in the pulmonary vasculature before the development of endothelial dysfunction in a lamb model of congenital heart disease and increased pulmonary blood flow (Shunt). The elucidation of the molecular mechanism by which this occurs was the purpose of this study. Here, we demonstrate that concentrations of the endogenous NO synthase (NOS) inhibitor, asymmetric dimethylarginine ...
Jones, C.L., Vasquez-Vivar, J., Kalyanaraman, B., Griscavage-Ennis, J.M., Gross, S.S. and Smith, C.L. 2002. The redox status of bound pterin cofactor determines whether eNOS produces NO or superoxide anion: [3H] - BH4 binding studies provide insights into vascular pathophysiology. in: Milstien, S., Kapatos, G., Levine, R.A. and Shane, B. (ed.) Chemistry and biology of pteridines and folates: proceedings of the 12th International Symposium on Pteridines and Folates, National Institutes of Health, Bethesda, M.D. Boston, USA Kluwer Academic Publishers. pp. 271-276 Characterization of CXC and CC chemokine expression in a murine model of chronic granuloma ...
6-Pyruvoyltetrahydropterin synthase deficiency is an autosomal recessive disorder that causes malignant hyperphenylalaninemia due to tetrahydrobiopterin deficiency. It belongs to the rare diseases. It is a recessive disorder that is accompanied by hyperphenylalaninemia. Commonly reported symptoms are initial truncal hypotonia, subsequent appendicular hypertonia, bradykinesia, cogwheel rigidity, generalized dystonia, and marked diurnal fluctuation. Other reported clinical features include difficulty in swallowing, oculogyric crises, somnolence, irritability, hyperthermia, and seizures. Chorea, athetosis, hypersalivation, rash with eczema, and sudden death have also been reported. Patients with mild phenotypes may deteriorate if given folate antagonists such as methotrexate, which can interfere with a salvage pathway through which dihydrobiopterin is converted into tetrahydrobiopterin via dihydrofolate reductase. Treatment options include substitution with neurotransmitter precursors (levodopa, ...
TY - JOUR. T1 - Effect of tetrahydrobiopterin on selective endothelial dysfunction of epicardial porcine coronary arteries induced by cardiopulmonary bypass. AU - Stevens, Louis Mathieu. AU - Fortier, Simon. AU - Aubin, Marie Claude. AU - El-Hamamsy, Ismail. AU - Maltais, Simon. AU - Carrier, Michel. AU - Perrault, Louis P.. PY - 2006/9/1. Y1 - 2006/9/1. N2 - Background: We hypothesized that cardiopulmonary bypass induces a selective alteration of the coronary arterial endothelial cell signal transduction which could be explained by a state of depletion and/or decreased activity of endogenous tetrahydrobiopterin (BH4). The aim of this study was to assess the effects of cardiopulmonary bypass and BH4 on the endothelial function of epicardial coronary arteries in a swine model of cardiopulmonary bypass. Methods: Swine underwent 90 min of cardiopulmonary bypass alone (N = 19) or in association with a brief cardioplegic arrest with (N = 6) or without (N = 5) in vivo BH4 administration, followed by a ...
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Tyrosine hydroxylase was separated from polyphenol oxidase activity and was highly purified from betacyanin producing callus cultures of Portulaca grandiflora. The purified enzyme catalyzed the formation of DOPA (l-3,4-dihydroxyphenylalanine) from tyrosine and required the pterin compounds (6-methyl-5,6,7,8-tetrahydropterin; 5,6,7,8-tetrahydrobiopterin; 6,7-dimethyl-5,6,7,8-tetrahydropterin) as coenzyme. The Km values for tyrosine and 6-methyl-5,6,7,8-tetrahydropterin were 0.5 mM and 0.15 mM, respectively. This enzyme was activated by Fe2+ and Mn2+, and inhibited by metal chelating agents.. ...
Tetrahydrobiopterin (BH4) is an essential cofactor for endothelial nitric oxide synthase (eNOS) function and nitric oxide (NO) generation. Augmentation of BH4 levels can prevent eNOS uncoupling and improve endothelial dysfunction in vascular disease states. However, the physiological requirement for de-novo endothelial cell BH4 biosynthesis in eNOS function remains unclear. We generated a novel mouse model with endothelial cell-specific deletion of GCH1, encoding GTP cyclohydrolase 1, an essential enzyme for BH4 biosynthesis, to test the cell-autonomous requirement for endothelial BH4 biosynthesis in vivo.. Mice with a floxed GCH1 allele (GCH1fl/fl) were crossed with Tie2cre mice to delete GCH1 in endothelial cells. GCH1fl/flTie2cre mice demonstrated virtually absent NO bioactivity and significantly greater O2•- production. GCH1fl/flTie2cre aortas and mesenteric arteries had enhanced vasoconstriction to phenylephrine and impaired endothelium-dependent vasodilatations to acetylcholine and ...
B Chronic oral tetrahydrobiopterin treatment in patients with coronary artery disease elevates total biopterin levels but does not improve biopterin redox status or vascular function: a randomised placebo-controlled trial ...
Endothelial dysfunction in vascular disease states is associated with reduced NO bioactivity and increased superoxide (O2 ) production. Some data suggest that an important mechanism underlying endothelial dysfunction is endothelial NO synthase (eNOS) uncoupling, whereby eNOS generates O2 rather than NO, possibly because of a mismatch between eNOS protein and its cofactor tetrahydrobiopterin (BH4). However, the mechanistic relationship between BH4 availability and eNOS coupling in vivo remains undefined because no studies have investigated the regulation of eNOS by BH4 in the absence of vascular disease states that cause pathological oxidative stress through multiple mechanisms. We investigated the stoichiometry of BH4-eNOS interactions in vivo by crossing endothelialtargeted eNOS transgenic (eNOS-Tg) mice with mice overexpressing endothelial GTP cyclohydrolase 1 (GCH-Tg), the rate-limiting enzyme in BH4 synthesis. eNOS protein was increased 8-fold in eNOS-Tg and eNOS/GCH-Tg mice compared with wild type.
p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.,/p> ,p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.,/p> ,p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).,/p> ,p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x,sup>64,/sup> + x,sup>4,/sup> + x,sup>3,/sup> + x + 1. The algorithm is described in the ISO 3309 standard. ,/p> ,p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.,br /> ,strong>Cyclic redundancy and other checksums,/strong>,br /> ,a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993),/a>),/p> Checksum:i ...
Biopterin is a coenzyme thats used to make several important neurotransmitters in the body. Problems with biopterin levels can...
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Semantic Scholar extracted view of The production of meta-tritiotyrosine from p-tritiophenylalanine by phenylalanine hydroxylase. by Gordon Guroff et al.
DOPA responsive dystonia (DRD) and sepiapterin reductase (SR) deficiency are inherited disorders of tetrahydrobiopterin (BH4) metabolism characterized by the signs and symptoms related to monoamine neurotransmitter deficiency. In contrast to classical forms of BH4 deficiency DRD and SR deficiency present without hyperphenylalaninemia and thus cannot be detected by the neonatal screening for phenylketonuria (PKU). While DRD is mostly caused by autosomal dominant mutations in the GTP cyclohydrolase I gene (GCH1), SR deficiency is an autosomal recessive disease. The most important biochemical investigations for the diagnosis of these neurological diseases includes CSF investigations for neurotransmitter metabolites and pterins as well as neopterin and biopterin production in cytokine-stimulated fibroblasts. Discovery of SR deficiency opened new insights into alternative pathways of the cofactor BH4 via carbonyl, aldose, and dihydrofolate reductases. As a consequence of the low dihydrofola
Tetrahydrobiopterin (BH4) cofactor is essential for various processes, and is present in probably every cell or tissue of higher organisms. BH4 is required for various enzyme activities, and for less defined functions at the cellular level. The pathway for the de novo biosynthesis of BH4 from GTP involves GTP cyclohydrolase I, 6-pyruvoyl-tetrahydropterin synthase and sepiapterin reductase. Cofactor regeneration requires pterin-4a-carbinolamine dehydratase and dihydropteridine reductase. Based on gene cloning, recombinant expression, mutagenesis studies, structural analysis of crystals and NMR studies, reaction mechanisms for the biosynthetic and recycling enzymes were proposed. With regard to the regulation of cofactor biosynthesis, the major controlling point is GTP cyclohydrolase I, the expression of which may be under the control of cytokine induction. In the liver at least, activity is inhibited by BH4, but stimulated by phenylalanine through the GTP cyclohydrolase I feedback regulatory ...
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In the present report, the regulation of mRNA abundance and specific activity of PTPS, the second enzyme in the synthesis of BH4, by inflammatory cytokines is described for the first time. GTPCH, the first enzyme in the BH4 synthesis pathway, has been widely described as the rate-limiting step in mammals.9 Up to a 40-fold regulation of GTPCH activity was found in cells treated with inflammatory stimuli,2 8 which is consistent with the strongly elevated GTPCH mRNA level reported in the present article. In humans, PTPS was generally believed to be constitutively present and to become rate limiting on induction of GTPCH, reflected by production of higher neopterin than biopterin concentrations.8 However, the persistent low levels of neopterin in HUVECs even after inflammatory activation (Table⇑), suggest that PTPS is either present with high constitutive activity or that its expression is upregulated by cytokines. We demonstrated that PTPS is upregulated in HUVECs by a combination of inflammatory ...
TY - JOUR. T1 - Phenylalanine binding is linked to dimerization of the regulatory domain of phenylalanine hydroxylase. AU - Zhang, Shengnan. AU - Roberts, Kenneth M.. AU - Fitzpatrick, Paul F.. PY - 2014/10/28. Y1 - 2014/10/28. N2 - Analytical ultracentrifugation has been used to analyze the oligomeric structure of the isolated regulatory domain of phenylalanine hydroxylase. The protein exhibits a monomer-dimer equilibrium with a dissociation constant of ∼46 μM; this value is unaffected by the removal of the 24 N-terminal residues or by phosphorylation of Ser16. In contrast, phenylalanine binding (Kd = 8 μM) stabilizes the dimer. These results suggest that dimerization of the regulatory domain of phenylalanine hydroxylase is linked to allosteric activation of the enzyme.. AB - Analytical ultracentrifugation has been used to analyze the oligomeric structure of the isolated regulatory domain of phenylalanine hydroxylase. The protein exhibits a monomer-dimer equilibrium with a dissociation ...
Methylobacterium extorquens AM1 has been considered as a potential platform strain for industrial production of valuable chemicals such as mevalonate, 1-butanol and 2-hydroxyisobutyrate [30, 32, 33, 41]. In this work, we first optimized a 3-HP synthetic pathway in M. extorquens AM1, and then focused on the demonstration of the mechanism of 3-HP reassimilation.. It has been reported that tuning of gene expression levels was critical for proper functioning of a heterologous synthetic pathway in M. extorquens AM1. For instance, Hu et al. found that the strain expressing the adhE2 and ter from a promoter of intermediate strength produced the highest 1-butanol [32]. In our case, four different promoter strengths were tested and the strongest promoter mxaF was shown to generate the highest 3-HP, comparable with the preliminary titer of other engineered microorganisms [5]. The pool size of precursor acetyl-CoA was similar between the YHP5 strains and the other three recombinant strains, implying that ...
Tetrahydrobiopterin (BH4) is an essential cofactor for eNOS. Sepiapterin (Sep) is converted into BH4 by the salvage pathway. BH4 is labile at physiological pH and easily oxidized to BH3 or BH2, making it useless as a cofactor for eNOS dependent •NO generation. Loss of BH4, whether through increased oxidation or impaired synthesis, has been linked to pulmonary hypertension. Previously we showed that NADPH oxidase derived superoxide (O2•−) impaired angiogenesis of Pulmonary Artery Endothelial Cells (PAEC) isolated from in utero pulmonary hypertension fetal lambs (HTFL). As increased NADPH oxidase activity has been linked to oxidation of BH4 and in turn, impaired eNOS activity, we hypothesized that restoring BH4 with Sep might improve PAEC function isolated from HTFL. To test this hypothesis we supplemented PAEC isolated from normotensive fetal lambs and HTFL with Sep (30 μM) and then examined its effects on angiogenesis. Angiogenesis was quantified with respect to tube length, cell ...
Methylotrophy describes the ability of organisms to grow on reduced organic compounds without carbon-carbon bonds. Methylobacterium extorquens AM1 is capable of growth on one-carbon compounds such as methanol. Methanol is oxidized to formaldehyde which is then used metabolically to generate either energy or biomass. These bacteria are commonly found in the environment, especially associated with plants which produce methanol when metabolizing pectin during cell wall synthesis. The 6.88 Mb genome of strain AM1 comprises a 5.51 Mb chromosome, a 1.26 Mb megaplasmid and three plasmids. [Vuilleumier 2009]. ...
Tetrahydrobiopterin (BH4) is an essential co-factor for NO production from NOS enzymes. When BH4 levels become limiting these enzymes can become un-coupled, leading to superoxide production. GTP cyclohydrolase I (GTPCH), encoded by GCH1, is an essential enzyme in the biosynthesis of BH4. BH4 deficiency has been been shown to cause endothelial dysfunction and to exacerbate atherosclerosis in experimental models. However, the role of BH4 in regulating iNOS activity in leukocytes, and the potential impact of this on atherosclerosis is less clear. We have utilised a novel transgenic mouse to address the role of BH4 and iNOS in macrophage biology.. We designed mice harbouring a floxed portion of the GCH1 locus within the active site of the enzyme (GCHfl/fl mice). We crossed these with mice expressing the cre enzyme under control of the Tie2 promoter (GCHfl/fl Tie2cre). Cre expression causes efficient excision of the floxed allele in all leukocytes and endothelial cells, as detected by PCR for the ...
TY - JOUR. T1 - Acute Tetrahydrobiopterin Improves Endothelial Function in Patients With COPD. AU - Rodriguez-Miguelez, Paula. AU - Gregg, Justin. AU - Seigler, Nichole. AU - Bass, Leon. AU - Thomas, Jeffrey. AU - Pollock, Jennifer S.. AU - Sullivan, Jennifer C. AU - Dillard, Thomas A. AU - Harris, Ryan A.. PY - 2018/9/1. Y1 - 2018/9/1. N2 - Background: Cardiovascular diseases represent a hallmark characteristic in COPD, and endothelial dysfunction has been observed in these patients. Tetrahydrobiopterin (BH4) is an essential cofactor for nitric oxide (NO) synthesis and a regulator of endothelial function. The goal of this study was to test the hypothesis that a single dose of BH4 would improve endothelial function in patients with COPD via an increase in NO bioavailability. Methods: Seventeen patients with COPD completed a randomized, double-blind, placebo (PLC)-controlled, crossover trial with an acute dose of either BH4 (Kuvan; BioMarin Pharmaceutical Inc) or PLC. Flow-mediated dilation ...
Affiliation:Fujita Health University,医学部,准教授, Research Field:General pharmacology,Pathological medical chemistry,Neuroscience in general,Pathological medical chemistry,Neurochemistry/Neuropharmacology, Keywords:テトラヒドロビオプテリン,チロシン水酸化酵素,ドパミン神経,tyrosine hydroxylase,6-ピルボイルテトラヒドロプテリン合成酵素,dopaminergic neuron,6-pyruvoyltetrahydropterin synthase,ノックアウトマウス,Cre-loxP,一酸化窒素, # of Research Projects:10, # of Research Products:33, Ongoing Project:テトラヒドロビオプテリン欠損がもたらす不安定高血圧症とPriapism
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