Phagocytes: Cells that can carry out the process of PHAGOCYTOSIS.Nitric Oxide Synthase: An NADPH-dependent enzyme that catalyzes the conversion of L-ARGININE and OXYGEN to produce CITRULLINE and NITRIC OXIDE.Nitric Oxide Synthase Type II: A CALCIUM-independent subtype of nitric oxide synthase that may play a role in immune function. It is an inducible enzyme whose expression is transcriptionally regulated by a variety of CYTOKINES.Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles.Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.Macrophages: The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)Biopterin: A natural product that has been considered as a growth factor for some insects.Hydro-Lyases: Enzymes that catalyze the breakage of a carbon-oxygen bond leading to unsaturated products via the removal of water. EC 4.2.1.Phenylalanine Hydroxylase: An enzyme of the oxidoreductase class that catalyzes the formation of L-TYROSINE, dihydrobiopterin, and water from L-PHENYLALANINE, tetrahydrobiopterin, and oxygen. Deficiency of this enzyme may cause PHENYLKETONURIAS and PHENYLKETONURIA, MATERNAL. EC 1.14.16.1.Phenylketonurias: A group of autosomal recessive disorders marked by a deficiency of the hepatic enzyme PHENYLALANINE HYDROXYLASE or less frequently by reduced activity of DIHYDROPTERIDINE REDUCTASE (i.e., atypical phenylketonuria). Classical phenylketonuria is caused by a severe deficiency of phenylalanine hydroxylase and presents in infancy with developmental delay; SEIZURES; skin HYPOPIGMENTATION; ECZEMA; and demyelination in the central nervous system. (From Adams et al., Principles of Neurology, 6th ed, p952).Metabolism, Inborn Errors: Errors in metabolic processes resulting from inborn genetic mutations that are inherited or acquired in utero.Pterins: Compounds based on 2-amino-4-hydroxypteridine.Carbon-Nitrogen Ligases with Glutamine as Amide-N-Donor: Enzymes that catalyze the joining of glutamine-derived ammonia and another molecule. The linkage is in the form of a carbon-nitrogen bond. EC 6.3.5.Phenylalanine: An essential aromatic amino acid that is a precursor of MELANIN; DOPAMINE; noradrenalin (NOREPINEPHRINE), and THYROXINE.Nitric Oxide Synthase Type III: A CALCIUM-dependent, constitutively-expressed form of nitric oxide synthase found primarily in ENDOTHELIAL CELLS.Epichlorohydrin: A chlorinated epoxy compound used as an industrial solvent. It is a strong skin irritant and carcinogen.Hypoglycemic Agents: Substances which lower blood glucose levels.Blood Glucose: Glucose in blood.Insulin: A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).Insulin Resistance: Diminished effectiveness of INSULIN in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent HYPERGLYCEMIA or KETOSIS.Resins, Synthetic: Polymers of high molecular weight which at some stage are capable of being molded and then harden to form useful components.Aflatoxin M1: A 4-hydroxylated metabolite of AFLATOXIN B1, one of the MYCOTOXINS from ASPERGILLUS tainted food. It is associated with LIVER damage and cancer resulting from its P450 activation to the epoxide which alkylates DNA. Toxicity depends on the balance of liver enzymes that activate it (CYTOCHROME P-450) and others that detoxify it (GLUTATHIONE S TRANSFERASE) (Pharmac Ther 50.443 1991). Primates & rat are sensitive while mouse and hamster are tolerant (Canc Res 29.236 1969).Aristolochic Acids: Nitro-phenanthrenes occurring in ARISTOLOCHIACEAE and other plants. They derive from stephanine (APORPHINES) by oxidative ring cleavage. The nitro group is a reactive alkylator (ALKYLATING AGENTS) that binds to biological macromolecules. Ingestion by humans is associated with nephropathy (NEPHRITIS). There is no relationship to the similar named aristolochene (SESQUITERPENES).Aflatoxins: Furano-furano-benzopyrans that are produced by ASPERGILLUS from STERIGMATOCYSTIN. They are structurally related to COUMARINS and easily oxidized to an epoxide form to become ALKYLATING AGENTS. Members of the group include AFLATOXIN B1; aflatoxin B2, aflatoxin G1, aflatoxin G2; AFLATOXIN M1; and aflatoxin M2.Aflatoxin B1: A potent hepatotoxic and hepatocarcinogenic mycotoxin produced by the Aspergillus flavus group of fungi. It is also mutagenic, teratogenic, and causes immunosuppression in animals. It is found as a contaminant in peanuts, cottonseed meal, corn, and other grains. The mycotoxin requires epoxidation to aflatoxin B1 2,3-oxide for activation. Microsomal monooxygenases biotransform the toxin to the less toxic metabolites aflatoxin M1 and Q1.Dactinomycin: A compound composed of a two CYCLIC PEPTIDES attached to a phenoxazine that is derived from STREPTOMYCES parvullus. It binds to DNA and inhibits RNA synthesis (transcription), with chain elongation more sensitive than initiation, termination, or release. As a result of impaired mRNA production, protein synthesis also declines after dactinomycin therapy. (From AMA Drug Evaluations Annual, 1993, p2015)Sulfinic Acids: Any of the monobasic inorganic or organic acids of sulfur with the general formula RSO(OH). (From McGraw Hill Dictionary of Scientific and Technical Terms, 4th ed)Flavonols: A group of 3-hydroxy-4-keto-FLAVONOIDS.Carbofuran: A cholinesterase inhibitor that is used as a systemic insecticide, an acaricide, and nematocide. (From Merck Index, 11th ed)GTP Cyclohydrolase: (GTP cyclohydrolase I) or GTP 7,8-8,9-dihydrolase (pyrophosphate-forming) (GTP cyclohydrolase II). An enzyme group that hydrolyzes the imidazole ring of GTP, releasing carbon-8 as formate. Two C-N bonds are hydrolyzed and the pentase unit is isomerized. This is the first step in the synthesis of folic acid from GTP. EC 3.5.4.16 (GTP cyclohydrolase I) and EC 3.5.4.25 (GTP cyclohydrolase II).Phosphorus-Oxygen Lyases: Enzymes that catalyze the cleavage of a phosphorus-oxygen bond by means other than hydrolysis or oxidation. EC 4.6.Shear Strength: The internal resistance of a material to moving some parts of it parallel to a fixed plane, in contrast to stretching (TENSILE STRENGTH) or compression (COMPRESSIVE STRENGTH). Ionic crystals are brittle because, when subjected to shear, ions of the same charge are brought next to each other, which causes repulsion.Stress, Mechanical: A purely physical condition which exists within any material because of strain or deformation by external forces or by non-uniform thermal expansion; expressed quantitatively in units of force per unit area.Endothelial Cells: Highly specialized EPITHELIAL CELLS that line the HEART; BLOOD VESSELS; and lymph vessels, forming the ENDOTHELIUM. They are polygonal in shape and joined together by TIGHT JUNCTIONS. The tight junctions allow for variable permeability to specific macromolecules that are transported across the endothelial layer.Patents as Topic: Exclusive legal rights or privileges applied to inventions, plants, etc.Inventions: A novel composition, device, or process, independently conceived de novo or derived from a pre-existing model.Intellectual Property: Property, such as patents, trademarks, and copyright, that results from creative effort. The Patent and Copyright Clause (Art. 1, Sec. 8, cl. 8) of the United States Constitution provides for promoting the progress of science and useful arts by securing for limited times to authors and inventors, the exclusive right to their respective writings and discoveries. (From Black's Law Dictionary, 5th ed, p1014)Foramen Ovale, Patent: A condition in which the FORAMEN OVALE in the ATRIAL SEPTUM fails to close shortly after birth. This results in abnormal communications between the two upper chambers of the heart. An isolated patent ovale foramen without other structural heart defects is usually of no hemodynamic significance.Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., GENETIC ENGINEERING) is a central focus; laboratory methods used include TRANSFECTION and CLONING technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction.History, 18th Century: Time period from 1701 through 1800 of the common era.Drug Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration.Blood Gas Monitoring, Transcutaneous: The noninvasive measurement or determination of the partial pressure (tension) of oxygen and/or carbon dioxide locally in the capillaries of a tissue by the application to the skin of a special set of electrodes. These electrodes contain photoelectric sensors capable of picking up the specific wavelengths of radiation emitted by oxygenated versus reduced hemoglobin.Transcutaneous Electric Nerve Stimulation: The use of specifically placed small electrodes to deliver electrical impulses across the SKIN to relieve PAIN. It is used less frequently to produce ANESTHESIA.Disclosure: Revealing of information, by oral or written communication.Persistent Fetal Circulation Syndrome: A syndrome of persistent PULMONARY HYPERTENSION in the newborn infant (INFANT, NEWBORN) without demonstrable HEART DISEASES. This neonatal condition can be caused by severe pulmonary vasoconstriction (reactive type), hypertrophy of pulmonary arterial muscle (hypertrophic type), or abnormally developed pulmonary arterioles (hypoplastic type). The newborn patient exhibits CYANOSIS and ACIDOSIS due to the persistence of fetal circulatory pattern of right-to-left shunting of blood through a patent ductus arteriosus (DUCTUS ARTERIOSUS, PATENT) and at times a patent foramen ovale (FORAMEN OVALE, PATENT).Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs.Sheep: Any of the ruminant mammals with curved horns in the genus Ovis, family Bovidae. They possess lachrymal grooves and interdigital glands, which are absent in GOATS.Neopterin: A pteridine derivative present in body fluids; elevated levels result from immune system activation, malignant disease, allograft rejection, and viral infections. (From Stedman, 26th ed) Neopterin also serves as a precursor in the biosynthesis of biopterin.Dextrans: A group of glucose polymers made by certain bacteria. Dextrans are used therapeutically as plasma volume expanders and anticoagulants. They are also commonly used in biological experimentation and in industry for a wide variety of purposes.Immune System: The body's defense mechanism against foreign organisms or substances and deviant native cells. It includes the humoral immune response and the cell-mediated response and consists of a complex of interrelated cellular, molecular, and genetic components.Iron-Dextran Complex: A complex of ferric oxyhydroxide with dextrans of 5000 to 7000 daltons in a viscous solution containing 50 mg/ml of iron. It is supplied as a parenteral preparation and is used as a hematinic. (Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, p1292)Handling (Psychology): Physical manipulation of animals and humans to induce a behavioral or other psychological reaction. In experimental psychology, the animal is handled to induce a stress situation or to study the effects of "gentling" or "mothering".

L-Ascorbic acid potentiates nitric oxide synthesis in endothelial cells. (1/830)

Ascorbic acid has been shown to enhance impaired endothelium-dependent vasodilation in patients with atherosclerosis by a mechanism that is thought to involve protection of nitric oxide (NO) from inactivation by free oxygen radicals. The present study in human endothelial cells from umbilical veins and coronary arteries investigates whether L-ascorbic acid additionally affects cellular NO synthesis. Endothelial cells were incubated for 24 h with 0.1-100 microM ascorbic acid and were subsequently stimulated for 15 min with ionomycin (2 microM) or thrombin (1 unit/ml) in the absence of extracellular ascorbate. Ascorbate pretreatment led to a 3-fold increase of the cellular production of NO measured as the formation of its co-product citrulline and as the accumulation of its effector molecule cGMP. The effect was saturated at 100 microM and followed a similar kinetics as seen for the uptake of ascorbate into the cells. The investigation of the precursor molecule L-gulonolactone and of different ascorbic acid derivatives suggests that the enediol structure of ascorbate is essential for its effect on NO synthesis. Ascorbic acid did not induce the expression of the NO synthase (NOS) protein nor enhance the uptake of the NOS substrate L-arginine into endothelial cells. The ascorbic acid effect was minimal when the citrulline formation was measured in cell lysates from ascorbate-pretreated cells in the presence of known cofactors for NOS activity. However, when the cofactor tetrahydrobiopterin was omitted from the assay, a similar potentiating effect of ascorbate pretreatment as seen in intact cells was demonstrated, suggesting that ascorbic acid may either enhance the availability of tetrahydrobiopterin or increase its affinity for the endothelial NOS. Our data suggest that intracellular ascorbic acid enhances NO synthesis in endothelial cells and that this may explain, in part, the beneficial vascular effects of ascorbic acid.  (+info)

Biopterin derivatives in normal and phenylketonuric patients after oral loads of L-phenylalanine, L-tyrosine, and L-tryptophan. (2/830)

Plasma biopterin derivatives studied in 10 normal and 21 phenylketonuric children showed a significantly high concentration in the latter group. Biopterin derivatives correlated with plasma phenylalanine concentration, but in normal adults given an oral phenylalanine load the rate of increase with phenylalanine differed from that in phenylketonuric patients. A patient with hyperphenylalaninaemia, not due to phenylketonuria, had an abnormal biopterin derivatives response to phenylalanine distinct from that of patients with classical phenylketonuria. This may be a useful investigation to differentiate some variants of phenylketonuria.  (+info)

Protective effects of 5,6,7,8-tetrahydroneopterin against X-ray radiation injury in mice. (3/830)

The protective effects of 5,6,7,8-tetrahydroneopterin (NH4) against radiation injury in mice were studied. (C57BL/6xA/J)F1 (B6A) mice received a single whole-body irradiation dose of 200, 400, 700 or 800 cGy of X-rays. NH4 (30 mg/kg body weight) or phosphate-buffered saline (PBS) was injected intraperitoneally into irradiated mice 10 min before and after the irradiation and again after 6 h. All mice which received the 800 cGy radiation+PBS died between 8 and 11 days after the treatment. In contrast, those which also received NH4 demonstrated a significantly prolonged survival time and 40% lived more than 5 months. Total numbers of thymocytes and spleen cells on day 5 post-irradiation were dramatically reduced in line with the radiation dose. The survival was significantly enhanced by NH4 in treated mice. The proliferation of spleen cells in mice stimulated by concanavalin A (Con A) or lipopolysaccharide (LPS) was also greater in NH4 treated mice. The immune response of survivors 5 months after 800 cGy+NH4 treatments, against Con A, LPS, allogenic mouse, and sheep red blood cells had essentially recovered to the levels of normal mice. These results indicate that NH4 had an important role in modifying radiation injury.  (+info)

Hypoxia inhibits increased ETB receptor-mediated NO synthesis in hypertensive rat lungs. (4/830)

Although hypertensive lungs of chronically hypoxic rats express increased levels of nitric oxide (NO) synthases (NOSs) and produce increased amounts of NO-containing compounds (NOx) during normoxic ventilation, the level of NO production during hypoxic exposure is unclear. Because hypoxia inhibits NO synthesis in normotensive lungs, we investigated whether hypoxic ventilation inhibited NO synthesis in isolated hypertensive lungs and chronically hypoxic rats. Measurement of perfusate NOx concentration in hypertensive lungs from male rats exposed to 4 wk of hypobaric hypoxia showed that basal NOx production was reduced during hypoxic (0% O2) vs. normoxic (21% O2) ventilation. Similarly, plasma NOx concentration was lower in chronically hypoxic rats breathing 10% O2 than in those breathing 21% O2. Hypoxic inhibition of lung NOx production was not prevented by supplementary L-arginine or tetrahydrobiopterin and was not mimicked by inhibition of Ca2+ influx. However, it was mimicked by inhibition of constitutive NOS with NG-monomethyl-L-arginine and chelation of intracellular Ca2+. The endothelin type B-receptor antagonist BQ-788 prevented the increases in NOx production associated with normoxic ventilation in both isolated hypertensive lungs and intact chronically hypoxic rats. These results suggest that a reduced supply of the cosubstrate molecular O2 to NOS counteracts an endothelin type B receptor-mediated stimulation of NO synthesis in hypertensive rat lungs. Thus, despite increased NOS protein in the lungs and pulmonary arteries of chronically hypoxic rats, direct hypoxic inhibition of NO production may contribute to the development of pulmonary hypertension.  (+info)

Enzymatic synthesis of biopterin from D-erythrodihydroneopterin triphosphate by extracts of kidneys from Syrian golden hamsters. (5/830)

An enzyme system was found in either crude homogenates of dialyzed extracts of liver, kidney, lung, and brain from Syrian golden hamsters that catalyzed the synthesis of radioactive 6(L-erythro-1',2'-dihydroxypropyl)pterin (biopterin) from [U-14C]6(D-erythro-1',2',3'-trihydroxypropyl)-7,8-dihydropterin triphosphate (D-erythrolH2neopterin-PPP) preparation. The specific radioactivity of biopterin was found to be comparable to that of D-erythroH2neopterin-PPP. The enzyme system from hamster kidney was purified severalfold by fractionation with ammonium sulfate and with an Ultrogel AcA-34 column. It was demonstrated that (a) NADPH or NADAH was essential and that (b) Mg2+ was stimulatory for the enzymatic synthesis of biopterin from D-erythroH2-NEOPTERIN-PPP. Also GTP and nonphosphorylated neopterins were not converted to biopterin. Although 6-lactyl-7,8-dihydropterin (sepiapterin) was converted to biopterin in the presence of NADPH, sepiapterin was not detected from D-erythroH2neopterin-PPP in the absence of NADPH. A preliminary experiment was performed to identify dihydrobiopterin.  (+info)

Sepiapterin reductase producing L-threo-dihydrobiopterin from Chlorobium tepidum. (6/830)

A novel type of NADPH-dependent sepiapterin reductase, which catalysed uniquely the reduction of sepiapterin to l-threo-dihydrobiopterin, was purified 533-fold from the cytosolic fraction of Chlorobium tepidum, with an overall yield of 3%. The native enzyme had a molecular mass of 55 kDa and SDS/PAGE revealed that the enzyme consists of two subunits with a molecular mass of 26 kDa. The enzyme was optimally active at pH8.8 and 50 degrees C. Apparent Km values for sepiapterin and NADPH were 21 and 6.2 microM, respectively, and the kcat value was 5.0 s-1. Diacetyl could also serve as a substrate, with a Km of 4.0 mM. The inhibitory effects of N-acetylserotonin, N-acetyldopamine and melatonin were very weak. The Ki value of N-acetyldopamine was measured as 400 microM. The N-terminal amino acid sequence was revealed as Met-Lys-His-Ile-Leu-Leu-Ile-Thr-Gly-Ala-Xaa-Lys - Lys - Ile - Xaa - Arg - Ala - Ile - Ala - Leu - Glu - Xaa - Ala - Arg - Xaa-Xaa-Xaa-His-His-His-, which shared relatively high sequence similarity with other sepiapterin reductases.  (+info)

Activation of neuronal nitric-oxide synthase by the 5-methyl analog of tetrahydrobiopterin. Functional evidence against reductive oxygen activation by the pterin cofactor. (7/830)

Tetrahydrobiopterin ((6R)-5,6,7,8-tetrahydro-L-biopterin (H4biopterin)) is an essential cofactor of nitric-oxide synthases (NOSs), but its role in enzyme function is not known. Binding of the pterin affects the electronic structure of the prosthetic heme group in the oxygenase domain and results in a pronounced stabilization of the active homodimeric structure of the protein. However, these allosteric effects are also produced by the potent pterin antagonist of NOS, 4-amino-H4biopterin, suggesting that the natural cofactor has an additional, as yet unknown catalytic function. Here we show that the 5-methyl analog of H4biopterin, which does not react with O2, is a functionally active pterin cofactor of neuronal NOS. Activation of the H4biopterin-free enzyme occurred in a biphasic manner with half-maximally effective concentrations of approximately 0.2 microM and 10 mM 5-methyl-H4biopterin. Thus, the affinity of the 5-methyl compound was 3 orders of magnitude lower than that of the natural cofactor, allowing the direct demonstration of the functional anticooperativity of the two pterin binding sites of dimeric NOS. In contrast to H4biopterin, which inactivates nitric oxide (NO) through nonenzymatic superoxide formation, up to 1 mM of the 5-methyl derivative did not consume O2 and had no effect on NO steady-state concentrations measured electrochemically with a Clark-type NO electrode. Therefore, reconstitution with 5-methyl-H4biopterin allowed, for the first time, the detection of enzymatic NO formation in the absence of superoxide or NO scavengers. These results unequivocally identify free NO as a NOS product and indicate that reductive O2 activation by the pterin cofactor is not essential to NO biosynthesis.  (+info)

Functionally important residues tyrosine-171 and serine-158 in sepiapterin reductase. (8/830)

The active site of sepiapterin reductase (SPR), which is a member of the NADP(H)-preferring short-chain dehydrogenase/reductase (SDR) family and acts as the terminal enzyme in the biosynthetic pathway of tetrahydrobiopterin cofactor (BH4), was investigated by truncation and site-directed mutagenesis. The truncation mutants showed that N-terminal and C-terminal residues contribute to bind coenzyme and substrate, respectively. The mutant rSPRA29V showed decreased activity; however, the A-X-L-L-S sequence, which has been reported as a putative pterin binding site, was estimated to preferably work as a component in the region for binding coenzyme rather than substrate. Site-directed mutants of rSPRS158D, rSPRY171V, and rSPRK175I showed low, but significant, activity having similar Km values and kcat/Km values less than 25%, for both sepiapterin and NADPH. Both amino acids Tyr-171 and Ser-158 are located within a similar distance to the carbonyl group of the substrate in the crystal structure of mouse SPR, and the double point mutant rSPRY171V+S158D was indicated to be inactive. These results showed that Ser-158, Tyr-171, and Lys-175 contributed to the catalytic activity of SPR, and both Tyr-171 and Ser-158 are simultaneously necessary on proton transfer to the carbonyl functional groups of substrate.  (+info)

*Biopterin

... compounds found within the body include both BH4 and BH2. Biopterin synthesis occurs through two principal pathways; ... Biopterin synthesis disorders are also a cause of hyperphenylalaninemia; phenylalanine metabolism requires BH4 as a cofactor. ... A number of disorders of biopterin regulation exist. Single-gene defects affecting the gene GCH1 block the first step in ... Mouse gene knockout models that block biopterin synthesis completely die shortly after birth due to their inability to produce ...

*Folate-biopterin transporter family

The folate-biopterin transporter (FBT) family (TC# 2.A.71) is a distant family within the major facilitator superfamily, most ... As of this edit, this article uses content from "2.A.71 The Folate-Biopterin Transporter (FBT) Family", which is licensed in a ... A related protein in Trypanosoma brucei, ESAGIO, shows weak folate/biopterin transport activity. There are at least 6 ... The probable transport reaction catalyzed by characterized FBT family members is: [folate, biopterin, or AdoMet] (out) + H+ ( ...

*Biopterin-dependent aromatic amino acid hydroxylase

... s (AAAH) are a family of aromatic amino acid hydroxylase enzymes which ...

*GTP cyclohydrolase I

GTPCH is part of the folate and biopterin biosynthesis pathways. It is responsible for the hydrolysis of guanosine triphosphate ... "Disorders of biopterin metabolism". Journal of Inherited Metabolic Disease. 32 (3): 333-42. doi:10.1007/s10545-009-1067-2. PMID ...

*6,7-dihydropteridine reductase

"Disorders of biopterin metabolism". Journal of Inherited Metabolic Disease. 32 (3): 333-42. doi:10.1007/s10545-009-1067-2. PMID ...

*Rett syndrome

"Cerebrospinal fluid biogenic amines and biopterin in Rett syndrome". Annals of Neurology. 25 (1): 56-60. doi:10.1002/ana. ...

*Tetrahydrobiopterin

... deficiency (THBD, BH4D) Biopterin Dihydrobiopterin Pteridine Całka, Jarosław (2006). "The role of nitric ...

*5-Hydroxytryptophan

Tryptophan hydroxylase is one of the biopterin-dependent aromatic amino acid hydroxylases. 5-HTP is decarboxylated to serotonin ...

*Hereditary folate malabsorption

... biopterin and neopterin concentrations". Molecular genetics and metabolism. 95 (3): 127-32. doi:10.1016/j.ymgme.2008.07.004. ...

*Tryptophan hydroxylase

Tyrosine hydroxylase, phenylalanine hydroxylase, and tryptophan hydroxylase together constitute the family of biopterin- ...

*Tyrosine hydroxylase

Sawada M, Hirata Y, Arai H, Iizuka R, Nagatsu T (Mar 1987). "Tyrosine hydroxylase, tryptophan hydroxylase, biopterin, and ...

*Dihydrofolate reductase

... relative importance of the de novo biopterin synthesis versus salvage pathways". The Journal of Biological Chemistry. 284 (41 ...

*PCBD1

"Hyperphenylalaninemia with high levels of 7-biopterin is associated with mutations in the PCBD gene encoding the bifunctional ...

*TPH1

Tryptophan hydroxylases catalyze the biopterin-dependent monooxygenation of tryptophan to 5-hydroxytryptophan (5-HTP), which is ...

*List of MeSH codes (D03)

... biopterin MeSH D03.438.733.631.202.500 --- neopterin MeSH D03.438.733.631.400 --- folic acid MeSH D03.438.733.631.400.600 --- ...

*FBT

Folate-biopterin transporter family Frost Bank Tower, in Austin, Texas, United States Greg Mueller (born 1971), Canadian poker ...

*Pteridine reductase

... biopterin + 2 NADPH + 2 H+ Thus, the two substrates of this enzyme are 5,6,7,8-tetrahydrobiopterin and NADP+, whereas its 3 ... products are biopterin, NADPH, and H+. This enzyme belongs to the family of oxidoreductases, specifically those acting on the ...

*Neopterin

https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene∂=ags NeoPterin.net Determination of neopterin and biopterin by liquid ...

*Transporter Classification Database

Family 2.A.71 The Folate-Biopterin Transporter (FBT) Family 2.A.72 The K+ Uptake Permease (KUP) Family 2.A.73 The Short Chain ...

*Phenylalanine hydroxylase

PAH is one of three members of the biopterin-dependent aromatic amino acid hydroxylases, a class of monooxygenase that uses ...

*Sepiapterin reductase deficiency

... but neopterin and biopterin were abnormal in only one sibling. The results of this research indicates that when diagnosing the ... quantification of sepiapterin in the CSF is more important and indicative of SR deficiency than using neopterin and biopterin ...

*List of disorders included in newborn screening programs

Tyrosinemia II Argininemia Benign hyperphenylalaninemia Defects of biopterin cofactor biosynthesis Defects of biopterin ...
Tetrahydrobiopterin deficiency (THBD, BH4D), also called THB or BH4 deficiency, is a rare metabolic disorder that increases the blood levels of phenylalanine. Phenylalanine is an amino acid obtained through the diet. It is found in all proteins and in some artificial sweeteners. If tetrahydrobiopterin deficiency is not treated, excess phenylalanine can build up to harmful levels in the body, causing intellectual disability and other serious health problems. High levels of phenylalanine are present from infancy in people with untreated tetrahydrobiopterin (THB, BH4) deficiency. The resulting signs and symptoms range from mild to severe. Mild complications may include temporary low muscle tone. Severe complications include intellectual disability, movement disorders, difficulty swallowing, seizures, behavioral problems, progressive problems with development, and an inability to control body temperature. It was first characterized in 1975. This condition is inherited in an autosomal recessive ...
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 ...
Overproduction of nitric oxide (NO) is thought to be a key mediator of the vascular dysfunction and severe hypotension in patients with endotoxaemia and septic shock. The contribution of NO produced directly in the vasculature by endothelial cells to the hypotension seen in these conditions, vs. the broader systemic increase in NO, is unclear. To determine the specific role of endothelium derived NO in lipopolysaccharide (LPS)-induced vascular dysfunction we administered LPS to mice deficient in endothelial cell tetrahydrobiopterin (BH4), the essential co-factor for NO production by NOS enzymes. Mice deficient in endothelial BH4 production, through loss of the essential biosynthesis enzyme Gch1 (Gch1(fl/fl)Tie2cre mice) received a 24hour challenge with LPS or saline control. In vivo LPS treatment increased vascular GTP cyclohydrolase and BH4 levels in aortas, lungs and hearts, but this increase was significantly attenuated in Gch1(fl/fl)Tie2cre mice, which were also partially protected from the LPS
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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 ...
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 ...
In this study, we describe a new double-transgenic mouse model in which endothelial-targeted overexpression of GTPCH leads to increased endothelial BH4 levels in mice with endothelial-targeted eNOS overexpression. We used this model to investigate the role of BH4 in the regulation of eNOS coupling in vivo, specifically in the absence of pathological oxidative stress associated with vascular disease states.6 The major findings in this study are as follows. First, eNOS protein levels are markedly elevated in eNOS-Tg and eNOS/GCH-Tg mice but not in GCH-Tg animals, although the proportion of eNOS dimer to monomer is depleted only in eNOS-Tg aortas. Second, endothelial-specific overexpression of GTPCH is sufficient to increase vascular BH4 levels in GCH-Tg and in eNOS/GCH-Tg aortas, whereas BH4 levels are depleted in eNOS-Tg aortas. Third, this increase in BH4 is sufficient to augment vascular eNOS enzymatic activity even in GCH-Tg mice, which have unchanged eNOS protein levels. Indeed, eNOS activity ...
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 ...
BACKGROUND Nitric oxide synthase uncoupling occurs under conditions of oxidative stress modifying the enzymes function so it generates superoxide rather than nitric oxide. Nitric oxide synthase uncoupling occurs with chronic pressure overload, and both are ameliorated by exogenous tetrahydrobiopterin (BH4)-a cofactor required for normal nitric oxide synthase function-supporting a pathophysiological link. Genetically augmenting BH4 synthesis in endothelial cells fails to replicate this benefit, indicating that other cell types dominate the effects of exogenous BH4 administration. We tested whether the primary cellular target of BH4 is the cardiomyocyte or whether other novel mechanisms are invoked. METHODS AND RESULTS Mice with cardiomyocyte-specific overexpression of GTP cyclohydrolase 1 (mGCH1) and wild-type littermates underwent transverse aortic constriction. The mGCH1 mice had markedly increased myocardial BH4 and, unlike wild type, maintained nitric oxide synthase coupling after transverse
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 ...
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 ...
The International Conference on Tetrahydrobiopterin, PKU, and NOS Will take place March 23-28, 2008 in St. Moritz - Champfér, Switzerland For more information, visit http://www.pku-bh4.com/index.asp Thank you very much in advance for your contributions to this blog (Click on login to register and post a comment). Click this link to see the most recent online […]. ...
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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.
You have two copies of a GCH1 variant associated with lower levels of tetrahydrobiopterin (BH4) and total biopterins. BH4 is used in the production of several neurotransmitters, including serotonin and dopamine. While many people carry this with no obvious ill effects, it does seem noteworthy. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2699614/ reports median plasma BH4 levels in patients with this genotype were reduced by approximately 80%. Several potentially serious health issues could result from an 80% reduction in BH4 levels. There may not be enough BH4 to convert phenylalanine to tyrosine. Therefore, phenylalanine can build up in body tissue and cause health issues (like high blood pressure). But, now there may not be enough tyrosine, which is needed to create dopamine. And so then there may not be enough dopamine, which can possibly lead to symptoms SIMILAR to conditions like Fibromyalgia and Parkinsons (but not actually Parkinsons). People who have low levels of tyrosine, and ...
Im not sure where to post this type of question, couldnt find an exact match, so forgive me if its in the wrong place. I havent been on BH for a while. But I find myself unexpectedly pregnant with our fourth (!!!!) baby and we are not - page 4
Is there anyone else out there on BH land that is also waiting to TTC later this year/early next year? Curious to hear why others are waiting and perhaps we can all help make the time go faster together!!! - page 66
Guppy is a popular ornamental fish owing to its diverse body and fin coloration. More than 40 established color varieties have been selectively bred. The complementary DNAs for 2 enzymes that are involved in the de novo synthesis of pteridines and purines, which are important for the production of color pigments, were cloned from the caudal fin. Two cDNA isoforms for 6-pyruvoyl tetrahydropterin synthase (PTPS), with an open reading frame of 130 and 147 amino acids, respectively, were cloned from the Red Tail variety. The deduced amino acid sequence of the longer isoform shows an overall identity of about 65% to the mammalian PTPS sequences. The cDNA for xanthine dehydrogenase (XDH) was cloned from the Yellow Tail variety, and consists of an open reading frame of 1331 amino acids. Although it shows a higher overall identity to bovine aldehyde oxidase (AO; 54%) than to chicken XDH (51%), it has a NAD-binding domain that is specific to XDHs. Northern blot analysis indicated that both PTPS and XDH ...
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 ...
Excessive intimal hyperplasia, the principal cause of PCI failure, is associated with reduced endothelial nitric oxide (NO) bioavailability. Tetrahydrobiopterin (BH4) is a required cofactor for NO synthesis by endothelial nitric oxide synthase (eNOS). We investigated the importance of BH4 in regulating intimal hyperplasia using a transgenic mouse with endothelial overexpression of the rate-limiting enzyme in BH4 synthesis, GTP-cyclohydrolase I (GCH). Angioplasty and stenting was performed on aortic segments from donor transgenic mice crossed onto ApoE-KO background (GCH-Tg/ApoE-KO) or their ApoE-KO littermates (n=16), using a novel model of stenting in mice where the stented donor aortic segment is grafted into the carotid artery of isogenic recipients. Aortic BH4 levels were 8-fold higher in GCH-Tg/ApoE-KO mice compared with ApoE-KO controls. (P,0.01). Despite equal stent expansion and injury scores, intimal hyperplasia was reduced by 47% (P,0.001) in GCH-Tg/ApoE-KO mice. Aortic NO synthesis, ...
AIMS: Clinical markers of cardiac autonomic function, such as heart rate and response to exercise, are important predictors of cardiovascular risk. Tetrahydrobiopterin (BH4) is a required cofactor for enzymes with roles in cardiac autonomic function, including tyrosine hydroxylase and nitric oxide synthase. Synthesis of BH4 is regulated by GTP cyclohydrolase I (GTPCH), encoded by GCH1. Recent clinical studies report associations between GCH1 variants and increased heart rate, but the mechanistic importance of GCH1 and BH4 in autonomic function remains unclear. We investigate the effect of BH4 deficiency on the autonomic regulation of heart rate in the hph-1 mouse model of BH4 deficiency. METHODS AND RESULTS: In the hph-1 mouse, reduced cardiac GCH1 expression, GTPCH enzymatic activity, and BH4 were associated with increased resting heart rate; blood pressure was not different. Exercise training decreased resting heart rate, but hph-1 mice retained a relative tachycardia. Vagal nerve stimulation in vitro
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.
OBJECTIVE: When the availability of tetrahydrobiopterin (BH4) is deficient, endothelial nitric oxide synthase (eNOS) produces superoxide rather than NO (uncoupled eNOS). We have shown that the atherosclerotic lesion size was augmented in apolipoprotein E-deficient (ApoE-KO) mice overexpressing eNOS because of the enhanced superoxide production. In this study, we addressed the specific importance of uncoupled eNOS in atherosclerosis, and the potential mechanistic role for specific versus nonspecific antioxidant strategies in restoring eNOS coupling. METHODS AND RESULTS: We crossed mice overexpressing eNOS in the endothelium (eNOS-Tg) with mice overexpressing GTP-cyclohydrolase I (GCH), the rate-limiting enzyme in BH4 synthesis, to generate ApoE-KO/eNOS-Tg/GCH-Tg mice. As a comparison, ApoE-KO/eNOS-Tg mice were treated with vitamin C. Atherosclerotic lesion formation was increased in ApoE-KO/eNOS-Tg mice compared with ApoE-KO mice. GCH overexpression in ApoE-KO/eNOS-Tg/GCH-Tg mice increased vascular BH4
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 ...
The nitric oxide synthases are dimeric enzymes in which the intersubunit contacts are formed by the P-450-haem-containing, tetrahydrobiopterin-dependent oxygenase domain. The dimerization of the neuronal isoenzyme was shown previously to be triggered by Fe-protoporphyrin IX (haemin). We report for the first time the reactivation of the haem-deficient neuronal isoenzyme (from rat, expressed in a baculovirus/insect cell system) after haem reconstitution. We further examined the reconstitution of the enzyme with protoporphyrin IX (PPIX) and its Mn and Co complexes. All of these porphyrins inserted into the haem pocket, as assessed by quenching of intrinsic protein fluorescence. In addition to haemin, MnPPIX stimulated dimerization, as measured by gel filtration and by cross-linking with glutaraldehyde. In contrast, neither CoPPIX nor PPIX stimulated dimerization. The absorbance spectra of the reconstituted enzymes were measured and compared with published results on P-450 enzymes reconstituted with ...
Dihydrofolate reductase (DHFR) is a critical enzyme in folate metabolism and an important target of antineoplastic, antimicrobial, and antiinflammatory drugs. We describe three individuals from two families with a recessive inborn error of metabolism, characterized by megaloblastic anemia and/or pancytopenia, severe cerebral folate deficiency, and cerebral tetrahydrobiopterin deficiency due to a germline missense mutation in DHFR, resulting in profound enzyme deficiency. We show that cerebral folate levels, anemia, and pancytopenia of DHFR deficiency can be corrected by treatment with folinic acid. The characterization of this disorder provides evidence for the link between DHFR and metabolism of cerebral tetrahydrobiopterin, which is required for the formation of dopamine, serotonin, and norepinephrine and for the hydroxylation of aromatic amino acids. Moreover, this relationship provides insight into the role of folates in neurological conditions, including depression, Alzheimer disease, and ...
A recent study suggests that potentially treatable metabolic abnormalities in the central nervous system may underlie a large proportion of cases of severe, treatment-resistant depression. These abnormalities, such as folate deficiency in the cerebrospinal fluid, are not screened for regularly, as they require a spinal tap to diagnose.. Researchers led by Lisa A. Pan were inspired to assess metabolic function in people with treatment-resistant depression after a young patient with severe, persistent depression who had attempted suicide several times improved dramatically after being diagnosed with a tetrahydrobiopterin deficiency in his cerebrospinal fluid and treated for the deficiency. Tetrahydrobiopterin is critical to the production of monoamine neurotransmitters.. The researchers carried out a case-control study of 33 teen and young adult patients who had had treatment-resistant depression since childhood and 16 healthy control participants. Twenty-one of the 33 patients with severe ...
TY - JOUR. T1 - Tetrahydrobiopterin (BH4) and superoxide dismutase (SOD) synergistically augment endothelium-dependent relaxations in canine middle cerebral artery. AU - Tsutsui, M.. AU - Milstien, S.. AU - Katusic, Zvonimir S. PY - 1996. Y1 - 1996. N2 - BH4 is an essential cofactor required for activation of nitric oxide synthase. The present study was designed to determine the effect of an increase in endogenous BH4 on endothelium-dependent relaxations in canine middle cerebral arteries. Segments of the isolated arteries were incubated (24 h at 37°C) in minimum essential medium in the presence and in the absence of a tetrahydrobiopterin precursor, sepiapterin (10-4M), and/or SOD (150 U/ml). The arteries were suspended for isometric tension recording. BH4 levels were assayed by high performance liquid chromatography. Levels of cGMP were measured by radioimmunoassay. All experiments were performed in the presence of indomethacin (10-5 M). Incubation with sepiapterin markedly increased ...
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 - 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 ...
Sigma-Aldrich offers abstracts and full-text articles by [Anna Starr, Claire A Sand, Lamia Heikal, Peter D Kelly, Domenico Spina, Mark Crabtree, Keith M Channon, James M Leiper, Manasi Nandi].
Germanys Merck KGaA has submitted an application with European regulators to get marketing approval for sapropterin as an oral treatment for hyperphenylalaninemia (HPA). - News - PharmaTimes
Several recent studies have provided compelling evidence for increased ROS generation in the vascular tissues of SHR.13 22 23 24 For instance, using fluorescence microscopy, Suzuki et al23 have demonstrated enhanced superoxide production in mesenteric arterioles of SHR in vivo. Likewise Grunfeld et al24 have reported increased superoxide generation in cultured aortic endothelial cells from SHR compared with corresponding cells from WKY. Moreover, Cosentino et al13 have shown increased superoxide and hydrogen peroxide release in aortic strips prepared from SHR. ROS are thought to contribute to the generation and/or maintenance of hypertension in SHR by several mechanisms. These include inactivation of endothelium-derived NO,12 14 nonenzymatic generation of vasoconstrictive F2-isoprostanes from arachidonic acid peroxidation,15 and depletion of the NOS cofactor tetrahydrobiopterin.13 The role of oxidative stress in the genesis and maintenance of hypertension in SHR is supported by amelioration of ...
Tetrahydrobiopterin (BH4) is a naturally occurring cofactor essential for critical metabolic pathways. Studies suggest that BH4 supplementation may ameliorate autism symptoms; the biological mechanism for such an effect is unknown. To help understand the relation between central BH4 concentration and systemic metabolism and to develop a biomarker of central BH4 concentration, the relationship between cerebrospinal fluid BH4 concentration and serum amino acids was studied. BH4 concentration was found to be distributed in two groups, a lower and higher BH4 concentration group. Two serum amino acids, citrulline and methionine, differentiated these groups, and the ratio of serum citrulline-to-methionine was found to correlate with the cerebrospinal fluid BH4 concentration (r = -0.67, p
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 ...
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GCH1 encodes GTPCH1, the rate-limiting enzyme for BH4 synthesis. Im curious to find out if anyone else has a mutation to this gene because low BH4...
Im 31 weeks and this weekend have started to notice a pattern in BH. I get them from 8-10 every morning and theyre actually pretty painful. I thought I was going to have to call the doc yesterday as they were timeable and not letting up. This is my3rd and I dont remember this with the other 2. Any other ladies experience this?
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 ...
According to recent investigations neopterin (a pyrazinopyrimidine derivative) is a biochemical marker that reflects the activity of the proinflammatory immunocellular system of the synovial tissue in rheumatoid arthritis (RA). Interferon gamma, derived from antigen activated T lymphocytes, stimulates macrophages to synthesise and release neopterin into the culture supernatant in vitro. To extend this in vitro model to a clinical level a sensitive new radioimmunoassay technique was used to measure neopterin concentrations in the synovial fluid (SF) of 17 patients with active RA, nine with osteoarthritis, and six with acute gout, and in that of 12 controls undergoing meniscectomy. The SF neopterin concentrations were significantly higher in patients with RA than in the other groups of patients, particularly the controls. Multivariant analysis showed that SF neopterin concentrations correspond better with the systemic inflammatory activity of RA than with the local disease activity of the knee ...
5-Bromo-2-hydroxypyrimidine 38353-06-9 MSDS report, 5-Bromo-2-hydroxypyrimidine MSDS safety technical specifications search, 5-Bromo-2-hydroxypyrimidine safety information specifications ect.
Tetrahydrobiopterin (BH4) is an essential cofactor for dopamine (DA), noradrenaline (NA), serotonin and nitric oxide (NO) synthesis in the brain. Inborn errors of BH4 metabolism including GTP cyclohydrolase 1 (GTP-CH) deficiency are debilitating diseases in which BH4, DA, 5-HT and NO metabolism are impaired. Current treatment for these disorders is typically monoamine replacement +/- BH4. Whilst correction of the primary defect is the ideal, BH4 treatment is problematic as it is expensive and inefficacious. One approach to treat BH4 disorders is to use gene therapy as a more permanent, effective alternative. In this thesis the potential of gene therapy in an animal model of partial BH4 deficiency, the hph-1 mouse, was examined. These mice show many neurochemical similarities associated with BH4 deficient states, including impaired BH4 (-69%), DA (-14%), NA (-23%), serotonin turnover (-55%) and NO metabolites in the brain. In cultured astrocytes from hph-1 mice BH4 was significantly lower than ...
The IUPHAR/BPS Guide to Pharmacology. L-Phenylalanine hydroxylase - Amino acid hydroxylases. Detailed annotation on the structure, function, physiology, pharmacology and clinical relevance of drug targets.
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
Results Four patients died soon after the initial treatment because of the deterioration of RPILD. At onset of the disease, the levels of serum anti-MDA5 antibody and neopterin were extremely high (169.75±24.3 index and 27.6±24.1 nmol/l) in all patients. However serum IL-18 level was almost normal (479.3±301.4 pg/ml). Among the 9 surviving patients, it took about one year for anti-MDA5 antibody level to decrease to the normal range. On the other hand, neopterin level decreased quickly after the initial treatment. The level of anti-MDA5 antibody transitioned from 169.75±24.3 index to 93.1±50.1 index, and then to 44.8±45.4 index (P=0.003). Neopterin level transitioned from 27.6±24.1 nmol/l to 9.1±6.5 nmol/l, and then to 6.4±5.0 nmol/l (P=0.006). IL-18 level transitioned from 479.3±301.4 pg/ml to 246.0±175.8 pg/ml, and then to 233.3±180.1 pg/ml (P=0.02). The level of anti-MDA5 didnt correlate with the level of ferritin (r=0.28), neopterin (r=0.16), IL-18 (r=0.06) and soluble IL-2 ...
This study is an independent sub-study of the protocol titled PKU-016: A double-blind, placebo-controlled, randomized study to evaluate the safety and therapeutic effects of sapropterin dihydrochloride on neuro-psychiatric symptoms in subjects with phenylketonuria (PKU ASCEND).. The primary objective of this study is to determine oxidative stress in patients with classical phenylketonuria (PKU) enrolled in PKU-016, using a brain scan (called an HMPAO SPECT) at baseline and 26 weeks, and blood redox biomarkers. ...
This study is an independent sub-study of the protocol titled PKU-016: A double-blind, placebo-controlled, randomized study to evaluate the safety and therapeutic effects of sapropterin dihydrochloride on neuro-psychiatric symptoms in subjects with phenylketonuria (PKU ASCEND).. The primary objective of this study is to determine oxidative stress in patients with classical phenylketonuria (PKU) enrolled in PKU-016, using a brain scan (called an HMPAO SPECT) at baseline and 26 weeks, and blood redox biomarkers. ...
In this study, we have for the first time demonstrated that ONOO− releases zinc from GTPCH1 and that zinc removal lowers GTPCH1 activity. Further, zinc-deleted GTPCH1 exhibits increased ubiquitination and reduced stability. We found that ONOO− generated by high glucose suppresses GTPCH1 activity along with increased ubiquitination and destruction of this enzyme. Finally, GTPCH1 ubiquitination and destruction is markedly increased in parallel with enhanced ONOO− in STZ-induced diabetic mice in vivo. Overall, our results suggest that ONOO− releases zinc, inhibits GTPCH1 activity, and increases GTPCH1 ubiquitination.. The major finding of this study is that ONOO− removes the zinc in GTPCH1, resulting in enzyme inhibition. Several lines of evidence are consistent with the hypothesis that loss of zinc by ONOO− oxidation underlies the inactivation of GTPCH1. First, ONOO− dose-dependently releases zinc from GTPCH1 (Fig. 1B). Second, the effects of ONOO− are mimicked by TPEN, a selective ...
Nitric oxide synthases (NOS) are haem-containing oxidoreductases and exist as homodimers in three isoforms: endothelial (eNOS), neuronal (nNOS), and inducible (iNOS). They produce NO through a 5-step oxidation of its substrate L-arginine to L-citrulline, using molecular oxygen. The C-terminal reductase domain of NOS contains binding sites for FAD, FMN and the electron donor, NADPH (Fig 3). The N-terminal oxygenase domain contains the haem group and binding sites for the substrate, arginine and the cofactor, BH4. The reductase domain generates electron flow from NADPH through the flavins FAD and FMN and then transfers the electrons to the oxygenase domain of the other monomer, where L-arginine oxidation occurs at the haem group in the active site [4].. In the vasculature, eNOS is the main NOS isoform, constitutively expressed in normal endothelium, while iNOS expression is normally low but may be increased in certain disease states, such as atherosclerosis [88]. eNOS is localized to invaginations ...
Sengupta S and Chandra T.S , Molecular and structural characterization of GTP-cyclohydrolase II in Eremothecium ashbyi NRRL Y-1363: cDNA cloning, comparative sequence analysis and molecular modeling . Fungal Biology 2010 doi:10.1016/j.funbio.2010.06.006 Copyright © 2010 The British Mycological Society Published by Elsevier Ltd (originally called Mycological Research ...
Campbell MG et al., 2013. Pathway-based outlier method reveals heterogeneous genomic structure of autism in blood transcriptome. BMC Med Genomics 6:34. doi: 10.1186/1755-8794-6-34. Frye, R et al., 2012. Metabolic effects of tetrahydrobiopterin treatment. INSAR Meeting, May 18,, Sheraton Hall, Toronto. https://imfar.confex.com/imfar/2012/webprogram/Paper11063.html Frye RE et al., 2013. Metabolic effects of sapropterin treatment in autism spectrum disorder:…
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Top ⭐ 16 reasons for Audio-Technica ATH-WS33X vs Yamaha HPH-200: 1. Highest frequency: 23000 vs 20000 2. Lowest frequency: 10 vs 20 3. Weight: 150 vs 180
Nicotinamide adenine dinucleotide (NAD) is an essential cofactor found in all living cells, essential for energy production. To get a... ...
The study was conducted among 92 male workers, divided into two groups depending on workplace and level of inorganic dust containing free crystalline SiO2 in the work environment, and 43 healthy workers without exposure to dust aerosols. The measured inhalable and respirable dust concentrations, as well as the concentration of free crystalline silica (FCS) in the respirable fraction were different for the two groups, but the percentage of free crystalline silica in the respirable fraction was almost identical. Significantly higher neopterin levels were found in workers exposed to dust, compared to the control group: 12.72 nmol/L and 6.32 nmol/L respectively (p,0.05). No significant difference was found between serum neopterin levels in both groups of the exposed workers. Among the groups with different length of service, a statistically higher neopterin level was evident only in the workers with length of service less than 10 years (p,0.05). The correlation analysis did not find a significant ...
It has been reported that corticotropin-releasing factor (CRF) is involved in the regulation of norepinephrine neuron responses to stress such as an immobilized stress. Furthermore, systemic lipopolysaccharide (LPS) injection upregulates the transcription of the genes encoding CRF and CRF type 1 receptor in the paraventricular nucleus of the hypothalamus. We have already reported that an increase in norepinephrine turnover within the murine locus coeruleus is accompanied by septic shock triggered by LPS intraperitoneal injection. We also elucidated that the expression levels of the enzymes involved in the catecholamine biosynthesis were altered by peripheral LPS injection. Collectively, the effects of CRF on the expression levels of the enzymes at murine locus coeruleus were investigated by peripherally injecting CP-154,526, a CRF receptor type 1 antagonist. Pretreatment with CP-154,526 attenuated the increase in expression levels of GTP cyclohydrolase I mRNA due to intraperitoneal LPS injection at 4 h
The aim of this study was to establish levels of the enzymes involved in tetrahydrobiopterin (BH4) metabolism in human and rat brain preparations; to determine whether BH4 metabolism is altered in dementia, particularly in relation to senile dementia of the Alzheimer type (SDAT); and to examine the effect of aluminium on BH4 metabolism. Overall BH4 synthesis and dihydropteridine reductase (DHPR) activity were greater in the locus coeruleus than in the neocortex of elderly subjects. Sepiapterin reductase and DHPR activity showed a linear correlation with age in the temporal cortex. DHPR activity in the frontal cortex was relatively constant until the mid 60s and then fell with age. Overall BH4 synthesis showed a non-significant decline in temporal cortex and was significantly reduced in locus coeruleus preparations from SDAT subjects compared to control subjects. As DHPR, sepiapterin reductase and GTP cyclohydrolase activity were unaltered in SDAT we suggested that there is a lesion on the ...
Queuosine is a modified pyrrolopyrimidine nucleoside found in the anticodon loop of transfer RNA acceptors for the amino acids tyrosine, asparagine, aspartic acid, and histidine. Since it is exclusively synthesised by bacteria, higher eukaryotes must salvage queuosine or its nucleobase queuine from food and the gut microflora. Previously, animals made deficient in queuine died within 18 days of withdrawing tyrosine-a non-essential amino acid-from the diet [Marks T, Farkas WR (1997) Biochem Biophys Res Commun 230:233-7]. Here we show that human HepG2 cells deficient in queuine and mice made deficient in queuosine modified transfer RNA, by disruption of the tRNA guanine transglycosylae (TGT) enzyme, are compromised in their ability to produce tyrosine from phenylalanine. This has similarities to the disease phenylketonuria, which arises from mutation in the enzyme phenylalanine hydroxylase or from a decrease in the supply of its cofactor tetrahydrobiopterin (BH4). Immunoblot and kinetic analysis ...
Metabolic variations occur during normal pregnancy to provide the growing fetus with a supply of nutrients required for its development and to ensure the health of the woman during gestation. Mass spectrometry-based metabolomics was employed to study the metabolic phenotype variations in the maternal plasma that are induced by pregnancy in each of its three trimesters. Nontargeted metabolomics analysis showed that pregnancy significantly altered the profile of metabolites in maternal plasma. The levels of six metabolites were found to change significantly throughout pregnancy, with related metabolic pathway variations observed in biopterin metabolism, phospholipid metabolism, amino acid derivatives, and fatty acid oxidation. In particular, there was a pronounced elevation of dihydrobiopterin (BH2), a compound produced in the synthesis of dopa, dopamine, norepinephrine, and epinephrine, in the second trimester, whereas it was markedly decreased in the third trimester. The turnover of BH2 and tryptophan
Materials. Guanabenz was purchased from Research Biochemicals International (Natick, MA). Glucose 6-phosphate, glucose 6-phosphate dehydrogenase, NADP+, NG-nitro-l-arginine, l-arginine, d-arginine, dihydropteridine reductase from sheep liver, calmodulin, catalase, superoxide dismutase, and NADPH were purchased from Sigma Aldrich (St. Louis, MO). Male Wistar rats were purchased from Charles River Laboratories (Wilmington, MA). (6R)-5,6,7,8-Tetrahydro-l-biopterin (BH4) was purchased from Dr. Schirks Laboratory (Jona, Switzerland). The affinity-purified rabbit IgG against brain NOS used for immunoblotting nNOS was from BD Biosciences Transduction Laboratories (Lexington, KY). [Benzylidene carbon 14C]-labeled guanabenz (56 mCi/mmol) was custom-synthesized by Du Pont NEN (Boston, MA). l-[14C(U)]-Arginine (330.0 mCi/mmol) and 125I-labeled antibody against rabbit IgG were purchased from PerkinElmer Life and Analytical Sciences (Boston, MA).. Methods.In vitro inhibition assays. For studies on the ...
GTP cyclohydrolase I (encoded by gene folE) is the first Zn(2+)-dependent enzyme of the de novo tetrahydrofolate biosynthetic pathway. It presents in bacteria, fungi, and plants. It catalyzes the conversion of GTP to 7,8-dihydroneopterin triphosphate. The 2.1A resolution structure of GTP cyclohydrolase I from Yersinia pestis CO92 is a pentomer in the asymmetric unit. The structure contains, in the active site, five GTP molecules and Ca(2+) ions probably from crystallization in place of Zn(2+) determined by atomic distances and fluorescence spectrum ...
S)-2-Hydroxypropylphosphonic Acid Epoxidase (HppE). (S)-2-Hydroxylpropanylphosphonic acid epoxidase (HppE), which catalyzes the last step of the biosynthesis of fosfomycin (21), a clinically useful antibiotic, has been identified as a new member of the mononuclear non-heme iron-dependent enzyme family. Earlier studies have shown that molecular oxygen is essential for the reaction. However, neither of the oxygen atoms is incorporated into the fosfomycin product; instead, both are reduced to water. The true source of the oxygen atom of the epoxy ring in 21 has been established to be the secondary hydroxyl group of HPP (22) (Scheme 7). Thus, the conversion of 22 to 21 by HppE is a novel epoxidation reaction since it is effectively a dehydrogenation reaction. In contrast to most mononuclear non-heme iron-dependent enzymes that reduce oxygen completely to water, HppE does not depend on tetrahydrobiopterin, α-keto acids, or ascorbate as co-substrate to provide the necessary reducing equivalents ...
GIUGLIANI, Luciana et al. Tetrahydrobiopterin responsiveness of patients with phenylalanine hydroxylase deficiency. J. Pediatr. (Rio J.) [online]. 2011, vol.87, n.3, pp.245-251. ISSN 0021-7557. http://dx.doi.org/10.2223/JPED.2090.. OBJECTIVE: To identify patients responsive to tetrahydrobiopterin (BH4) in a sample of Brazilians with hyperphenylalaninemia due to phenylalanine hydroxylase deficiency (HPA-PAH). METHODS: Interventional study, convenience sampling. The inclusion criteria were: diagnosis of HPA-PAH; age , 7 years; phenylalanine-restricted diet and phenylalanine (Phe) levels , 6 mg/dL in all blood tests 1 year before inclusion. Blood samples were obtained the day before (day 1) and at 0, 4, 8 (day 2) and 24 h (day 3) after BH4 intake. Phe levels were measured using tandem mass spectrometry. The criteria used to define responsiveness to BH4 were: criterion 1- Phe reduction , 30% 8 h after BH4 administration; criterion 2 - Phe reduction , 30% 24 h after BH4 administration. RESULTS: ...
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.. ...
BackgroundInflammatory markers show significant associations with cardiovascular events and all-cause mortality after kidney transplantation. Neopterin, reflecting interferon--release, may better reflect the proinflammatory state of recipients than less specific markers. MethodsKidney transplant recipients in the Assessment of LEscol in Renal Transplant (ALERT) trial were examined and investigated for an association between serum neopterin and subsequent clinical events: graft loss, major cardiovascular events (MACE) and all-cause mortality. ResultsAfter adjustment for established and emerging risk factors neopterin expressed as neopterin-to-creatinine ratio was significantly associated with MACE (p=0.009) and all-cause mortality (p=0.002). Endpoints were more frequent with increasing quartiles of neopterin-to-creatinine ratio. The incidence rates of MACE and all-cause mortality were significantly increased in the upper quartiles compared with the first. ConclusionsThis long-term prospective ...
Neurometabolic disorders: Potentially treatable abnormalities in patients with treatment-refractory depression and suicidal behaviorPan LA, Martin P, Zimmer T, Segreti AM, Kassiff S, McKain BW, Baca CA, Rengasamy M, Hyland K, Walano N, Steinfeld R, Hughes M, Dobrowolski SK, Pasquino M, Diler D, Perel J, Finegold DN, Peters DG, Naviaux RK, Brent DA and Vockley J.American Journal of Psychiatry, 2017, 174(1):42-50Treatment-refractory depression is a devastating condition with significant morbidity, mortality, and societal cost. At least 15% of cases of major depressive disorder remain refractory to treatment. Dr. Lisa Pan and her colleagues previously identified a young adult with treatment-refractory depression and multiple suicide attempts with an associated severe deficiency of CSF tetrahydrobiopterin, a critical cofactor for monoamine neurotransmitter synthesis. Treatment with sapropterin, a tetrahydrobiopterin analogue, led to dramatic and long-lasting remission of depression. This sentinel case led
Low-grade immune activation is common in people living with HIV (PLHIV), despite long-term viral suppression by antiretroviral therapy (ART). The clinical significance of this activation remains unclear. The aim of this study was to examine residual intrathecal immune activation in relation to signs of neuronal injury and neurocognitive impairment in PLHIV who had been virally suppressed on ART > 10 years.Twenty neuroasymptomatic PLHIV on suppressive ART for a median of 13.2 years were retrospectively identified from the longitudinal prospective Gothenburg HIV cerebrospinal fluid (CSF) study. HIV-RNA, neopterin, and neurofilament light protein (NFL) levels were measured in paired plasma and CSF samples. Pre-treatment samples were available for 14 subjects. Cognitive function was assessed by CogState at follow-up.CSF neopterin decreased from a median (IQR) of 17.8 (10.6-29.7) to 6.1 (4.6-8.0) nmol/L during treatment (p < 0.001). In 11 out of 20 participants (55%), CSF neopterin levels were above ...
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Complete information for PTS gene (Protein Coding), 6-Pyruvoyltetrahydropterin Synthase, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
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...
Univ.-Prof. Dr. med., Prof. h.c. (RCH) Georg F. Hoffmann. A. If the GTPCH deficiency of a child appearing in this question is autosomal dominant GTPCH deficiency, the optional doses of l-Dopa is 4 to 5mg/kg/day with carbidopa, that is, menesit or 20mg/kg/day with plain l-Dopa, that is, without carbidopa. With these doses the effects sustain more than 20-to 30 years and in some after 30 years of age, the dosis can be reduced slightly. However, at the first step of l-Dopa treatment, there are patients whose response to l-Dopa is not marked or who show aggravation of symptoms, particularly active backward extension of the neck (action retrocollis) or upward derivation of the eye balls (oculogyric crisis) or show involuntary movements such as choreic movements.. For the former patients l-Dopa should be started with small dosis and finally rather higher dosis are necessary. In some administration of tetrahydrobiopterin in addition to l-Dopa is effective. For the latter patients, it is necessary to ...
BioMarin (http://www.biomarinpharm.com/). Phenoptin™ (BH4): BioMarin initiates Phase 3 Clinical Trial of Phenoptin™ for PKU. Novato, CA, April 7, 2005 - BioMarin Pharmaceutical Inc. (Nasdaq and SWX: BMRN) announced today that it has randomized the first patient in its Phase 3 clinical trial of Phenoptin™ (sapropterin hydrochloride), an investigational oral, small molecule therapeutic for the treatment of the genetic disease phenylketonuria (PKU). The company expects to announce data from this trial in the second half of 2005. ...
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Page contains details about two-dimensional (BA)2SnI3(BH4) . It has composition images, properties, Characterization methods, synthesis, applications and reference articles : nano.nature.com
Cerebrospinal Fluid Neopterin in Human Immunodeficiency Virus Type 1 Infection Bruce J. Brew, MB, FRACP, Ravi B. Bhalla, PhD,? Morris Paul, PhD,* H. Gallardo, MS,* Justin C. McArthur, MBBS,S Morton K. Schwartz, PhD,t and &chard W. Price, MD We evaluated cerebrospinal fluid (CSF) concentrations of neopterin, a putative marker of activated macrophages, in 97 subjects infected with human immunodeficiency virus type 1 who had a spectrum of neurological complications. The highest CSF neopterin concentrations occurred in those with neurological opportunistic infections, primary central nervous systems lymphoma, and acquired immunodeficiency syndrome (AIDS)dementia complex. In general, the CSF concentration of neopterin was independent of CSF cell count and blood-brain barrier disruption to albumin. In the patients with AIDS dementia complex, CSF neopterin concentrations correlated with severity of disease and decreased in conjunction with clinical improvement following treatment with zidovudine. ...
And a team of a hydroxypyrimidine antifungal agent sensitivity of the mammogram. - posted in General Discussion: And a team of a hydroxypyrimidine antifungal agent sensitivity of the mammogram. What is an autism spectrum disorder? The relapse histone variant levels in. Museo paso a formar provided based on the medecins ni de cliniques. Your character will continue fishing until your backpack generic tile How is medicine vaginismus treated? and Present Colleges. Long term effect of studies...
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 - ...
Asubio Pharma, one of the group companies of Daiichi Sankyo, has announced an additional indication for the inherited metabolic disease agent Biopten for the treatment of tetrahydrobiopterin responsive hyperphenylalaninemia. Asubios Biopten is said to be a highly pure chemically synthesized form of the tetrahydrobiopterin (BH4) that occurs naturally in the human body. It treats hyperphenylalaninemia (HPA) patients by ameliorating the serum phenylalanine level. Maruho marketed Biopten under a contract that expired at the end of June, 2008. From July 1, 2008 Daiichi Sankyo began marketing Biopten under a contract.. ...
Looking for online definition of GTPCH or what GTPCH stands for? GTPCH is listed in the Worlds largest and most authoritative dictionary database of abbreviations and acronyms
Now, a group of European scientists has discovered new compounds that may help to fight these diseases more effectively. The project was carried out by research groups headed by Maria Paola Costi (University of Modena and Reggio Emilia, Italy), Rebecca Wade (HITS, Heidelberg Institute for Theoretical Studies, Germany) and Paul Michels (De Duve Institute , Belgium). It was supported by the Cassa di Risparmio di Modena Foundation. The research results have been published in the Journal of Medicinal Chemistry.. Trypanosomatids require folates and biopterins. These are reduced by the enzymes dihydrofolate reductase (DHFR) and pteridine reductase (PTR1). When DHFR is inhibited, DNA replication is impaired, resulting in cell death. However in trypanosomatids, PTR1 is overexpressed when DHFR is inhibited, and PTR1 can take on the role of DHFR by reducing folates, ensuring parasite survival. For the treatment of anti-parasitic diseases, it is thus necessary to block two metabolic pathways by ...
Feillet, F; van Spronsen, F J; MacDonald, A; Trefz, F K; Demirkol, M; Giovannini, M; Bélanger-Quintana, A; Blau, N (2010). Challenges and pitfalls in the management of phenylketonuria. Pediatrics, 126(2):333-341.. Blau, N; Bélanger-Quintana, A; Demirkol, M; Feillet, F; Giovannini, M; Macdonald, A; Trefz, F K; van Spronsen, F (2010). Management of phenylketonuria in Europe: Survey results from 19 countries. Molecular Genetics and Metabolism, 99(2):109-115.. Blau, N; Bélanger-Quintana, A; Demirkol, M; Feillet, F; Giovannini, M; MacDonald, A; Trefz, F K; van Spronsen, F J (2009). Optimizing the use of sapropterin (BH(4)) in the management of phenylketonuria. Molecular Genetics and Metabolism, 96(4):158-163.. ...
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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.
Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Chemistry, Medicinal, Pharmacology & Pharmacy, BIOCHEMISTRY & MOLECULAR BIOLOGY, CHEMISTRY, MEDICINAL, Phenylalanine 4-monooxygenase, thioether substrates, S-oxidation, inhibition, computer modelling, CARBOXYMETHYL-L-CYSTEINE, CATALYTIC DOMAIN, HYDROXYLASE, 3-(2-THIENYL)-L-ALANINE, TETRAHYDROBIOPTERIN, SPECIFICITY, MECHANISM ...
MetabolismBiosynthesis of cofactors, prosthetic groups, and carriersRiboflavin, FMN, and FADGTP cyclohydrolase II (TIGR00505; EC 3.5.4.25; HMM-score: 12.4) ...
Dramatic Change in the Tertiary Structure of Giant DNA without Distortion of the Secondary Structure Caused by Pteridine - Polyamine Conjugates ...
Dopa-responsive dystonia (DRD) is a rare inherited dystonia that responds very well to levodopa treatment. Genetic mutations of GTP cyclohydrolase I (GCH1) or tyrosine hydroxylase (TH) are disease-causing mutations in DRD. To evaluate the genotype-phenotype correlations and diagnostic values of GCH1 and TH mutation screening in DRD patients, we carried out a combined study of familial and sporadic cases in Chinese Han subjects. We collected 23 subjects, 8 patients with DRD, 5 unaffected family members, and 10 sporadic cases.
TY - JOUR. T1 - Mechanism of Metal-Independent Hydroxylation by Chromobacterium violaceum Phenylalanine Hydroxylase. AU - Carr, Robert T.. AU - Balasubramanian, Shankar. AU - Hawkins, Paul C.D.. AU - Benkovic, Stephen. PY - 1995/1/1. Y1 - 1995/1/1. N2 - Phenylalanine hydroxylase converts phenylalanine to tyrosine utilizing a tetrahydrobiopterin cofactor. Several key mechanistic questions have yet to be resolved, specifically the identity of the hydroxylating species and the role of the non-heme iron which is present in all of the mammalian PAHs. Recently, we have demonstrated that a bacterial PAH from Chromobacterium violaceum does not require any redox active metal for activity [Carr, R. T., & Benkovic, S. J. (1993) Biochemistry 32, 14132-14138]. To identify the function of iron in the mammalian PAHs, we have undertaken a series of experiments to compare the mechanisms of this metal-independent PAH with the iron-dependent PAH from rat liver. Using [4-2H]phenylalanine as a substrate gave a ...
Surrogate markers including CD4 T cell, viral load estimation and activated immune markers have been identified as having significance in the pathogenesis and prognosis of the HIV infection. But there is limited data on the utility of serum neopterin estimation in HIV infection. This study was aimed at evaluating serum neopterin levels as a marker of predicting the progression of HIV infection and to monitor patients response to antiretroviral therapy. In all one hundred and ninety two (192) HIV infected patients constituting one hundred and four highly active antiretroviral therapy patients (104) and eighty eight (88) highly active antiretroviral therapy naïve patients were recruited from the HIV clinic at the Bomso specialist hospital in the Kumasi metropolis. Venous blood samples were taken and assayed for haematological parameters (Haemoglobin, White blood cell, Red blood cell, Mean cell haemoglobin, Mean cell volume, Haematocrit and Mean cell haemoglobin concentration) , Biochemical ...
TY - JOUR. T1 - Expression of phenylalanine hydroxylase (PAH) in erythrogenic bone marrow does not correct hyperphenylalaninemia in Pahenu2 mice. AU - Harding, Cary. AU - Neff, Mark. AU - Jones, Kelly. AU - Wild, Krzysztof. AU - Wolff, Jon A.. PY - 2003/11. Y1 - 2003/11. N2 - Background: Treatment of many inherited liver enzyme deficiencies requires the removal of toxic intermediate metabolites from the blood of affected individuals. We propose that circulating toxins can be adequately cleared and disease phenotype influenced by enzyme expressed in tissues other than the liver, such as bone marrow. Our specific hypothesis was that phenylalanine hydroxylase (PAH) expressed in bone marrow would lower blood phenylalanine levels in hyperphenylalaninemic Pahenu2 mice, a model of human phenylketonuria (PKU). Methods: Germline-modified marrow PAH-expressing mice were developed using a transgene that contained the mouse liver PAH cDNA under the transcriptional control of a human β-globin promoter. ...
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.. ...
PKU : Phenylketonuria (PKU) is the most frequent inherited disorder of amino acid metabolism (about 1:10,000-1:15,000) and was the first successfully treated inborn error of metabolism. It is inherited in an autosomal recessive manner and is caused by a defect in the enzyme phenylalanine hydroxylase (PAH), which converts the essential amino acid phenylalanine to tyrosine. Deficiency of PAH results in decreased levels of tyrosine and an accumulation of phenylalanine in blood and tissues. Untreated, PKU leads to severe brain damage with intellectual impairment, behavior abnormalities, seizures, and spasticity. The level of enzyme activity differentiates classic PKU (PAH activity |1%) from other milder forms; however, all are characterized by increased levels of phenylalanine (hyperphenylalaninemia). Treatment includes the early introduction of a diet low in phenylalanine. Tetrahydrobiopterin (BH4) is a cofactor of not only PAH, but also of the tyrosine and tryptophan hydroxylases. Approximately 2% of
accuracy of markers was evaluated by the ROC curve analysis. Results: Mean serum neopterin levels were significantly higher in patients with unstable and stable angina pectoris in comparison to control subjects (p,0.05, for both patients groups). Serum NO2-/NO3- values were significantly elevated (p,0.01) in patients with unstable angina and acute myocardial infarction. Serum iNOS were significantly elevated in patients with unstable angina pectoris in comparison to control subjects (p,0.05). TNF- α was significantly elevated in patients with acute myocardial infarction in comparison to patients with stable angina pectoris (p,0.001) and the control group (p,0.01). Serum ADMA values were significantly elevated (p,0.001) in all patient groups. The highest concentration of hsCRP, fibrinogen and leukocytes were noted in patients with acute myocardial infarction, while ESR was significantly higher in patients with unstable angina pectoris. A strong correlation was found between LE and smoking ...
Our results confirm and expand previous observations by others11,12,37 that ACS is a pancoronary condition related to the presence of multiple vulnerable plaques. Inflammation and pancoronary plaque vulnerability appear to be directly related and the results of our study give further support to the importance of systemic and local inflammation in multiple atheromatous plaque disruption. Indeed, neutrophil count, neopterin concentration, and CRP concentration were higher in patients with multiple complex lesions than in those with fewer than three complex stenoses. Our findings provide a pathophysiological basis to recent reports by Goldstein et al,7 Rioufol et al,12 and Asakura et al,37 who observed multiple plaque fissuring in patients with ACS. Goldstein et al7 showed with coronary angiography the existence of additional unstable lesions other than the culprit lesions in 21% of patients with myocardial infarction. Using intravascular ultrasound, Rioufol et al12 found culprit lesion fissuring ...
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Phenylketonuria (PKU) - Pipeline Review, H1 2017 Summary Phenylketonuria (also called PKU), is a rare inherited disorder that causes an amino acid c
Data & statistics on BH inflation rate and the general government budget balance: Sensitivity of projection of the general government budget balance, The long-run implications of population ageing for several macroeconomic variables, government expenditures and the budget-balancing consumption tax rate. The effects are presented as percentage changes in variables from 2007-08 to 2053 under the three population scenarios. These effects reflect a combination of the changes in cohort shares and the general equilibrium effects, especially on the consumption ..., Government approved a plan to combat inflation...
A genetic disorder that, through a deficiency in a liver enzyme, phenylalanine hydroxylase, causes severe mental retardation unless phenylalanine can be largely restricted from the diet until the age of six. Abbreviated to PKU.
Phenylketonuria, also called PKU, is a genetic disorder that increases the levels of phenylalanine in the blood. Phenylalanine is an ...
Nitric oxide (NO) is produced by numerous different cell types, and it is an important regulator and mediator of many processes including smooth muscle relaxation, neurotransmission, and murine macrophage- mediated cytotoxicity for microbes and tumor cells. Although murine macrophages produce NO readily after activation, human monocytes and tissue macrophages have been reported to produce only low levels of NO in vitro. The purpose of this study was to determine if stimulated human mononuclear phagocytes produce inducible nitric oxide synthase (iNOS) mRNA, protein, and enzymatic activity. By reverse transcriptase- polymerase chain reaction (RT-PCR) analysis, we show that human monocytes can be induced to express iNOS mRNA after treatment with lipopolysaccharide (LPS) and/or interferon-gamma (IFN-gamma). By immunofluorescence and immunoblot analyses, we show monocytes and peritoneal macrophages contain detectable levels of iNOS antigen after stimulations with cytokines in vitro. Control monocytes ...
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Phenylalanine hydroxylase deficiency is an autosomal recessive disorder caused by pathogenic variants in the gene PAH. While it is found in many different ethnicities, it is particularly prevalent in Sephardic Jewish, Sicilian, Irish, and Turkish individuals, as well as Caucasians. Pathogenic PAH variants result in loss of function of the phenylalanine hydroxylase enzyme, which breaks down the amino acid phenylalanine. The most severe form of the disease is called phenylketonuria. If untreated, buildup of phenylalanine will result in irreversible brain damage and severe intellectual disability. Treatment involves the removal of phenylalanine from the diet. Even with strict adherence to the treatment, some neurologic deficiencies have been noticed in long-term survivors. Psychological problems, including anxiety, depression, phobias and panic attacks may occur in adults who do not comply well to their treatment. Some patients have a milder form of hyperphenylalaninemia and may tolerate higher ...
A method of mass newborn screening for PKU that is still in use today in some countries. The test involves applying a drop of blood from a heel prick to filter paper, which is sent to the laboratory. Small circles of paper from within the blood spot are punched out and applied to the surface of an agar gel containing the bacterium, Bactilis subtilis, which requires phenylalanine for growth. The gel also contains β-2-thienylalanine, which suppresses bacterial growth by inhibiting the use of phenylalanine by the bacteria. Increasing the local phenylalanine concentration (i.e. from a blood spot from an infant with hyperphenylalaninemia) overcomes the inhibition of growth and a ring of bacterial growth appears around the positive sample within one day. The diameter of the bacterial colony provides an estimate of the concentration of phenylalanine in the sample.. In many countries, the Guthrie test has been overtaken by newer methods such as Tandem Mass Spectrometr. ...

Cerebrospinal fluid neopterin in human immunodeficiency virus type 1 infection.Cerebrospinal fluid neopterin in human immunodeficiency virus type 1 infection.

Urinary neopterin and biopterin levels in patients with AIDS and AIDS-related complex. Lancet 1985;2:51-52 3. Fuchs D, Jaeger H ...
more infohttps://www.docme.ru/doc/1914619/cerebrospinal-fluid-neopterin-in-human-immunodeficiency-v..

Biopterin - WikipediaBiopterin - Wikipedia

Biopterin compounds found within the body include both BH4 and BH2. Biopterin synthesis occurs through two principal pathways; ... Biopterin synthesis disorders are also a cause of hyperphenylalaninemia; phenylalanine metabolism requires BH4 as a cofactor. ... A number of disorders of biopterin regulation exist. Single-gene defects affecting the gene GCH1 block the first step in ... Mouse gene knockout models that block biopterin synthesis completely die shortly after birth due to their inability to produce ...
more infohttps://en.wikipedia.org/wiki/Biopterin

Folate-biopterin transporter family - WikipediaFolate-biopterin transporter family - Wikipedia

The folate-biopterin transporter (FBT) family (TC# 2.A.71) is a distant family within the major facilitator superfamily, most ... As of this edit, this article uses content from "2.A.71 The Folate-Biopterin Transporter (FBT) Family", which is licensed in a ... A related protein in Trypanosoma brucei, ESAGIO, shows weak folate/biopterin transport activity. There are at least 6 ... The probable transport reaction catalyzed by characterized FBT family members is: [folate, biopterin, or AdoMet] (out) + H+ ( ...
more infohttps://en.wikipedia.org/wiki/Folate-biopterin_transporter_family

Biopterin | Springer for Research & DevelopmentBiopterin | Springer for Research & Development

Biopterin gehört, wie die Folate, zur Familie der Pterine. Es ist in seiner biologisch aktiven Form 5,6,7,8-Tetrahydrobiopterin ... Jomaa H. (2019) Biopterin. In: Gressner A.M., Arndt T. (eds) Lexikon der Medizinischen Laboratoriumsdiagnostik. Springer ... Aufgrund der Beteiligung des Biopterin an der NO-Synthasereaktion kommt es bei Entzündungen zu einer Induktion der ... HPLC-basierte Methoden mit fluorimetrischer oder massenspektrometrischer Detektion stehen zur Verfügung, um Biopterin und die ...
more infohttps://rd.springer.com/chapter/10.1007%2F978-3-662-48986-4_569

WikiGenes - biopterin - 2-amino-6-[(1R,2R)-1,2-dihydroxypropyl]-1H...WikiGenes - biopterin - 2-amino-6-[(1R,2R)-1,2-dihydroxypropyl]-1H...

biopterin 2-amino-6-[(1R,2R)-1,2- dihydroxypropyl]-1H.... Synonyms: D-Biopterin, Pterin H B2, AG-D-61696, CHEBI:41183, ... Cerebrospinal fluid biogenic amines and biopterin in Rett syndrome [7].. *We measured monoamine metabolites and biopterin in ... Disease relevance of biopterin. *Hyperphenylalaninemia due to a deficiency of biopterin. A variant form of phenylketonuria [1]. ... Chemical compound and disease context of biopterin. *Neopterin and biopterin CSF levels in tardive dyskinesia after clozapine ...
more infohttps://www.wikigenes.org/e/chem/e/444475.html

Human mononuclear phagocyte inducible nitric oxide synthase (iNOS): analysis of iNOS mRNA, iNOS protein, biopterin, and nitric...Human mononuclear phagocyte inducible nitric oxide synthase (iNOS): analysis of iNOS mRNA, iNOS protein, biopterin, and nitric...

Biopterin, an obligate cofactor of iNOS enzymatic activity, is undetectable in freshly isolated or cultured human monocytes and ... Human mononuclear phagocyte inducible nitric oxide synthase (iNOS): analysis of iNOS mRNA, iNOS protein, biopterin, and nitric ... Human mononuclear phagocyte inducible nitric oxide synthase (iNOS): analysis of iNOS mRNA, iNOS protein, biopterin, and nitric ... Human mononuclear phagocyte inducible nitric oxide synthase (iNOS): analysis of iNOS mRNA, iNOS protein, biopterin, and nitric ...
more infohttp://www.bloodjournal.org/content/86/3/1184?ijkey=b8c98c134f1071d7d1cabc5bea58a4781f795273&keytype2=tf_ipsecsha&sso-checked=true

IL154530D0 - Process for production of biopterin compound 
      - Google PatentsIL154530D0 - Process for production of biopterin compound - Google Patents

biopterin compound. biopterin. compound. Prior art date. 2000-08-31. Application number. IL15453001A. Original Assignee. ... IL154530D0 - Process for production of biopterin compound - Google Patents. Process for production of biopterin compound Info. ... Preparation of L- biopterin JP3137333B2 (en) * 1990-07-21. 2001-02-19. サントリー株式会社. Preparation of tetrahydrobiopterin and enzyme ... Process for production of biopterin compound IL154530A IL154530A (en) 2000-08-31. 2003-02-18. Process for the production of a ...
more infohttps://patents.google.com/patent/IL154530D0/en

6R)-5,6,7,8-TETRAHYDRO-L-BIOPTERIN DIHYDROCHLORIDE - 25 MG6R)-5,6,7,8-TETRAHYDRO-L-BIOPTERIN DIHYDROCHLORIDE - 25 MG

ArtChemicals.com is a certified Green Company, supplying a wide variety of chemicals, tools, accessories, lab equipment, safety equipment, safety supplies, and chemical information. We supply chemicals in pre-set sizes or will custom package to fit your needs and minimize environmental impacts.
more infohttps://www.artchemicals.com/product_p/t3207-25mg.htm

StrateGene - Biopterin Pathway - Pathway Support - PathwaysStrateGene - Biopterin Pathway - Pathway Support - Pathways

... biopterin, and histamine pathways.. What is StrateGene?. StrateGene is a genetic reporting tool that uses AncestryDNA (Version ...
more infohttps://www.seekinghealth.com/strategene-analysis?p=2

B Chronic oral tetrahydrobiopterin treatment in patients with coronary artery disease elevates total biopterin levels but does...B Chronic oral tetrahydrobiopterin treatment in patients with coronary artery disease elevates total biopterin levels but does...

Biopterin levels were measured in plasma at baseline and after the treatment period, and in saphenous vein (SV) and internal ... Conclusion Although absolute BH4 levels in plasma and SV are increased, chronic oral BH4 therapy does not alter biopterin redox ... B Chronic oral tetrahydrobiopterin treatment in patients with coronary artery disease elevates total biopterin levels but does ... B Chronic oral tetrahydrobiopterin treatment in patients with coronary artery disease elevates total biopterin levels but does ...
more infohttps://heart.bmj.com/content/96/Suppl_1/A1.2

biopterin - meddicbiopterin - meddic

Biopterin compounds found within the body include both BH4 and BH2.. Synthesis. Biopterin synthesis occurs through two ... ビオプテリン(biopterin)は、体内で合成される補酵素の一つ。テトラヒドロビオプテリンの酸化分解産物である。 専門用語集 の検索結果 家庭の医学の検索結果 … 1件 ビオプテリン異常症 「ビオプテリン」の使用例を検索する "Lets get up ... チロシン tyrosine (フェニル基の3位にOHを導入) :律速酵素 -チロシン 3-モノオキシゲナーゼ tyrosine 3-monooxygenase, チロシン水酸化
more infohttp://meddic.jp/biopterin

Suspected pterin-4a-carbinolamine dehydratase deficiency : hyperphenylalaninaemia due to inhibition of phenylalanine...Suspected pterin-4a-carbinolamine dehydratase deficiency : hyperphenylalaninaemia due to inhibition of phenylalanine...

... hyperphenylalaninaemia due to inhibition of phenylalanine hydroxylase by tetrahydro-7-biopterin. * Home ... hyperphenylalaninaemia due to inhibition of phenylalanine hydroxylase by tetrahydro-7-biopterin. Publikationstyp:. ... hyperphenylalaninaemia due to inhibition of phenylalanine hydroxylase by tetrahydro-7-biopterin. In: Journal of inherited ... hyperphenylalaninaemia due to inhibition of phenylalanine hydroxylase by tetrahydro-7-biopterin,/dcterms:title, ,dc:contributor ...
more infohttps://kops.uni-konstanz.de/handle/123456789/8022

Profound biopterin oxidation and protein tyrosine nitration in tissues of ApoE-null mice on an atherogenic diet: contribution...Profound biopterin oxidation and protein tyrosine nitration in tissues of ApoE-null mice on an atherogenic diet: contribution...

Profound biopterin oxidation and protein tyrosine nitration in tissues of ApoE-null mice on an atherogenic diet: contribution ... Profound biopterin oxidation and protein tyrosine nitration in tissues of ApoE-null mice on an atherogenic diet: contribution ... Profound biopterin oxidation and protein tyrosine nitration in tissues of ApoE-null mice on an atherogenic diet: contribution ... Animals, Apolipoproteins E, Atherosclerosis, Biopterin, Dietary Fats, Metabolic Clearance Rate, Mice, Mice, Inbred C57BL, Mice ...
more infohttps://www.rdm.ox.ac.uk/publications/342140

GCH1 haplotype determines vascular and plasma biopterin availability in coronary artery disease effects on vascular superoxide...GCH1 haplotype determines vascular and plasma biopterin availability in coronary artery disease effects on vascular superoxide...

We examined the associations between haplotypes of the GCH1 gene, GCH1 expression and biopterin levels, and the effects on ... GCH1 haplotype determines vascular and plasma biopterin availability in coronary artery disease effects on vascular superoxide ... GCH1 Haplotype Determines Vascular and Plasma Biopterin Availability in Coronary Artery Disease ... GCH1 Haplotype Determines Vascular and Plasma Biopterin Availability in Coronary Artery Disease ...
more infohttps://phgkb.cdc.gov/PHGKB/phgHome.action?action=forward&dbsource=huge&id=37259

Plus itPlus it

Biopterin dynamics and effects of BH4 on blood glucose levels in diabetic mice. A-D: BH2 levels and BH4-to-BH2 ratio of liver, ... Biopterin dynamics and effects of BH4 on blood glucose levels in diabetic mice.. In STZ diabetic wild-type mice, the content of ... Biopterin analysis.. Tissues or whole blood of wild-type mice and wild-type mice with STZ-induced diabetes was collected. For ... The organs were weighed, frozen immediately in liquid N2, and then stored at −80°C. Total biopterin, BH4, and BH2 were measured ...
more infohttp://diabetes.diabetesjournals.org/content/62/9/3033

Products in LKT Labs on Thomas ScientificProducts in LKT Labs on Thomas Scientific

Biopterin LKT Labs. Biopterin is an endogenous pterin coenzyme that acts as a cofactor for amino acid hydroxylases that produce ...
more infohttp://www.thomassci.com/nav/manufacturer/lktlabs/0

Regulation of Tetrahydrobiopterin Biosynthesis by Shear Stress | Circulation ResearchRegulation of Tetrahydrobiopterin Biosynthesis by Shear Stress | Circulation Research

Measurements of Biopterin. Measurements of biopterin content were performed using high-performance liquid chromatography (HPLC ... Analysis of reduced forms of biopterin in biological tissues and fluids. Anal Biochem. 1980; 102: 176-188. ... had no effect on the increase in H4B caused by shear and had no effect on the ratio of reduced to oxidized biopterin (Figure 5C ... Diagnosis of dopa-responsive dystonia and other tetrahydrobiopterin disorders by the study of biopterin metabolism in ...
more infohttp://circres.ahajournals.org/content/101/8/830

Browsing University of Texas Patents by TitleBrowsing University of Texas Patents by Title

Lipoidal biopterin compounds  Folkers, Karl A.; Laesecke, Klaus P. (United States Patent and Trademark Office, 1985-10-29) ... The present invention provides lipoidal biopterin and tetrahydrobiopterin compounds of the general structure: ##STR1## wherein ...
more infohttps://repositories.lib.utexas.edu/handle/2152/74529/browse?rpp=20&sort_by=1&type=title&etal=-1&starts_with=L&order=ASC

Tetrahydrobiopterin (BH4)Tetrahydrobiopterin (BH4)

Biopterin Levels, Schizophrenia and Schizoaffective Disorder.. Posted on June 28, 2007. by Dr. Gary Pack ... Miscellaneous: Amines, Biopterin, Brain, Catecholamines, Conduction, Dopamine, l-DOPA, Neurotransmitters, Nitric oxide (NO), ...
more infohttps://www.rainbow.coop/nutritional-library/supplement/tetrahydrobiopterin-bh4/

TCDB » SEARCHTCDB » SEARCH

BT1 biopterin/folate (not methotrexate) transporter. Accession Number:. Q25272. Protein Name:. BT1 aka OrfG. ...
more infohttp://tcdb.org/search/result.php?tc=2.A.71.1.1

Patent US20060249381 - Cellulosic-based resistance domain for an analyte sensor - Google PatentsPatent US20060249381 - Cellulosic-based resistance domain for an analyte sensor - Google Patents

... biopterin; c-reactive protein; camitine; carnosinase; CD4; ceruloplasmin; chenodeoxycholic acid; chloroquine; cholesterol; ...
more infohttp://www.google.com/patents/US20060249381?dq=6,304,975

Patent US20060020189 - Transcutaneous analyte sensor - Google PatentsPatent US20060020189 - Transcutaneous analyte sensor - Google Patents

... biopterin; c-reactive protein; carnitine; carnosinase; CD4; ceruloplasmin; chenodeoxycholic acid; chloroquine; cholesterol; ...
more infohttp://www.google.com/patents/US20060020189?dq=5311516

Plus itPlus it

Using HPLC, we determined that the total biopterin pool (BH4 + BH2 + biopterin), but not the BH2 + biopterin pool, was ... Determination of total biopterin levels by HPLC.. Lung biopterin content was measured by HPLC analysis and a differential ... biopterin] were measured by HPLC with an acid extraction. Oxidized biopterins (BH2 + biopterin) were measured by HPLC with an ... biopterin + BH4 + dihydrobiopterin (BH2)] and the alkaline extraction (BH2 + biopterin). A 5-μm C-18 reverse chromatography ...
more infohttp://ajplung.physiology.org/content/295/6/L979
  • Biopterin gehört, wie die Folate, zur Familie der Pterine. (springer.com)
  • The folate-biopterin transporter (FBT) family (TC# 2.A.71) is a distant family within the major facilitator superfamily, most closely related to drug resistance permeases. (wikipedia.org)
  • The probable transport reaction catalyzed by characterized FBT family members is: [folate, biopterin, or AdoMet] (out) + H+ (out) → [folate, biopterin, or AdoMet] (in) + H+ (in) The FBT family includes functionally characterized members from protozoa, cyanobacteria and plants. (wikipedia.org)
  • Functionally characterized members of the family include FT1, the major folate transporter, and BT1, the biopterin/folate transporter and AdoMetT1, the major S-adenosylmethionine uptake porter. (wikipedia.org)
  • A related protein in Trypanosoma brucei, ESAGIO, shows weak folate/biopterin transport activity. (wikipedia.org)
  • As of this edit, this article uses content from "2.A.71 The Folate-Biopterin Transporter (FBT) Family", which is licensed in a way that permits reuse under the Creative Commons Attribution-ShareAlike 3.0 Unported License, but not under the GFDL. (wikipedia.org)
  • With StrateGene you can quickly learn about potential issues by overlaying your SNPs or those of your patients onto the Pathway Planners covering the important folate, methionine, transsulfuration, biopterin, and histamine pathways. (seekinghealth.com)
  • Conclusion Although absolute BH4 levels in plasma and SV are increased, chronic oral BH4 therapy does not alter biopterin redox status (BH4:BH2 ratio) in either plasma or vascular tissue. (bmj.com)
  • Biopterin levels were measured in plasma at baseline and after the treatment period, and in saphenous vein (SV) and internal mammary artery (IMA) tissue collected at the time of surgery. (bmj.com)