SEARCH · Search PubMed

Results for “PTERINS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 181 records · Page 10Linked to original sources

PubMed2003

Physarum polycephalum expresses a dihydropteridine reductase with selectivity for pterin substrates with a 6-(1', 2'-dihydroxypropyl) substitution.

Physarum polycephalum is one of few non-animal organisms capable of synthesizing tetrahydrobiopterin from GTP. Here we demonstrate developmentally regulated expression of quinoid dihydropteridine reductase (EC 1.6.99.7), an enzyme required for recycling 6,7-[8H]-dihydrobiopterin. Physarum also expresses phenylalanine-4-hydroxylase activity, an enzyme that depends on dihydropteridine reductase. The 24.4 kDa Physarum dihydropteridine reductase shares 43% amino acid identity with the human protein. A number of residues important for function of the mammalian enzyme are also conserved in the Physarum sequence. In comparison to sheep liver dihydropteridine reductase, purified recombinant Physarum dihydropteridine reductase prefers pterin substrates with a 6-(1', 2'-dihydroxypropyl) group. Our results demonstrate that Physarum synthesizes, utilizes and metabolizes tetrahydrobiopterin in a way hitherto thought to be restricted to the animal kingdom.

Amino Acid Sequence↗

PubMed1984

Pterins and the regulation of lymphocyte activation on the mode of xanthopterin action.

Some intermediates of pterin anabolism amplify the lectin-induced lymphocyte stimulation while the catabolites xanthopterin and isoxanthopterin terminate their proliferation (Ziegler, I. et al., Cancer Res. 43, 5356 (1983). In the present investigation, we analysed the effect of xanthopterin on total RNA synthesis and on DNA synthesis in both concanavalin A-stimulated lymphocytes and in the lymphoblastoid cell line L 1210. The time courses at various inhibitor concentrations indicated that xanthopterin inhibits RNA synthesis prior to DNA synthesis. Further analysis of the RNA species was performed by double-labeling and subsequent polyacrylamide-gel electrophoresis. Pulse and pulse-chase experiments revealed that an inhibition of 45 S pre-RNA is closer to the target of xanthopterin inhibition than is DNA synthesis.

Animals↗

PubMed1992

Approaches to the preparation of 6- and 7-methyl-8-substituted pterins: Part 1. The effect of reaction conditions on isomer distribution and a novel approach to isomer separation.

A new approach to the preparation of 6- and 7-methyl-8-alkylpterins is reported. This procedure relies primarily on the separation of the isomers due to their different propensities to form adducts with hydrogensulfite. The primary synthesis of 6-methyl-8-propylpterin was achieved by the condensation of 2,5-diamino-6-(propylamino)pyrimidin-4(3H)- one with pyruvic aldehyde in the presence of NaHSO3 at pH 4. This results in a solid product which was found to be > 98% pure 6-isomer in the form of the HSO3- adduct. Further treatment by a simple procedure gave the final product as the pterin hydrochloride greater than 99.5% isomer pure. The 7-methyl isomer was obtained from the filtrate of the primary synthesis by a cation exchange chromatographic procedure, again exploiting the different propensities of the two isomers to form adduct. The effect of reaction conditions and the nature of the 8-substituent on the proportions of the isomeric products produced by the above condensation reaction was investigated by a series of small scale syntheses. It was found that the proportion of the two isomeric products was dependent on the size of the 8-substituent and, to a lesser extent, the pH of the reaction mixture. For large 8-substituents such as n-propyl, isopropyl and 2-hydroxyethyl, 6-methyl isomer was the predominant product under all conditions. The presence of HSO3 [symbol: see text] did not generate any significant regioselective effect toward further formation of 6-isomer but had either negligible effect on the product distribution or increased the amount of 7-isomer formed. For the small methyl 8-substituent, the major product in the absence of HSO3 [symbol: see text] was found to be 7-isomer at all pH values. However, in the presence of HSO3 [symbol: see text] the major product became the 6-isomer. A 1H-NMR study of the nature of pyruvic aldehyde in acidic water solution is reported which shows that pyruvic aldehyde exists primarily as the monohydrated geminal ketodiol with a lesser proportion of the bishydrated vicinal diol. No free aldehyde was observed by 1H-NMR. The implications of these findings and the product distribution experiments are discussed in relation to the mechanism of the reaction and the role of HSO3 [symbol: see text] within this mechanism.

Hydrogen-Ion Concentration↗

PubMedDate not supplied

Reactivity of conjugated and unconjugated pterins with singlet oxygen (O2(1Deltag)): physical quenching and chemical reaction.

Pterins (PTs) belong to a class of heterocyclic compounds present in a wide range of living systems. They participate in relevant biological functions and are involved in different photobiological processes. We have investigated the reactivity of conjugated PTs (folic acid [FA], 10-methylfolic acid [MFA], pteroic acid [PA]) and unconjugated PTs (PT, 6-hydroxymethylpterin [HPT], 6-methylpterin [MPT], 6,7-dimethylpterin [DPT], rhamnopterin [RPT]) with singlet oxygen (1O2) in aqueous solutions, and compared the efficiencies of chemical reaction and physical quenching. The chemical reactions between 1O2, produced by photosensitization, and PT derivatives were followed by UV-visible spectrophotometry and high-performance liquid chromatography, and corresponding rate constants (k(r)) were evaluated. Whenever possible, products were identified and quantified. Rate constants of 1O2 total quenching by the PT derivatives investigated were obtained from steady-state 1O2 luminescence measurements. Results show that the behavior of conjugated PTs differs considerably from that of unconjugated derivatives, and the mechanisms of 1O2 physical quenching by these compounds and of their chemical reaction with 1O2 are discussed in relation to their structural features.

Kinetics↗

PubMed1978

Carotenoid and pterin pigment localization in fish chromatophores.

The classical sulfuric acid method for the histochemical detection of carotenoids has been adapted to give a reliable cytological localization of these compounds in fish chromatophores. This procedure consists mainly in fixing skin fragments in glutaraldehyde and dehydrating in a 50% solution of glycerin followed by exposure to air. It is essential that the preparation permit direct contact of the sulfuric acid with the pigment cells. Under these conditions, carotenoid containing cells stain green or blue. When associated with the extraction of the carotenoids by acetone, the procedure permits the distinction between pterin and carotenoid in fish chromatophores.

Acetone↗

PubMed1976

[Pterin-protein complex and ferredoxin as possible components of a molecular complex in photosystem I].

Properties are studied of pterin-protein complex (PPC), possible precursor of ferredoxin in electrone transport chain PS-I. PPC is shown to form chelate complex with Fe ions which are capable to activate the process of light reduction of NADP+ by chloroplasts in the absence of ferrodoxin. A possibility of dark reduction of NADP+ with the participation of light pre-activated PPC is found. Two-step scheme of electrone transport from P700 to ferredoxin is supposed. The data obtained indicate that one of sites of electrone transport into interior part of tilakoid is located on the reduction side of PS-I. An additional possibility of NADP+ reduction with the participation of PPC-Fe in vivo is suggested.

Chloroplasts↗

PubMed1983

Participation of pterins in the control of lymphocyte stimulation and lymphoblast proliferation.

Biopterin accumulation had been demonstrated as the result of normal and, especially, of malignant hemopoietic cell proliferation (Ziegler, I. et al. Blut, 44: 231-240, and 261-270, 1982). Among 13 major intermediates of pterin metabolism and two lumazines, xanthopterin (but not dihydroxanthopterin) was found to inhibit cell proliferation (half-maximum inhibition at 1.8 X 10(-5) M) during concanavalin A-induced lymphocyte activation in pre-stimulated lymphocytes and in a lymphoid cell line grown in continuous culture (LS-2). LS-2 cells exposed to maximum inhibitor concentrations largely maintained the initial thymidine incorporation rate for about 40 hr but failed to enter logarithmic growth. Isoxanthopterin inhibition was found only in serum-free medium, since it is trapped by the alpha-acid glycoprotein present in the serum. The reduced biopterin derivatives, sepiapterin, dihydrobiopterin, and tetrahydrobiopterin, are costimulators during concanavalin A-induced lymphocyte activation. Their costimulatory effect follows an optimum curve and peaks at 1.5 to 3 X 10(-5) M. It is highest at the suboptimal and supraoptimal concanavalin A concentration. The D-erythro isomer dihydroneopterin was inactive. The results indicate that the anabolic-reduced biopterin derivatives are not simply lymphocytic products, but, in combination with the catabolites xanthopterin and isoxanthopterin, they also participate in the regulation of lymphocyte activation. Hence, they fulfill the criteria for lymphokines.

Animals↗

PubMed1978

Regional and subcellular distribution and some factors in the regulation of reduced pterins in rat brain.

We have studied the regional and subcellular distribution, functional role, and pharmacology of quinoid dihydropterin reductase (QDPR) and endogenous reduced pterins (PH4) subserving tyrosin hydroxylase (TOH) and tryptophan hydroxylase in the rat brain. There is a significant correlation between the regional distribution of PH4 and TOH but not between PH4 and tryptophan hydroxylase or between either TOH or tryptophan hydroxylase and QDPR. This suggests that a major portion of PH4 is associated with the biosynthetic activity of brain catecholaminergic systems. The regional and subcellular distribution of QDPR was inconsistent with a regulatory function for QDPR in monoamine synthesis. In vitro measures of PH4, TOH, and synaptosomal dopamine (DA) and serotonin synthesis in the striate cortex of untreated animals and animals subjected to neurotoxin or electrolytic lesions of the dorsal raphe or substantia nigra exhibit significant covariation of PH4 with synaptosomal DA but not serotonin synthesis and a significant partial correlation of PH4 with DA synthesis. The subcellular distribution of PH4 in the striatum demonstrates an association of PH4 with the biosynthetic function of dopaminergic nerve terminals. Reserpine and d-amphetamine in vivo elicited an increase and decrease, respectively, in striatal PH4 paralleling induced changes in synaptosomal DA synthesis. Other drugs altering central catecholaminergic function did not alter striatal PH4 levels significantly. The data suggest that 1) a major portion of total PH4 (as much as 90% in the striatum) is related to the function of catecholaminergic rather than serotonergic systems, 2) PH4 levels is a determinant of the velocity of DA synthesis and 3) PH4 levels are altered by some psychoactive drugs in association with changes in synaptosomal catecholamine biosynthetic rates.

Animals↗

PubMed1983

Urinary excretion of pterins in tumor-bearing patients.

In a group of 14 individuals without tumor disease and 125 patients with verified malignant tumors we checked the applicability of determination of the pterins concentration in urine by the procedure described by RAO et al. [3]. In total of 242 examinations were performed. The results were compared with the thin-layer chromatography and on the basis of these comparisons the method was modified. Correlation of the clinical conclusion and the values of tests was obtained in 76% of cases. In patients with undoubtedly persisting tumors the correlation was found in 73%, in a group of patients with the leukemia and lymphomas in 97%, with mammary carcinoma in 81%. Evaluation made in these patients prior to the chemotherapy initiation correlated in 100%. This simple test offers a possibility of the use in differential diagnosis of malignant process or in the course of the screening.

Adolescent↗

PubMed1989

Modulation of interleukin 2 high-affinity binding by lymphocyte-derived tetrahydrobiopterin: pterins as potential participants in the control of interleukin 2 receptor assembly.

In this report, we have examined whether (6R)-tetrahydrobiopterin (H4biopterin) modulates the binding of interleukin 2 to high-affinity sites of the cloned mouse cytotoxic T-lymphocyte clone CTLL-2. Scatchard plot analysis of the equilibrium binding data reveals increased affinity when the cells are exposed simultaneously to interleukin 2 and to the pterin. The Kd values are statistically significantly reduced from 1.4 x 10(-11) M to 0.78 x 10(-11) M interleukin 2. The dissociation kinetics of the ligand were followed at 4 degrees C after equilibrium binding under high-affinity conditions (1.2 x 10(-10) M interleukin 2). In the presence of H4 biopterin, the dissociation rate constant (k-1) decreases from 6.2 x 10(-3) min-1 to 3.0 x 10(-3) min-1 and the half-time for dissociation increases from 106.8 min to 218.0 min. As a third approach interleukin 2 was bound to the surface of cells under high-affinity conditions by incubation in the cold and the internalization kinetics upon warming were determined. Sigmoidal-shaped kinetics of endocytosis in control cells indicate that the internalization rates increase only gradually. The presence of H4 biopterin causes an apparent immediate transition from higher-order kinetics to a linear response so that maximum internalization rates are reached immediately upon warming. The data show that lymphocyte-derived H4 biopterin in vitro at concentrations ranging from 2-8 x 10(-7) M modulates interleukin 2 high-affinity binding and that H4 biopterin potentially participates in the control of interleukin 2 receptor assembly.

Binding Sites↗

PubMed1995

Characterization of the human PCBD gene encoding the bifunctional protein pterin-4 alpha-carbinolamine dehydratase/dimerization cofactor for the transcription factor HNF-1 alpha.

The human pterin-4 alpha-carbinolamine dehydratase (PCD)/dimerization cofactor for the transcription factor HNF-1 alpha is a bifunctional protein proposed to be involved in entirely different biochemical functions. We previously established the complete amino acid sequence for the human liver PCD and subsequently isolated its corresponding cDNA. Using this cDNA as a probe, we isolated and determined the complete nucleotide sequence and flanking regions of the single human PCBD gene. The protein coding region of the gene is about 5 kb in length and contains 4 exons. We also defined the messenger RNA 5'-end by reverse transcription of the cap structure, thus allowing to analyze the promoter organization. Within the 5'-flanking sequence, potential regulatory regions include consensus binding sites for transcription factor Sp1, an AP-1, and several AP-2 binding sites; however, the 5' upstream region lacks both a proximal TATA and CAAT box promoter element.

Amino Acid Sequence↗

PubMed1994

Chromosomal location of two human genes encoding tetrahydrobiopterin-metabolizing enzymes: 6-pyruvoyl-tetrahydropterin synthase maps to 11q22.3-q23.3, and pterin-4 alpha-carbinolamine dehydratase maps to 10q22.

Tetrahydrobiopterin (BH4) is the redox cofactor for the aromatic amino acid hydroxylases such as phenylalanine hydroxylase. At least five enzymes are known to be involved in BH4 biosynthesis and regeneration. A deficiency in several of the BH4 metabolic enzymes causes variant types of hyperphenylalaninemias in man. Recently, we cloned and expressed the human cDNAs for two of the BH4 enzymes, the 6-pyruvoyl-tetrahydropterin synthase and the pterin-4 alpha-carbinolamine dehydratase (gene symbols PTS and PCD/DCOH, respectively). In this report, we localized the two genes on the human chromosomes by in situ hybridization. The PTS gene was mapped to the chromosomal region 11q22.3-q23.3, and the PCD/DCOH gene was mapped to the 10q22 band of the genome.

Alcohol Oxidoreductases↗

PubMed2000

Hyperphenylalaninemia and 7-pterin excretion associated with mutations in 4a-hydroxy-tetrahydrobiopterin dehydratase/DCoH: analysis of enzyme activity in intestinal biopsies.

Hyperphenylalaninemia, which can cause neurological disorders and mental retardation, results from a mutation in phenylalanine hydroxylase or an enzyme required for biosynthesis or regeneration of its cofactor, tetrahydrobiopterin. The hyperphenylalaninemia variant primapterinuria is characterized by the excretion of 7-biopterin (primapterin). This disorder is thought to be due to a deficiency of 4a-hydroxy-tetrahydrobiopterin dehydratase (pterin-4a-carbinolamine dehydratase), but a lack of tissue activity has not been directly demonstrated. The five mutations so far recognized in patients with primapterinuria are associated with either a single amino acid change or a premature stop codon. Only C81R has been successfully expressed in soluble form, and was found to have 40% of normal activity. Tissues which could be obtained by minimally invasive procedures were analyzed for dehydratase activity. None was detected in normal human white cells or fibroblasts. However, activity was found in intestine of rat, dog, pig, and particularly humans where it was only eight times lower than in liver. Distribution along the length and across the wall of small intestine was relatively uniform. Moreover, the dehydratases from human liver and intestinal mucosa have identical kinetic properties. A biopsy of duodenal mucosa from a patient with homozygous E96K dehydratase had activity of 55 nmol. min(-1)g(-1) mucosa compared to 329 +/- 32 nmol. min(-1)g(-1) tissue in controls (n = 12). The sixfold lower tissue activity of the E96K mutant alone may not be sufficient to account for the biochemical symptoms of primapterinuria in this patient. However, accumulation of a 4a-hydroxy-tetrahydrobiopterin degradation product (a side-chain cyclic adduct), which has been observed in vitro and appears to be a dehydratase inhibitor, may further exacerbate the problem.

Adolescent↗

PubMed1999

Immunohistochemical localisation of pterin-4alpha-carbinolamine dehydratase in rat peripheral organs.

The bifunctional protein PCD/DCoH is both a pterin-4alpha-carbinolamine dehydratase (PCD) involved in the recycling of tetrahydrobiopterin (BH4) and a dimerisation cofactor (DCoH) of the hepatic nuclear factor 1alpha (HNF-1alpha). An antiserum raised against rat PCD/DCoH was used to localise the protein in peripheral organs. In liver, all the hepatocytes but not the other cell types are immunoreactive. In kidney, the protein is prevalent in the proximal and distal convoluted tubules. In adrenals, all the cells of the medulla are labelled. Positive nerve cells occur in myenteric ganglia of the whole gastrointestinal tract and in the intestinal submucous ganglia. Many positive endocrine cells are present in the epithelium. The immunoreactivity is either cytoplasmic (hepatocytes, convoluted tubules of the kidney and part of the gastrointestinal endocrine cells) or prominently nuclear (kidney collecting tubules, adrenals, intestinal neural plexuses and part of the gastrointestinal endocrine cells). Our results show that PCD/DCoH is present in cells expressing enzymes that use BH4 as a cofactor and/or HNF-1alpha. In addition, PCD/DCoH is present in other cells, for example, neurons in the submucosal plexus. This fact and the prominent nuclear immunoreactivity found in all the positive cells derived from the neural crests argue in favour of a new, still unknown function for the protein.

Adrenal Cortex↗

PubMed1987

The molybdenum-pterin binding protein is encoded by a multigene family in Clostridium pasteurianum.

There are three variants of the molybdenum-pterin binding protein (Mop) encoded by three distinct genes in Clostridium pasteurianum. Nucleotide sequence analysis shows that the three mop genes have greater than 90% homology at the nucleotide level. Upstream from the coding region of each mop gene are potential promoter consensus sequences. Analysis of Mop purified from cells grown under nitrogen-fixing conditions indicates all three genes are expressed. Sequence analysis of the three mop genes and the gene products predicts that there are 10 amino acid replacements among the family. The amino acid replacements are chemically conservative accounting for the co-purification of the three variants of Mop. Protein chemistry data suggest the possibility that glutamic acid residues in Mop may be modified in vivo.

Amino Acid Sequence↗

PubMed2005

Photodynamic effects of a novel pterin derivative on a pancreatic cancer cell line.

6-Formylpterin (6FP) has the potential to produce singlet oxygen (1O2) under UV-A radiation. In order to apply this potential to anti-cancer photodynamic therapy (PDT), we prepared a novel variant of 6FP, 2-(N,N-dimethylaminomethyleneamino)-6-formyl-3-pivaloylpteridine-4-one (6FP-tBu-DMF), and examined its photodynamic effects on a pancreatic cancer cell line, Panc-1 cells. The study using laser scanning confocal microscopy showed that the drug uptake, the 1O2 generation, and cell death were observed in the 6FP-tBu-DMF-treated cells, while these phenomena were not observed in the 6FP-treated cells. The MTT assay also showed the decrease in cell viability only in the 6FP-tBu-DMF-treated cells. Since 6FP and 6FP-tBu-DMF generate 1O2 to the same extent under UV-A radiation in aqueous solutions, these results indicated that the differences in the photodynamic effects between 6FP and 6FP-tBu-DMF were entirely attributed to the differences in the cell permeability between them. The development of cell permeable pterin derivatives has the potential for application in PDT.

Cell Line, Tumor↗

PubMed1999

Overexpression of pterin-4a-carbinolamine dehydratase/dimerization cofactor of hepatocyte nuclear factor 1 in human colon cancer.

Pterin-4a-carbinolamine dehydratase (PCD) is a bifunctional protein also known as DCoH (dimerization co-factor of hepatocyte nuclear factor 1 (HNF1)). PCD/DCoH modulates the DNA binding specificity of HNF1, thus acting on its transcriptional activity. In addition, it participates in the recycling of tetrahydrobiopterin (BH(4)), an essential cofactor of several metabolic reactions. We investigated colorectal tumors and colorectal tumor cell lines as compared to normal colon samples in search of a potential differential expression of PCD/DCoH. Immunohistochemistry was conducted on 20 human colorectal tumors and 20 normal samples using a specific polyclonal antibody. Immunoblotting and RT-PCR analysis for PCD/DCoH and HNF1 were also performed on both human tissues and CACO-2 and HT-29 cell lines. All of the 20 tumors and both colon cancer cell lines presented a strong and widespread immunoreactivity for PCD/DCoH, contrasting with the absence of expression in the normal epithelia. We thus report the massive overexpression of PCD/DCoH in colon tumors, which is in striking contrast with the absence of staining in normal counterparts. The sharp contrast in the expression of a modulator of transcriptional activity between tumoral and normal cells may have a physiopathological role. PCD/DCoH could potentially be a new marker of malignant colon cells in vivo.

Adenocarcinoma↗

PubMed1988

Primapterin, anapterin, and 6-oxo-primapterin, three new 7-substituted pterins identified in a patient with hyperphenylalaninemia.

Three unknown compounds present in the urine of a patient with mild hyperphenylalaninemia were identified to be L-erythro-7-iso-biopterin, D-erythro-7-iso-neopterin, and L-erythro-6-oxo-7-iso-biopterin. The newly identified pterins were named primapterin, anapterin, and 6-oxo-primapterin, respectively. Primapterin and anapterin are present in very low concentrations in every human urine, as well as in the liver of man and mouse, whereas 6-oxo-primapterin was detected in the patient's urine only. Substantial amounts of primapterin were excreted in the patient described. The metabolic origin of primapterin and anapterin is still obscure.

Animals↗