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The Biochemical Journal Mar 1986The oxidation of 4,5-diaminopyrimidin-6(1H)-one, 5,6,7,8-tetrahydropteridin-4(3H)-one, its 6-methyl and cis-6,7-dimethyl derivatives, and 6-methyl- and...
The oxidation of 4,5-diaminopyrimidin-6(1H)-one, 5,6,7,8-tetrahydropteridin-4(3H)-one, its 6-methyl and cis-6,7-dimethyl derivatives, and 6-methyl- and cis-6-7-dimethyl-5,6,7,8-tetrahydropterins, by horseradish peroxidase/H2O2 is enzymic and follows Michaelis-Menten kinetics, and its Km and kcat. values were determined. This oxidation of 5,6,7,8-tetrahydropterins produces quinonoid dihydropterins of established structure, and they are known to be specific substrates for dihydropteridine reductase. By analogy the peroxidase/H2O2 oxidation of the 5,6,7,8-tetrahydropteridin-4(3H)-ones should produce similar quinonoid dihydro species. The quinonoid species derived from 5,6,7,8-tetrahydropteridin-4(3H)-one and its 6-methyl and cis-6,7-dimethyl derivatives are shown to be viable substrates for human brain dihydropteridine reductase, and apparent Km and Vmax. values are reported.
Topics: Brain; Dihydropteridine Reductase; Horseradish Peroxidase; Humans; Kinetics; NADH, NADPH Oxidoreductases; Oxidation-Reduction; Peroxidases; Pteridines; Pterins; Pyrimidines; Structure-Activity Relationship; Substrate Specificity
PubMed: 3718470
DOI: 10.1042/bj2340335 -
Cancer Research Apr 1982A glycoprotein was selectively enriched in the supernatant (Fraction b) obtained by alcohol and trichloroacetic acid fractionation of digitonin extracts from blood of...
A glycoprotein was selectively enriched in the supernatant (Fraction b) obtained by alcohol and trichloroacetic acid fractionation of digitonin extracts from blood of patients with neoplastic diseases and of control subjects. Subsequent chromatography with concanavalin A:Sepharose separated a concanavalin A-reactive fraction from a concanavalin A-nonreactive one. In sodium dodecyl sulfate gel electrophoresis, the fractions from both malignant origin as well as control subjects appeared as single bands showing the same mobility. They were identical with the band obtained from commercial alpha 1-acid glycoprotein. In Fraction b of malignant origin, greatly increased amounts of the alpha 1-acid glycoprotein from malignant cases (AGPM) were found as compared to alpha 1-acid glycoprotein from controls (AGPC). Furthermore, AGPC had a higher glycine content than did AGPM. The electrofocusing pattern of AGPM showed additional bands between pH 3.7 and 4.4, whereas AGPC and commercial alpha 1-acid glycoprotein focused between pH 3.2 and 3.8. In contrast to AGPC and to a commercial alpha 1-acid glycoprotein, AGPM is characterized by a chromophoric group with maximal absorbance at 400 nm. It could be detached by treatment with 6 M guanidine hydrochloride thus indicating a noncovalent binding. The spectral data on the separated chromophore at pH 0.5 agreed with that of a 6,7-substituted pteridine. After detachment with reducing agents, a pteridine in its 7,8-dihydro form was indicated by spectral analysis.
Topics: Amino Acids; Carrier Proteins; Chromogenic Compounds; Concanavalin A; Electrophoresis, Polyacrylamide Gel; Humans; Molecular Weight; Neoplasms; Orosomucoid; Pteridines
PubMed: 7060026
DOI: No ID Found -
The Biochemical Journal Nov 1994Physarum polycephalum, an acellular slime mould, serves as a model system to study cell-cycle-dependent events since nuclear division is naturally synchronous. This...
Physarum polycephalum, an acellular slime mould, serves as a model system to study cell-cycle-dependent events since nuclear division is naturally synchronous. This organism was shown to release isoxanthopterin which is structurally related to tetrahydrobiopterin, a cofactor of aromatic amino acid hydroxylases and of nitric oxide synthases (NOSs) (EC 1.14.13.39). Here, we studied Physarum pteridine biosynthesis in more detail and found that high amounts of tetrahydrobiopterin are produced and NOS activity is expressed. Physarum pteridine biosynthesis is peculiar in as much as 7,8-dihydroneopterin aldolase (EC 4.1.2.25), an enzyme of folic acid biosynthesis usually not found in organisms producing tetrahydrobiopterin, is detected in parallel. NOS purified from Physarum depends on NADPH, tetrahydrobiopterin and flavins. Enzyme activity is independent of exogenous Ca2+ and is inhibited by arginine analogues. The purified enzyme (with a molecular mass of 130 kDa) contains tightly bound tetrahydrobiopterin and flavins. During the synchronous cell cycle of Physarum, pteridine biosynthesis increases during S-phase whereas NOS activity peaks during mitosis, drops at telophase and peaks again during early S-phase. Our results characterize Physarum pteridine biosynthesis and NOS and suggest a possible link between NOS activity and mitosis.
Topics: Amino Acid Oxidoreductases; Animals; Cell Cycle; NADP; Nitric Oxide Synthase; Physarum polycephalum; Pteridines
PubMed: 7528004
DOI: 10.1042/bj3040105 -
Applied Microbiology and Biotechnology Jun 2016Pterin deaminase is an amidohydrolase enzyme hydrolyzing pteridines to form lumazine derivatives and ammonia. The enzyme captured the attention of scientists as early as... (Review)
Review
Pterin deaminase is an amidohydrolase enzyme hydrolyzing pteridines to form lumazine derivatives and ammonia. The enzyme captured the attention of scientists as early as 1959 and had been patented for its application as an anticancer agent. It is ubiquitously present in prokaryotes and has been reported in some eukaryotes such as honey bee, silkworm and rats. The enzyme has been observed to have a spectrum of substrates with the formation of respective lumazines. The role of the substrates of the enzyme in various metabolic pathways warrants a significant role in the biological activity of both prokaryotes and eukaryotes. Even though the functions of the enzyme have been explored in prokaryotes, their niche in the eukaryotic system is not clear. There is very few information on the structural and functional properties of the enzyme. This review has been congregated to emphasize the significance of pterin deaminase and analyzes the lacunae in understanding the biological characters of the enzyme.
Topics: Amidohydrolases; Aminohydrolases; Animals; Biopterins; Eukaryotic Cells; Prokaryotic Cells; Pteridines
PubMed: 27094187
DOI: 10.1007/s00253-016-7513-9 -
Die Pharmazie Mar 1966
Review
Topics: Allantoin; Caffeine; Folic Acid; Heterocyclic Compounds; Methylation; Oxidation-Reduction; Pteridines; Purines; Pyrimidines; Theobromine
PubMed: 4863579
DOI: No ID Found -
Nucleosides, Nucleotides & Nucleic Acids 2004A general synthetic approach to various isoxanthopterin-nucleosides starting from 6-methyl-2-methylthio-4(3H),7(8H)-pterdinedione (1) has been developed. Ribosylation...
A general synthetic approach to various isoxanthopterin-nucleosides starting from 6-methyl-2-methylthio-4(3H),7(8H)-pterdinedione (1) has been developed. Ribosylation with 1-O-acetyl-2,3,5-tri-O-benzoyl-beta-D-ribofuranose via the silyl-method led to 2 and reaction with 1-chloro-2-deoxy-3,5-di-O-p-toluoyl-alpha-D-ribofuranose using the DBU-method afforded 28. Protection of the amide function at O4 by benzylation to 5 and by a Mitsunobu reaction with 2-(4-nitrophenyl)ethanol to 29 gave soluble intermediates which can be oxidized to the corresponding 2-methylsulfonyl derivatives 8 and 30, respectively. Nucleophilic displacement reactions of the highly reactive 2-methylsulfonyl functions by various amines proceeded under mild conditions to isoxanthopterin-N8-ribo- (11-17) and 2'-deoxyribomucleosides (31-33). Debenzylation can be achieve by Pd-catalyzed hydrogenation (9 to 19) and cleavage of the npe-protecting group (31, 32 to 34, 35) works well with DBU by beta-elimination.
Topics: Nucleosides; Pteridines
PubMed: 15043136
DOI: 10.1081/ncn-120027817 -
Bioorganic & Medicinal Chemistry Letters Feb 2005From compound library screening using an HCV NS5B RNA-dependent RNA polymerase enzymatic assay, we identified a pteridine hit compound with an IC(50) of 15 microM. Our...
From compound library screening using an HCV NS5B RNA-dependent RNA polymerase enzymatic assay, we identified a pteridine hit compound with an IC(50) of 15 microM. Our SAR studies were focused on the different groups at the 6- and 7-positions, substitutions at the 4-position, and replacement of N(1) or N(3) with carbon in the pteridine ring. We found that NH or OH at 4-position is critical for the inhibitory activity. Furthermore, a hydrophobic substituent at the 4-position may help compounds permeate through the cell membrane.
Topics: Antiviral Agents; Hepacivirus; Humans; Inhibitory Concentration 50; Pteridines; RNA-Dependent RNA Polymerase; Replicon; Structure-Activity Relationship; Viral Nonstructural Proteins
PubMed: 15664835
DOI: 10.1016/j.bmcl.2004.11.028 -
Biochemical Pharmacology Feb 1974
Comparative Study
Topics: Animals; Cytidine; Diuretics; Eukaryota; Linoleic Acids; Oleic Acids; Pteridines; Tetrahymena pyriformis; Triamterene
PubMed: 4207496
DOI: 10.1016/0006-2952(74)90207-x -
Biochemical Genetics Feb 1989The relationship between high dietary levels of aromatic amino acid and regulation of pteridines in Drosophila eyes was examined by measuring changes in pool levels of...
The relationship between high dietary levels of aromatic amino acid and regulation of pteridines in Drosophila eyes was examined by measuring changes in pool levels of six pterins in the wild type and mutants and amino acid pool levels in flies that carry mutations for pteridine biosynthesis. The effect upon relative viability and developmental times was also analyzed; relative viability was affected by L-phenylalanine, L-tryptophan, and L-tyrosine in decreasing order and the D-amino acids had little or no effect. The changes in concentration of biopterin, dihydrobiopterin, pterin, sepiapterin, drosopterins, and isoxanthopterin showed a characteristic pattern of increased and/or decreased amounts in response to each of the three L-amino acids. Pterin was regularly increased, and isoxanthopterin decreased. L-Tyrosine caused a 2.1-fold increase in dihydrobiopterin, the largest increase found in this study; L-tryptophan also caused dihydrobiopterin to increase but L-phenylalanine did not. Of 18 eye-color mutants examined, 2 were found to contain high levels of phenylalanine and/or tyrosine, Pu2 and Hnr3. These two mutants, along with prc4 cn/prm2b cn, were shown to be very sensitive to dietary L-phenylalanine, indicating that having low levels of certain pteridines makes them susceptible to toxic effects of these amino acids. Therefore, high levels of aromatic amino acids can perturb the balance among pteridine pools, and low levels of some pteridines in mutants are correlated with the inability to withstand the toxic effects of phenylalanine. From the patterns of change in the pteridines we suggest that tetrahydropterin may also be a cofactor for hydroxylation of phenylalanine, along with tetrahydrobiopterin.
Topics: Amino Acids; Animals; Drosophila melanogaster; Hydroxylation; Mutation; Phenylalanine; Pteridines; Tryptophan; Tyrosine
PubMed: 2496683
DOI: 10.1007/BF00563018 -
FEBS Letters Mar 1993Pteridines are heterocyclic compounds which are synthesized and released by human monocytes/macrophages following stimulation by interferon-gamma. Their concentration in...
Pteridines are heterocyclic compounds which are synthesized and released by human monocytes/macrophages following stimulation by interferon-gamma. Their concentration in various body fluids proved to be indicative for the stimulation of the cellular immune system, and determination of pteridines has become an important diagnostic tool. We show that pteridine derivatives, namely neopterin (N), 7,8-dihydroneopterin (NH2), and 5,6,7,8-tetrahydrobiopterin (BH4) increase intracellular calcium (Cai) in human monocytic cells. Significant increases of Cai are observed at 10 nmol/l NH2, at 100 nmol/l BH4 and at 1 mol/l N, i.e. at concentrations encountered in vivo. At a concentration of 1 mumol/l, Cai is increased (from a control value of 145 +/- 7 nmol/l) to 464 +/- 62 nmol/l (NH2), 340 +/- 41 nmol/l (BH4) and 344 +/- 46 nmol/l (N), respectively. The increase of Cai depends on the presence of extracellular calcium and is likely to be due to activation of a calcium channel. We show that the absence of extracellular calcium or the addition of lanthanum ions to the extracellular fluid fully reverses the pteridine-induced increase of Cai. According to these observations, pteridines may mimic the effects of other inflammatory mediators on monocytic cells and seem to be involved in the crosstalk of immunocompetent cells.
Topics: Biopterins; Calcium; Cell Line; Egtazic Acid; Humans; Lanthanum; Monocytes; Neopterin; Pteridines
PubMed: 8440379
DOI: 10.1016/0014-5793(93)80522-v