Disease relevance of pteridine

• The importance of the ionic interaction due to the formation of the salt bridge between the Asp-27 and the pteridine ring in Escherichia coli dihydrofolate reductase-methotrexate complex has been studied by using the free-energy perturbation method [1].
• Longitudinal sections during leukemias suggested that the biopterin of leukemic cells may be metabolically related to the pteridine moiety of P-AGPM [2].
• It can be concluded that the phage folic acid is a tightly bound baseplate constituent and that the pteridine portion of the folic acid is largely covered by the gene 11 protein [3].
• At this dose the 2 pteridine compounds with diuretic activity exhibited a transient antiarrhythmic effect in abolishing the ouabain-induced ventricular tachycardia while those without diuretic properties failed to suppress the ventricular tachycardia [4].
• GTP cyclohydrolase I (GTPCH) catalyzes the first step in pteridine biosynthesis in Nocardia sp. strain NRRL 5646 [5].

Psychiatry related information on pteridine

• More on aluminum, pteridine, and dialysis dementia [6].

High impact information on pteridine

• Thus, the control of pteridine metabolism has relevance to the mechanism of Leishmania differentiation and the limitation of virulence during evolution [7].
• This conformation has the pteridine rotated approximately 180 degrees away from the orientation of the pteridine ring of methotrexate bound to dihydrofolate reductase [8].
• Folinic acid consists of a mixture of equal parts of two stereoisomers differing in chirality at the C-6 carbon of the pteridine ring [9].
• Descendants of these cell lines and clones contained low but detectable amounts of pteridine pigments (such as 7-hydroxybiopterin, biopterin, xanthopterin, and isoxanthopterin) and numerous cytoplasmic organelles analogous to pterinosomes [10].
• To investigate whether tetrahydrobiopterin functions as an allosteric effector of NOS, we have analyzed the effect of the pteridine on the conformation of neuronal NOS purified from porcine brain by means of circular dichroism, velocity sedimentation, dynamic light scattering and SDS-polyacrylamide gel electrophoresis [11].

Chemical compound and disease context of pteridine

• GTP cyclohydrolase I, an enzyme that catalyzes the first reaction in the pathway for the biosynthesis of the pteridine portion of folic acid, was purified from Escherichia coli by 3,900-fold to apparent homogeneity [12].
• These results indicate that although a guanosine compound serves as the initial precursor for molybdopterin biosynthesis, the early steps of this pathway in E. coli proceed via a pathway unlike that of any known pteridine biosynthetic pathway [13].
• Since mutants lacking MPT converting factor are not auxotrophs for folate or riboflavin, the factor appears to be distinct from known pteridine biosynthetic enzymes in E. coli [14].
• The pteridine neopterin is a marker of immunological activation and has been shown to be a useful marker of graft-versus-host disease (GVHD) in bone marrow transplant patients [15].
• The recombinant version of Trypanosoma cruzi pteridine reductase was expressed in Escherichia coli, purified to homogeneity from the soluble fraction of bacterial extract by metal-chelate affinity chromatography and crystallized in the presence of the cofactor (NADPH) and an inhibitor (methotrexate) at 295 K using sodium acetate as precipitant [16].

Biological context of pteridine

• Structural similarities were identified between this protein and several enzymes that should contain similar nucleotide and pteridine binding sites [17].
• Changes in the length of the polyglutamate side chain and alterations of the pteridine structure such as reduction and/or methylation have a much larger effect on the constant for binding to deoxyhemoglobin tetramers than on that for oxyhemoglobin dimers [18].
• The pteridine binding site of brain nitric oxide synthase. Tetrahydrobiopterin binding kinetics, specificity, and allosteric interaction with the substrate domain [19].
• Coronary endothelial dysfunction in the insulin-resistant state is linked to abnormal pteridine metabolism and vascular oxidative stress [20].
• Furthermore, an inhibitor of a terminal step in pteridine biosynthesis produced an identical phenotype [21].

Anatomical context of pteridine

• In the zebrafish, the peripheral neurons and the pigment cells are derived from the neural crest and share the pteridine pathway, which leads either to the cofactor tetrahydrobiopterin or to xanthophore pigments [22].
• Neopterin is a pteridine produced by human mononuclear phagocytes, usually in response to interferon-gamma (IFN-gamma) stimulation [23].
• The pteridine compounds neopterin and 7,8-dihydroneopterin serve as valuable indicators for the stimulation of the cellular immune system [24].
• Antioxidants partly protected PC12 cells from pteridine-induced apoptosis, suggesting the involvement of reactive oxygen intermediates [25].
• 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 [26].

Associations of pteridine with other chemical compounds

• The folic acid pteridine and phenyl rings interact in a stacking manner which is suggestive of the type of associations these groups could form in a complex of folate, dihydrofolate reductase, and reduced nicotinamide adenine dinucleotide phosphate [8].
• Blood levels of a pteridine-binding alpha 1-acid glycoprotein in cancer patients [2].
• Cells stimulated with interferon-gamma plus LPS, in contrast, showed phenylalanine-independent pteridine synthesis [27].
• To prove this, we have characterized further the properties and relative roles of PTR1 and dihydrofolate reductase-thymidylate synthase in Leishmania pteridine metabolism, using purified enzymes and knockout mutants [28].
• It follows that GTP cyclohydrolase I, the formation of sepiapterin, and the xanthine oxidoreductase family control the pteridine pathway in the zebrafish [22].

Gene context of pteridine

• A direct role for IDO in pteridine synthesis has not been shown, and this parallel induction may reflect coordinate regulation of genes induced by IFN-gamma [29].
• The carbohydrate moiety of the orosomucoid (ORM) molecule shows microheterogeneity [1] and the pteridine-containing variant seems to be tumor-specific [2-4] [30].
• This water molecule, not observed in previously determined DHFR structures, is positioned to complete a proposed route for proton transfer from the side-chain carboxylate of E30 to N5 of the pteridine ring [31].
• The pteridine tetrahydrobiopterin (BH4) is a key feature of NOS, affecting dimerisation and electron transfer, although its full role in catalysis remains to be determined [32].
• The loading regimen was also used to gauge the response of mutant hyperphenylalaninemic mice to exposure to chemical compounds required for normal phenylalanine catabolism (i.e. pteridine cofactors of the phenylalanine hydroxylase reaction) [33].

Analytical, diagnostic and therapeutic context of pteridine

• Examination by light and electron microscopy indicated that these mutant flies have reduced numbers of eye pigment granules, which correlates with decreased levels of both pteridine (red) and ommachrome (brown) pigments [34].
• In embryos mutant for edison, yobo, yocca and brie, differences in pteridine synthesis can be observed under UV light and by thin-layer chromatography [35].
• We incorporate these results into a comprehensive model of pteridine metabolism and discuss its implications in chemotherapy of this important human pathogen [28].
• The effect of folic acid and pteridine analogs on rates of [3H]cAMP secretion, monitored by rapid perfusion, was studied [36].
• Pteridine analysis in urine by capillary electrophoresis using laser-induced fluorescence detection [37].

References