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Electrophoresis Aug 2011Cancer disease is the second leading cause of death in the world. Epidemiology data indicate that early diagnosis of a tumour increases a patient's chance of recovery.... (Review)
Review
Cancer disease is the second leading cause of death in the world. Epidemiology data indicate that early diagnosis of a tumour increases a patient's chance of recovery. Biomarkers are effective instruments which can potentially lead to precancer screening or precancer diagnosis and may provide useful information on the cancer type and the disease's stage of progression. The analysis of new biomarkers for cancer is currently a popular area of study in clinical and cancer research. Pteridines are a class of potential cancer biomarkers. The monitoring levels of pteridines may have prospective value for controlling the course of the malignant process. This review describes the functional employment of pteridines, as biomarkers, in cancer diagnosis. It also contains the description of application of analytical techniques such as high-performance liquid chromatography (HPLC) and capillary electrophoresis (CE) used for pteridine analysis.
Topics: Biomarkers, Tumor; Electrophoresis; Humans; Metabolomics; Neoplasms; Pteridines
PubMed: 21563184
DOI: 10.1002/elps.201000664 -
Clinica Chimica Acta; International... Jan 2011Biomarkers are good potential tools for early cancer diagnosis. Here we have analyzed eight different pteridines in the urine samples of cancer patients and compared...
BACKGROUND
Biomarkers are good potential tools for early cancer diagnosis. Here we have analyzed eight different pteridines in the urine samples of cancer patients and compared them with samples from healthy subjects. Pteridines are important cofactors in the process of cell metabolism, and they have recently become a focal point of cancer screening research because certain pteridine levels have been shown to reflect the presence of cancers.
METHODS
We analyzed 8 pteridines; 6,7-dimethylpterin, 6-biopterin, d-(+)-neopterin, 6-hydroxymethylpterin, pterin, isoxanthopterin, xanthopterin and pterin-6-carboxylic acid using a house-built high-performance capillary electrophoresis with laser-induced fluorescence detection (HPCE-LIF). The levels of pteridines were reported as a ratio of pteridine to creatinine. Statistical hypothesis testing was conducted and P values were calculated to analyze the data.
RESULTS
Among the eight pteridines studied, 6-biopterin, 6-hydroxymethylpterin, pterin, xanthopterin, and isoxanthopterin levels were significantly higher in samples from cancer patients than in those from healthy subjects. Further, xanthopterin and isoxanthopterin levels were compared in breast cancer and lung cancer patients, but no significant difference was observed.
CONCLUSION
Some pteridine levels can be used as biomarkers for noninvasive diagnosis of cancer; however, more data is needed to support this hypothesis.
Topics: Adult; Aged; Biomarkers; Case-Control Studies; Creatinine; Humans; Middle Aged; Neoplasms; Pteridines; Young Adult
PubMed: 20869359
DOI: 10.1016/j.cca.2010.09.015 -
Pigment Cell Research Feb 2002We have identified two simple methods to analyse xanthophore and pterinosome biogenesis in zebrafish. The first uses methylene blue (methylthionium chloride), a redox...
We have identified two simple methods to analyse xanthophore and pterinosome biogenesis in zebrafish. The first uses methylene blue (methylthionium chloride), a redox dye which specifically labels xanthophores and pterinosomes, while the second uses autofluorescence to detect pteridine levels; these methods may be used to detect the number, location and shape of xanthophores and pterinosomes. These assays were applied to two zebrafish mutants--brie and yobo--and revealed that both mutants have pterinosome biogenesis and pteridine synthesis defects. Additionally, using capillary electrophoresis, we provide evidence that sepiapterin is responsible for the yellow colour and blue-light induced fluorescence in zebrafish embryos.
Topics: Animals; Fluorescence; Light; Methylene Blue; Pteridines; Pterins; Ultraviolet Rays; Zebrafish
PubMed: 11837453
DOI: 10.1034/j.1600-0749.2002.00045.x -
Biochemistry Jan 2018Nonribosomal peptide synthetases (NRPSs) produce a wide variety of biologically important small molecules. NRPSs can interface with other enzymes to form hybrid...
Nonribosomal peptide synthetases (NRPSs) produce a wide variety of biologically important small molecules. NRPSs can interface with other enzymes to form hybrid biosynthetic systems that expand the structural and functional diversity of their products. The pepteridines are metabolites encoded by an unprecedented pteridine-NRPS-type hybrid biosynthetic gene cluster in Photorhabdus luminescens, but how the distinct enzymatic systems interface to produce these molecules has not been examined at the biochemical level. By an unknown mechanism, the genetic locus can also affect the regulation of other enzymes involved in autoinducer and secondary metabolite biosynthesis. Here, through in vitro protein biochemical assays, we demonstrate that an atypical NRPS condensation (C) domain present in the pathway condenses acyl units derived from α-keto acids onto a free 5,6,7,8-tetrahydropterin core, producing the tertiary cis-amide-containing pepteridines. Solution studies of the chemically synthesized molecules led to the same amide regiochemistries that were observed in the natural products. The biochemical transformations mediated by the C domain destroy the radical scavenging activity of its redox active tetrahydropterin substrate. Secondary metabolite analyses revealed that the pepteridine locus affects select metabolic pathways associated with quorum sensing, antibiosis, and symbiosis. Taken together, the results suggest that the pathway likely regulates cellular redox and specialized metabolic pathways through engagement with the citric acid cycle.
Topics: Chromatography, Liquid; Genes, Bacterial; Mass Spectrometry; Multigene Family; Peptide Biosynthesis; Peptide Synthases; Photorhabdus; Pteridines
PubMed: 29111689
DOI: 10.1021/acs.biochem.7b00863 -
Human & Experimental Toxicology Jul 2006Occupationally-exposed lead affects the neuromuscular junction and might cause disturbances in the locomotor activity. This study was undertaken to evaluate pteridine... (Comparative Study)
Comparative Study
Occupationally-exposed lead affects the neuromuscular junction and might cause disturbances in the locomotor activity. This study was undertaken to evaluate pteridine metabolism, in which neurotransmitters are synthesized in battery workers. Urinary neopterin, biopterin and creatinine were measured using high performance liquid chromatography. Serum neopterin concentrations were detected by enzyme-linked immunoassay. Blood dihydropteridine reductase (DHPR) activities and deltaaminolevulinic acid (delta-ALA) were measured spectrophotometrically. Blood and urinary lead were detected by atomic absorption spectroscopy. Significantly increased blood and urinary lead levels, urinary neopterin, biopterin and delta-ALA were found in workers, while DHPR activities were indifferent compared to control group. Urinary creatinine decreased. This is the first study to demonstrate that increased activity of the pteridine pathway results in the accumulation of the neurotransmitters that may be responsible for the neurological disorders.
Topics: Adult; Air Pollutants, Occupational; Aminolevulinic Acid; Biomarkers; Biopterins; Creatinine; Dihydropteridine Reductase; Environmental Monitoring; Evaluation Studies as Topic; Humans; Lead; Male; Neopterin; Neuromuscular Junction Diseases; Occupational Exposure; Pteridines
PubMed: 16898163
DOI: 10.1191/0960327106ht634oa -
The Journal of Biological Chemistry May 1997Trypanosomatid protozoans depend upon exogenous sources of pteridines (pterins or folates) for growth. A broad spectrum pteridine reductase (PTR1) was recently...
Trypanosomatid protozoans depend upon exogenous sources of pteridines (pterins or folates) for growth. A broad spectrum pteridine reductase (PTR1) was recently identified in Leishmania major, whose sequence places it in the short chain alcohol dehydrogenase protein family although its enzymatic activities resemble dihydrofolate reductases. The properties of PTR1 suggested a role in essential pteridine salvage as well as in antifolate resistance. 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. Recombinant L. major and Leishmania tarentolae, and native L. major PTR1s, were tetramers of 30-kDa subunits and showed similar catalytic properties with pterins and folates (pH dependence, substrate inhibition with H2pteridines). Unlike PTR1, dihydrofolate reductase-thymidylate synthase showed weak activity with folate and no activity with pterins. Correspondingly, studies of ptr1(-) and dhfr-ts- mutants implicated only PTR1 in the ability of L. major to grow on a wide array of pterins. PTR1 exhibited 2000-fold less sensitivity to inhibition by methotrexate than dihydrofolate reductase-thymidylate synthase, suggesting several mechanisms by which PTR1 may compromise antifolate inhibition in wild-type Leishmania and lines bearing PTR1 amplifications. We incorporate these results into a comprehensive model of pteridine metabolism and discuss its implications in chemotherapy of this important human pathogen.
Topics: Animals; Biopterins; Blotting, Western; Chromatography, Gel; Folic Acid; Folic Acid Antagonists; Humans; Hydrogen-Ion Concentration; Kinetics; Leishmania major; Methotrexate; Models, Chemical; Multienzyme Complexes; NADP; Oxidoreductases; Pteridines; Tetrahydrofolate Dehydrogenase; Thymidylate Synthase
PubMed: 9153248
DOI: 10.1074/jbc.272.21.13883 -
Canadian Journal of Genetics and... Mar 1972
Topics: Animals; Bromine; Chromatography, Paper; Drosophila melanogaster; Extrachromosomal Inheritance; Eye; Fluorescence; Genotype; Kynurenine; Larva; Malpighian Tubules; Methods; Mutation; Pteridines; Riboflavin; Sex Factors; Spectrophotometry; Xanthopterin
PubMed: 4624271
DOI: 10.1139/g72-013 -
Bioorganic & Medicinal Chemistry Letters Jun 2004The preparation of a new 2-carbamoyl pteridine, its activity data against FtsZ from M. tuberculosis (Mtb), and in vitro antibacterial data against Mtb strain H37Ra are...
The preparation of a new 2-carbamoyl pteridine, its activity data against FtsZ from M. tuberculosis (Mtb), and in vitro antibacterial data against Mtb strain H37Ra are presented.
Topics: Antitubercular Agents; Bacterial Proteins; Cytoskeletal Proteins; Mycobacterium tuberculosis; Pteridines
PubMed: 15149666
DOI: 10.1016/j.bmcl.2004.04.012 -
Biochemical and Biophysical Research... Aug 1973
Topics: Aerobiosis; Anaerobiosis; Animals; Carbon Isotopes; Chromatography, Paper; Dialysis; Drug Stability; Hot Temperature; Hydrogen-Ion Concentration; Mixed Function Oxygenases; Orotic Acid; Oxidation-Reduction; Oxygen; Pteridines; Trypanosoma
PubMed: 4731957
DOI: 10.1016/0006-291x(73)90181-2 -
The Journal of Biological Chemistry Dec 1964
Topics: Alcohols; Aldehydes; Chromatography; Ethers; Fatty Acids; Folic Acid; Glycerol; Glyceryl Ethers; Liver; Methotrexate; NAD; NADP; Oxidation-Reduction; Oxidoreductases; Pteridines; Pterins; Rats; Research; Stearic Acids
PubMed: 14247652
DOI: No ID Found