Plastids, organelles that evolved from cyanobacteria via endosymbiosis in eukaryotes, provide carbohydrates for the formation of biomass and for mitochondrial energy production to the cell. They generate their own energy in the form of the nucleotide adenosine triphosphate (ATP). However, plastids of non-photosynthetic tissues, or during the dark, depend on external supply of ATP. A dedicated antiporter that exchanges ATP against adenosine diphosphate (ADP) plus inorganic phosphate (Pi) takes over this function in most photosynthetic eukaryotes. Additional forms of such nucleotide transporters (NTTs), with deviating activities, are found in intracellular bacteria, and, surprisingly, also in diatoms, a group of algae that acquired their plastids from other eukaryotes via one (or even several) additional endosymbioses compared to algae with primary plastids and higher plants. In this review, we summarize what is known about the nucleotide synthesis and transport pathways in diatom cells, and discuss the evolutionary implications of the presence of the additional NTTs in diatoms, as well as their applications in biotechnology.

• Klíčová slova
• adenosine triphosphate (ATP), endosymbiosis, evolution, photosynthesis, plastid, synthetic biology, transport,
• MeSH
• biologická evoluce MeSH
• biologický transport MeSH
• biotechnologie MeSH
• membránové transportní proteiny chemie   metabolismus   MeSH
• nukleotidy biosyntéza   metabolismus   MeSH
• rozsivky metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• membránové transportní proteiny MeSH
• nukleotidy MeSH

Cancer cells depend on nucleotides for proliferation. Inhibition of nucleotide metabolism by antimetabolites is a well-established anticancer therapy. However, resistance and toxicity to antimetabolite treatments reduce their effectiveness. Here, we focus on the pyrimidine de novo synthesis pathway, which is crucial for cancer cell proliferation, yet its pharmacological targeting in cancer has been without much clinical success so far. Hence, it is important to understand how cancer cells cope with the insufficiency of this pathway. Here, we describe a procedure to prepare subcutaneous tumor model deficient in de novo pyrimidine synthesis. For examination of metabolic responses to de novo synthesis blockade in tumors, we propose application of MALDI imaging that allows spatially resolved examination of metabolic responses to de novo synthesis blockade in tumors.

• Klíčová slova
• CRISPR/Cas9, Cancer, MALDI, Metabolism, Nucleotides, Pyrimidines,
• MeSH
• lidé MeSH
• nádory * metabolismus   MeSH
• nukleotidy MeSH
• prostorová analýza MeSH
• pyrimidiny MeSH
• sekvence CRISPR * MeSH
• spektrometrie hmotnostní - ionizace laserem za účasti matrice MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• nukleotidy MeSH
• pyrimidiny MeSH

• Klíčová slova
• ADENOSINE TRIPHOSPHATASE *, AVIAN LEUKOSIS VIRUS *, BLOOD CELL COUNT *, CELL DIVISION *, CREATINE KINASE *, DNA, NEOPLASM *, EXPERIMENTAL LAB STUDY *, METABOLISM *, NAD *, NUCLEOTIDES *, NUCLEOTIDYLTRANSFERASES *, POULTRY *, SPECTROPHOTOMETRY *,
• MeSH
• adenosintrifosfatasy * MeSH
• buněčné dělení * MeSH
• DNA nádorová * MeSH
• DNA * MeSH
• drůbež * MeSH
• experimentální leukemie * MeSH
• kreatinkinasa * MeSH
• krevní obraz * MeSH
• metabolismus * MeSH
• NAD * MeSH
• nukleotidy * MeSH
• nukleotidyltransferasy * MeSH
• spektrofotometrie * MeSH
• virus ptačí leukózy * MeSH
• výzkum * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adenosintrifosfatasy * MeSH
• DNA nádorová * MeSH
• DNA * MeSH
• kreatinkinasa * MeSH
• NAD * MeSH
• nukleotidy * MeSH
• nukleotidyltransferasy * MeSH

To facilitate the association studies in complex diseases characterized by hyperhomocysteinemia, we collected structural and frequency data on single-nucleotide polymorphism (SNPs) in 24 genes relating to homocysteine metabolism. Firstly, we scanned approximately 1.2 Mbp of sequence in the NCBI SNP database (dbSNP) build 110 and we detected 1353 putative SNPs with an average in silico genic density of 1:683. Out of 112 putative SNPs in coding regions (cSNPs), we selected a subset of 42 cSNPs and we assessed the applicability of the NCBI dbSNP to the Czech population - a typical representative of European Caucasians - by determining the frequency of the putative cSNPs experimentally by PCR-RFLP or ARMS-PCR in at least 110 control Czech chromosomes. As only 25 of the 42 analyzed cSNPs met the criterion of >/=1% frequency, the positive predictive value of the NCBI data set for our population reached 60%, which is similar to other studies. The correlation of SNP frequency between Czechs and other Caucasians - obtained from NCBI and/or literature - was stronger (r(2)=0.90 for 20 cSNPs) than between Czechs and general NCBI database entries (r(2)=0.73 for 27 cSNPs). Moreover, frequencies of all 20 putative cSNPs, for which data in Caucasians were available, were congruently below or above the 1% frequency criterion both in Czechs and in other Caucasians. In summary, our study shows that the NCBI dbSNP is a useful tool for selecting cSNPs for genetic studies of hyperhomocysteinemia in European populations, although experimental validation of SNPs should be performed, especially if the cSNP entry lacks any frequency data in Caucasians.

• MeSH
• běloši genetika   MeSH
• databáze genetické MeSH
• exprimované sekvenční adresy MeSH
• frekvence genu genetika   MeSH
• genetické markery genetika   MeSH
• genom lidský * MeSH
• homocystein metabolismus   MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• komplementární DNA chemie   MeSH
• lidé MeSH
• veřejný sektor MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Československo MeSH
• Názvy látek
• genetické markery MeSH
• homocystein MeSH
• komplementární DNA MeSH

• Klíčová slova
• CARBON DIOXIDE *, CYANIDES *, ERYTHROCYTES *, EXPERIMENTAL LAB STUDY *, FUMARATES *, HYDRAZINES *, LACTATES *, MALATES *, MANOMETRY *, METABOLISM *, NAD *, PHARMACOLOGY *,
• MeSH
• erytrocyty * MeSH
• farmakologie * MeSH
• fumaráty * MeSH
• hydraziny * MeSH
• kyanidy * MeSH
• laktáty * MeSH
• maláty * MeSH
• manometrie * MeSH
• metabolismus * MeSH
• NAD * MeSH
• oxid uhličitý * MeSH
• výzkum * MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fumaráty * MeSH
• fumaric acid MeSH Prohlížeč
• hydraziny * MeSH
• kyanidy * MeSH
• laktáty * MeSH
• maláty * MeSH
• NAD * MeSH
• oxid uhličitý * MeSH

• Klíčová slova
• ADENINE NUCLEOTIDES *, ADENOSINE TRIPHOSPHATE *, COENZYMES *, EXPERIMENTAL LAB STUDY *, HEXOSEPHOSPHATES *, METABOLISM *, MUSCLES *, PHOSPHORUS ISOTOPES *, RATS *, SCIATIC NERVE *,
• MeSH
• adeninnukleotidy * MeSH
• adenosintrifosfát * MeSH
• denervace svalu * MeSH
• fosfáty * MeSH
• hexosafosfáty * MeSH
• izotopy fosforu * MeSH
• koenzymy * MeSH
• krysa rodu Rattus MeSH
• metabolismus * MeSH
• nervus ischiadicus * MeSH
• svaly * MeSH
• výzkum * MeSH
• Check Tag
• krysa rodu Rattus MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adeninnukleotidy * MeSH
• adenosintrifosfát * MeSH
• fosfáty * MeSH
• hexosafosfáty * MeSH
• izotopy fosforu * MeSH
• koenzymy * MeSH

• Klíčová slova
• ADENINE NUCLEOTIDES *, EXPERIMENTAL LAB STUDY *, INSECTS *, METABOLISM *, MUSCLES *, PHOSPHORUS *,
• MeSH
• adeninnukleotidy * MeSH
• energetický metabolismus * MeSH
• fosfor dietní * MeSH
• fosfor * MeSH
• hmyz * MeSH
• homeostáza * MeSH
• metabolismus * MeSH
• sloučeniny fosforu * MeSH
• svaly * MeSH
• výzkum * MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adeninnukleotidy * MeSH
• fosfor dietní * MeSH
• fosfor * MeSH
• sloučeniny fosforu * MeSH

Purine and pyrimidine nucleotides influence many metabolic pathways and their analogs have been widely used in medicine. A capillary electrophoretic method was developed for measuring intracellular nucleotides. The final BGE consisted of 40 mM citric acid with addition of 0.8 mM CTAB titrated by gamma-aminobutyric acid to pH 4.4. The electrophoretic separations were carried out in an uncoated silica capillary (id/od - 75/375 microm; effective/total length - 90/97 cm). The method allows a complete separation of 21 nucleotides and deoxynucleotides within 15 min with separation efficiencies up to 400,000 theoretical plates per meter. Due to the use of an acidic separation medium, the method offers a high selectivity toward the studied analytes versus possible interferences from matrices. Sample preparation was optimized in order to shorten work-time and prevent analyte degradation. The method was applied for analyzing nucleotides in human erythrocytes and Chinese hamster ovary cells. Diagnostic potential for inherited metabolic disorders of nucleotide metabolism is presented.

• MeSH
• cetrimoniové sloučeniny chemie   MeSH
• cetrimonium MeSH
• CHO buňky MeSH
• Cricetulus MeSH
• elektroforéza kapilární metody   MeSH
• erytrocyty chemie   MeSH
• GABA chemie   MeSH
• koncentrace vodíkových iontů MeSH
• křečci praví MeSH
• kyselina citronová chemie   MeSH
• lidé MeSH
• purinové nukleotidy analýza   MeSH
• pyrimidinové nukleotidy analýza   MeSH
• zvířata MeSH
• Check Tag
• křečci praví MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cetrimoniové sloučeniny MeSH
• cetrimonium MeSH
• GABA MeSH
• kyselina citronová MeSH
• purinové nukleotidy MeSH
• pyrimidinové nukleotidy MeSH

The ATP-binding cassette family transporter MRP2 (multidrug resistance-associated protein 2), encoded by the ABCC2 gene, is involved in the renal excretion of numerous xenobiotics and it is likely that it also transports many endogenous molecules arising from not only normal essential metabolic processes but also from environmental toxins or food intake. We used a targeted gas chromatography-mass spectrometry metabolomics analysis to study whether endogenous organic anions are differentially excreted in urines of healthy volunteers according to their genotype for three functional single nucleotide polymorphisms (SNPs) in ABCC2. This was the case for 35 of the 108 metabolites analyzed. Eight of them are most likely substrates of MRP2 since they are the most contributive to the difference between carriers of a decreasing function allele vs those carrying an increasing function one. Seven out of 8 metabolites are fatty acids (dodecanoic acid; 3-hydroxypropanoic acid) or metabolites of polyphenols (caffeine; resorcinol; caffeic acid; 2-(3,4-dihydroxyphenyl) acetic acid; and 4-hydroxyhippuric acid). Most of them were structurally similar to a series of substances previously shown to interact with MRP2 function in vitro. Interestingly, coproporphyrin isomer I, a prototypical substrate of MRP2, also belonged to our final list although it was not significantly discriminant on its own. This suggests that the simultaneous measurement of a set of endogenous metabolites in urine, rather than that of unique metabolites, has the potential to provide a phenotypic measure of MRP2 function in vivo. This would represent an innovative tool to study the variability of the transport activity of MRP2 under a physiological or pathological condition, especially in pharmacokinetic studies of its substrates.

• Klíčová slova
• ABCC2, Endogenous substrates, Metabolomics, Multidrug resistance-associated protein 2, Single nucleotide polymorphisms,
• MeSH
• alely MeSH
• analýza hlavních komponent MeSH
• biologické markery moč   MeSH
• biologické modely * MeSH
• diskriminační analýza MeSH
• dospělí MeSH
• eliminace ledvinami * MeSH
• exony MeSH
• frekvence genu MeSH
• genetické asociační studie MeSH
• jednonukleotidový polymorfismus * MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• metabolomika metody   MeSH
• mladý dospělý MeSH
• organické látky moč   MeSH
• plynová chromatografie s hmotnostně spektrometrickou detekcí MeSH
• protein spojený s mnohočetnou rezistencí k lékům 2 MeSH
• proteiny spojené s mnohočetnou rezistencí k lékům genetika   metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• validační studie MeSH
• Geografické názvy
• Francie MeSH
• Názvy látek
• ABCC2 protein, human MeSH Prohlížeč
• biologické markery MeSH
• organické látky MeSH
• protein spojený s mnohočetnou rezistencí k lékům 2 MeSH
• proteiny spojené s mnohočetnou rezistencí k lékům MeSH

• Klíčová slova
• ADENINE NUCLEOTIDES *, ASPARTATE AMINOTRANSFERASE *, CARBOHYDRATE METABOLISM *, DOGS *, EXPERIMENTAL LAB STUDY *, GLUTATHIONE *, HEART ARREST *, HEART, MECHANICAL *, HYPOTHERMIA, INDUCED *, METABOLISM *, MYOCARDIUM *,
• MeSH
• adeninnukleotidy * MeSH
• aspartátaminotransferasy * MeSH
• energetický metabolismus * MeSH
• glutathion * MeSH
• hypotermie * MeSH
• metabolismus sacharidů * MeSH
• metabolismus * MeSH
• myokard * MeSH
• psi MeSH
• srdce * MeSH
• srdeční zástava * MeSH
• terapeutická hypotermie * MeSH
• umělé srdce * MeSH
• výzkum * MeSH
• zvířata MeSH
• Check Tag
• psi MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adeninnukleotidy * MeSH
• aspartátaminotransferasy * MeSH
• glutathion * MeSH