Quantitative metabolomics services for biomarker discovery and validation.
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Dihydrofolate reductase Dihydrofolate reductase Thymidylate synthase Dihydrofolate reductase Folylpolyglutamate synthase, mitochondrial Proton-coupled folate transporter Tetrahydrofolic Acid Transporter Mitochondrial folate transporter/carrier Folate transporter 1 Mitochondrial folate transporter/carrier Gamma-glutamyl hydrolase Monofunctional C1- tetrahydrofolate synthase, mitochondrial Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial Pralatrexate Pralatrexate Tetrahydrofolic acid 5,10-Methylene-THF Folic acid Folic acid Tetrahydrofolic acid Tetrahydrofolic acid Pralatrexate Pralatrexate Dihydrofolic acid NADP NADPH NADPH NADP Tetrahydrofolyl-[Glu](n) H2O L-Glutamic acid ATP Formic acid ADP 10-Formyltetrahydrofolate Pi H+ 5,10-Methenyltetrahydrofolic acid H2O NADH NAD dUMP dTMP NADPH Tetrahydrofolic acid NADP ATP L-Glutamic acid ADP Phosphoric acid THF-L-glutamate Magnesium Purine Metabolism Histidine Metabolism Methionine Metabolism Glycine and Serine Metabolism Glycine and Serine Metabolism Calcium Magnesium Dihydrofolic acid Extracellular Space Cytosol Lysosome Mitochondria Pralatrexate is a folic acid analogue that inhibits enzymes required to produce tetrahydrofolic acid (THF). DNA replication cannot occur due to lack of THF products. 5,10-Methylene-THF, is an intermediate in many amino acid pathways, such as methionine synthesis. It is also used in thymidine synthesis which is a nucleoside needed for DNA replication Cancer Cell Pralatrexate inhibits thymidylate synthase, folylpolyglutamate synthase and dihydrofolate reductase, without these enzymes substrates needed for DNA replication cannot be created and stops cancer cells from proliferation Pralatrexate is administered intravenously and travels to the target within the body
Lysosome Mitochondria DHFR DHFR TYMS DHFR FPGS SLC46A1 Unknown SLC25A32, MFT, MFTC SLC19A1 SLC25A32, MFT, MFTC GGH MTHFD1L MTHFD2 MTHFD2 Pralatrexate Pralatrexate Tetrahydrofolic acid 5,10- Methylene-THF Folic acid Folic acid Tetrahydrofolic acid Tetrahydrofolic acid Pralatrexate Pralatrexate Dihydrofolic acid NADP NADPH NADPH NADP Tetrahydrofolyl- [Glu](n) Water L-Glutamic acid Adenosine triphosphate Formic acid Adenosine diphosphate 10- Formyltetrahydrofolate Phosphate Hydrogen Ion 5,10- Methenyltetrahydrofolic acid Water NADH NAD dUMP dTMP NADPH Tetrahydrofolic acid NADP Adenosine triphosphate L-Glutamic acid Adenosine diphosphate Phosphoric acid THF-L-glutamate Purine Metabolism Histidine Metabolism Methionine Metabolism Glycine and Serine Metabolism Glycine and Serine Metabolism Dihydrofolic acid