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Dihydrofolate reductase Dihydrofolate reductase Thymidylate synthase Proton-coupled folate transporter Tetrahydrofolic Acid Transporter Mitochondrial folate transporter/carrier Folate transporter 1 Folate transporter 1 Gamma-glutamyl hydrolase Monofunctional C1- tetrahydrofolate synthase, mitochondrial Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial Pemetrexed Pemetrexed Tetrahydrofolic acid 5,10-Methylene-THF Folic acid Folic acid Tetrahydrofolic acid Tetrahydrofolic acid Pemetrexed Pemetrexed 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 Magnesium Purine Metabolism Histidine Metabolism Methionine Metabolism Glycine and Serine Metabolism Glycine and Serine Metabolism Magnesium Dihydrofolic acid Extracellular Space Cytosol Lysosome Mitochondria Pemetrexed 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 Pemetrexed also inhibits thymidylate synthase which stops thymidine and purine synthesis. Without thymidine and purines DNA replication cannot occur, halting the cancer cells from proliferating. Pemetrexed is administered intravenously and travels to its targets within the body
Lysosome Mitochondria DHFR DHFR TYMS SLC46A1 Unknown SLC25A32, MFT, MFTC SLC19A1 SLC19A1 GGH MTHFD1L MTHFD2 MTHFD2 Pemetrexed Pemetrexed Tetrahydrofolic acid 5,10- Methylene-THF Folic acid Folic acid Tetrahydrofolic acid Tetrahydrofolic acid Pemetrexed Pemetrexed 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 Purine Metabolism Histidine Metabolism Methionine Metabolism Glycine and Serine Metabolism Glycine and Serine Metabolism Dihydrofolic acid
DHFR DHFR TYMS SLC46A1 SLC25A32, MFT, MFTC SLC19A1 SLC19A1 GGH MTHFD1L MTHFD2 MTHFD2 Pemetre Pemetre THFA 5XM-THF Folate Folate THFA THFA Pemetre Pemetre FAH2 NADP NADPH NADPH NADP ThGluN H2O Glu ATP Formate ADP 10-FTHF Pi H+ CH-THF H2O NADH NAD dUMP dTMP Mg2+ PW000052 PW000043 PW000056 PW000157 PW000157 Mg2+ FAH2 Extracellular Space Cytosol Lysosome Mitochondria Pemetrexed 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 Pemetrexed also inhibits thymidylate synthase which stops thymidine and purine synthesis. Without thymidine and purines DNA replication cannot occur, halting the cancer cells from proliferating. Pemetrexed is administered intravenously and travels to its targets within the body
Lysosome Mitochondria DHFR DHFR TYMS SLC46A1 SLC25A32, MFT, MFTC SLC19A1 SLC19A1 GGH MTHFD1L MTHFD2 MTHFD2 Pemetre Pemetre THFA 5XM-THF Folate Folate THFA THFA Pemetre Pemetre FAH2 NADP NADPH NADPH NADP ThGluN H2O Glu ATP Formate ADP 10-FTHF Pi H+ CH-THF H2O NADH NAD dUMP dTMP PW000052 PW000043 PW000056 PW000157 PW000157 FAH2