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Figure 1 Pharmacodynamics of methotrexate in RA

Published byJosé Miguel Espejo Gil Modified over 6 years ago

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1 Figure 1 Pharmacodynamics of methotrexate in RA
Figure 1 | Pharmacodynamics of methotrexate in RA. Cellular methotrexate uptake is primarily governed by folate transporter 1 (FOLT, also known as RFC1) with limited contribution from folate receptors. Cellular efflux of methotrexate is governed by ATP-binding cassette (ABCC)-family transporters. Within the cell, methotrexate is serially polyglutamated in a reversible reaction governed by folylpolyglutamate synthetase (FPGS) and γ-glutamyl hydrolase (GGH). Polyglutamation of methotrexate (producing methotrexateGlu(1–7)) alters its spectrum of activity, increasing inhibition of dihydrofolate reductase (DHFR), thymidylate synthetase (TYMS), and 5-aminoimidazole- 4-carboxamide ribonucleotide transformylase (ATIC). Polyglutamation also reduces efflux from the cell via ABCC transporters. Brown, P. M. et al. (2016) Mechanism of action of methotrexate in rheumatoid arthritis, and the search for biomarkers Nat. Rev. Rheumatol. doi: /nrrheum

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