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methotrexate folic acid anti-metabolite dicarboxylic inhibitor dermatologic dihydrofolate reductase inhibits cell division enzym auto-immune diseases immunosuppressant rheumatoid arthritis stiffness swelling antifolate l-glutamic joints cancer psoriasis myasthenia gravis alzheimer’s disease immunosuppressive inflammation tumor hypertension molecule amethopterin tetrahydrofolate nucleotide dna rna numerous anti-rheumatic skeletal immune system hydrogen diuretic nitrogen anticancer bone mtx metabolism chemotherapy pregnancy carbon compound conjugate