Learn / FMK
Every FMK condition
299 diseases, deficiencies, toxicities and drug mechanisms harvested from every FMK deck — the ones sprinkled through a single bullet as much as the ones with their own slide. Pick what you're given and what you have to name, or let it cycle; distractors come from the same category so you have to discriminate (hypoketotic vs. ketotic hypoglycemia, which GSD, which urea-cycle enzyme…). Every answer shows the whole card with the lecture and slide.
Toxin/Drug · FMK 08.1
Methotrexate (folate analog) Acquired / not inherited
Defect / target: Inhibits dihydrofolate reductase (DHFR)
Mechanism: Blocks regeneration of tetrahydrofolate, starving cells of N10-formyl-THF needed for two ring-closure steps of purine synthesis and of the reduced folate cofactor thymidylate synthase needs to make dTMP, so rapidly dividing cells (tumor, marrow, gut epithelium) cannot synthesize DNA.
↑ Accumulates: Dihydrofolate· ↓ Deficient: Tetrahydrofolate, purine nucleotides, dTMP
Presentation: Toxicity in rapidly dividing tissues: myelosuppression, mucositis/GI epithelial injury
Treatment: Leucovorin (folinic acid) rescue
5-FU + methotrexate are combined because they hit the same reaction (thymidylate synthase) from two angles — the enzyme and its cofactor supply
Learn the mechanism: Purine synthesis & salvage →
FMK 08.1 Nucleic Acid Metabolism · slide 9, 24, 29