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Metabolic pathways

Every FMK pathway as a clickable map. Pick one pathway to hammer it — next step, enzyme, regulator, cofactor, and the facts that get tested (NADPH and who needs it, rate-limiting steps, deficiencies) — or set it to all pathways for a mixed drill. Every answer says which enzyme and which pathway.

Pathway

Purine synthesis & salvage · Cytosol — de novo mainly liver; salvage matters most in brain, marrow and RBCs. Enzymes sit beside the arrows; a ★ marks the rate-limiting step. The map scrolls inside its panel.

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Purine synthesis & salvage

IMP

Made from 5-Phosphoribosylamine by 9 enzymatic steps (4 ATP, 2 × N¹⁰-formyl-THF)

9 enzymatic steps (4 ATP, 2 × N¹⁰-formyl-THF) — Purine synthesis & salvage

Cofactors: N¹⁰-formyl-tetrahydrofolate (two ring-closure steps), Glycine, glutamine, aspartate, CO₂

Inhibited by: Methotrexate (blocks DHFR → no THF regeneration); Sulfonamides (bacterial folate synthesis, PABA analogs)

Folate is the therapeutic target: methotrexate starves rapidly dividing cells (tumour, marrow, gut) of purines. Sulfonamides hit bacterial folate synthesis only — humans eat their folate.

Condition cards:Methotrexate (folate analog) →Sulfonamides (PABA analogs) →

Made from Hypoxanthine (salvage) by HGPRT (hypoxanthine-guanine phosphoribosyltransferase)

HGPRT (hypoxanthine-guanine phosphoribosyltransferase) — Purine synthesis & salvage

Cofactors: PRPP → PPi

Deficiency: Lesch-Nyhan syndrome (X-linked, complete HGPRT loss) — hyperuricemia, gout and stones in a toddler, choreoathetosis/spasticity, cognitive delay, compulsive lip and finger biting; unsalvaged PRPP and low IMP/GMP disinhibit GPAT, so de novo synthesis runs even harder

Salvage: one PRPP instead of 4+ ATP and folate. Brain, marrow and RBCs rely on salvage, which is why losing it is so devastating.

Condition cards:Lesch-Nyhan syndrome →

Becomes AMP via Adenylosuccinate synthetase → adenylosuccinase

Adenylosuccinate synthetase → adenylosuccinase — Purine synthesis & salvage

Cofactors: Aspartate, GTP → GDP

Inhibited by: AMP (feedback on its own branch)

GTP is required to make AMP — cross-regulation balances the pools.

Becomes GMP via IMP dehydrogenase → GMP synthase

IMP dehydrogenase → GMP synthase — Purine synthesis & salvage

Cofactors: NAD⁺, Glutamine, ATP → AMP

Inhibited by: GMP (feedback on its own branch); Mycophenolic acid (IMP dehydrogenase)

ATP is required to make GMP. Mycophenolic acid blocks IMP dehydrogenase — lymphocytes depend on de novo GMP, so it is an immunosuppressant for transplant rejection.

Condition cards:Mycophenolic acid (mycophenolate) →