Learn / Metabolism

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

Eicosanoids (COX / LOX) · Membrane phospholipid → cytosol; local hormones acting on GPCRs near where they are made. Enzymes sit beside the arrows, ★ = rate-limiting, ⊕/⊖ = activators/inhibitors (toggle), −ATP +NADH = what the step spends and makes (toggle ⚡), dashed = allosteric signal, shaded bands = compartment. Drag to pan.

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Eicosanoids (COX / LOX)

Free arachidonic acid

Made from Membrane PI — AA at sn-2 by Phospholipase A₂ (PLA₂) ★

Phospholipase A₂ (PLA₂) ★ rate-limiting · irreversible — Eicosanoids (COX / LOX)

Inhibited by: Corticosteroids (induce lipocortin/annexin-1)

"Phospholipase A₂ liberates arachidonic acid from membrane phospholipids (inhibited by corticosteroids)" (s22). Blocking here shuts down BOTH arms — which is why steroids out-perform NSAIDs in asthma and why they carry the broader side-effect profile.

Condition cards:Corticosteroids (phospholipase A2 inhibition) →

Becomes Prostaglandins (PGE₂) — cyclopentane ring via Cyclooxygenase (COX-1 / COX-2)

Cyclooxygenase (COX-1 / COX-2) · irreversible — Eicosanoids (COX / LOX)

Inhibited by: NSAIDs — ibuprofen, naproxen (reversible); Aspirin (irreversible acetylation); Celecoxib (COX-2 selective); Acetaminophen (mainly central)

Deficiency: NSAID-induced GI bleeding — loss of COX-1 prostaglandins that maintain gastric mucus, bicarbonate and mucosal blood flow

COX-1 is constitutive — gastric mucosa, platelets, kidney; COX-2 is induced at sites of inflammation. Blocking COX also removes the protective prostaglandins of the stomach lining, "the mechanistic basis for NSAID-induced GI bleeding" (s22).

Condition cards:NSAID-induced GI bleeding →

Becomes Thromboxane A₂ — oxane ring via Cyclooxygenase (COX-1, platelets)

Cyclooxygenase (COX-1, platelets) — Eicosanoids (COX / LOX)

Inhibited by: Aspirin (irreversible — platelets cannot resynthesise COX)

Thromboxane A₂ "promotes platelet aggregation and vasoconstriction" (s21). Platelets have no nucleus, so aspirin's irreversible acetylation lasts the platelet's ~7–10-day life — the basis of low-dose aspirin for cardiovascular prophylaxis.

Condition cards:Aspirin (irreversible COX suicide inhibition / toxicity) →

Becomes Leukotrienes (LTB₄, LTC₄–E₄) — no ring via 5-Lipoxygenase (5-LOX)

5-Lipoxygenase (5-LOX) — Eicosanoids (COX / LOX)

Inhibited by: Zileuton (5-LOX inhibitor); Montelukast / zafirlukast (receptor antagonists)

"Lipoxygenase (5-LOX) pathway → leukotrienes and lipoxins — unaffected by NSAIDs" (s22). Blocking COX alone can shunt substrate down this arm, which is why NSAIDs are used carefully in asthma.

Becomes Lipoxins — no ring via 5-LOX → lipoxin synthase

5-LOX → lipoxin synthase — Eicosanoids (COX / LOX)

Lipoxins are "no ring, anti-inflammatory, pro-resolving" (s21) — the signal that clears the inflammation the leukotrienes started.