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.
Electron transport & OXPHOS
NADH → Complex I → CoQ → Complex III → cytochrome c → Complex IV → O₂. FADH₂ enters at Complex II (no protons pumped). Complexes I, III, IV pump H⁺ into the intermembrane space; ATP synthase (Complex V) lets it back in. ~2.5 ATP per NADH, ~1.5 per FADH₂.
Click any metabolite on the map for its reactions. Source: FMK-02.4 Mitochondrial metabolism & energy disorders.
Reactions
| Step | Enzyme | Cofactors | Regulation |
|---|---|---|---|
| NADH → Complex I (NADH DH) | NADH dehydrogenase (FMN, Fe-S) | — | − Rotenone; Amobarbital; MPTP (→ Parkinsonism); Metformin (mild) |
| FADH₂ (succinate) → Complex II (succinate DH) | Succinate dehydrogenase | — | − Malonate |
| Complex I (NADH DH) → Coenzyme Q (ubiquinone) | Electron transfer to ubiquinone | — | |
| Complex II (succinate DH) → Coenzyme Q (ubiquinone) | Electron transfer to ubiquinone | — | |
| Coenzyme Q (ubiquinone) → Complex III (cyt bc₁) | Q-cycle | — | − Antimycin A |
| Complex III (cyt bc₁) → Cytochrome c | Cytochrome c reduction | — | |
| Cytochrome c → Complex IV (cyt c oxidase) | Cytochrome c oxidase (heme a, a₃, Cu) | — | − Cyanide (binds Fe³⁺); Carbon monoxide (binds Fe²⁺); Hydrogen sulfide |
| Complex IV (cyt c oxidase) → O₂ → H₂O | 4 e⁻ + O₂ + 4 H⁺ → 2 H₂O | — | |
| Complex IV (cyt c oxidase) → H⁺ gradient (IMS) | Proton pumping (I, III, IV) | — | |
| H⁺ gradient (IMS) → ATP synthase (Complex V) | H⁺ flow through F₀ | — | − Oligomycin (blocks F₀ channel → gradient can't dissipate → ETC slows) |
| ATP synthase (Complex V) → ATP | Rotational catalysis on F₁ | ADP + Pi → ATP |
Conditions that live on this map
2,4-Dinitrophenol (DNP) toxicityAntimycin A (Complex III inhibition)Aspirin (salicylate) overdoseCarbon monoxide (CO) poisoningComplex I inhibition (rotenone, amobarbital)Cyanide poisoningHydrogen sulfide (H₂S) poisoningIschemia-reperfusion injuryLactic acidosis (Type A and Type B)Leber hereditary optic neuropathy (LHON)Malonate (Complex II inhibition)MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis, Stroke-like episodes)MERRF (Myoclonic Epilepsy with Ragged Red Fibers)Metformin-associated lactic acidosisMPTP-induced ParkinsonismNRTI mitochondrial toxicity (zidovudine, stavudine)Oligomycin (ATP synthase inhibition)Primary mitochondrial disease / mitochondrial myopathy (general pattern)Valproate (VPA) hepatotoxicity / mitochondrial toxicity
Blue pills sit on one specific arrow; grey ones are whole-pathway problems. Each opens the full condition card, which links back here with the arrow lit.
Facts worth knowing
Inhibitor
- Complex I inhibitors — Rotenone, amobarbital (and MPTP, metformin)
- Complex II inhibitor — Malonate
- Complex III inhibitor — Antimycin A
- Complex IV inhibitors — Cyanide, carbon monoxide, hydrogen sulfide
- ATP synthase (Complex V) inhibitor — Oligomycin
- Physiologic uncoupler of brown adipose tissue — UCP1 (thermogenin) — non-shivering thermogenesis in newborns, triggered by cold/norepinephrine via β₃
- Toxic uncouplers — 2,4-Dinitrophenol (DNP) and high-dose salicylates — hyperthermia, ↑O₂ consumption, ↓ATP
Yield
- ATP per NADH vs FADH₂ — ~2.5 per NADH, ~1.5 per FADH₂
- Complexes that pump protons — I (4 H⁺), III (4 H⁺), IV (2 H⁺) — Complex II pumps none
Enzyme deficiency
- Mitochondrial disease with stroke-like episodes and lactic acidosis (m.3243A>G, tRNA-Leu) — MELAS
- Myoclonic epilepsy with ragged-red fibres on Gomori trichrome (m.8344A>G, tRNA-Lys) — MERRF
- Painless subacute bilateral vision loss in young men from Complex I subunit mutations (ND1/ND4/ND6) — Leber hereditary optic neuropathy (LHON)
- Drug that depletes mtDNA by inhibiting polymerase γ (myopathy, lactic acidosis, fatty liver) — NRTIs (zidovudine, stavudine)
- Antiepileptic that impairs β-oxidation and the urea cycle (hyperammonemia, Reye-like hepatotoxicity) — Valproate
Inheritance
- Inheritance of primary mtDNA disease — Maternal — all children of an affected mother; affected males don't transmit; heteroplasmy sets severity (threshold ~70–80%)
- Reperfusion injury is driven by — A burst of ROS (superoxide, hydroxyl radical) as electron flow resumes; defended by SOD, catalase, glutathione peroxidase