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.
PDH & TCA cycle
Pyruvate → acetyl-CoA (PDH, five cofactors: 'Tender Loving Care For Nancy'), then acetyl-CoA + oxaloacetate → citrate and round the cycle: 3 NADH + 1 FADH₂ + 1 GTP + 2 CO₂ per acetyl-CoA (~10 ATP). Regulated at citrate synthase, isocitrate DH (rate-limiting) and α-KG DH.
Click any metabolite on the map for its reactions. Source: FMK-02.1 Glycolysis & TCA; FMK-02.4 Mitochondrial metabolism.
Reactions
| Step | Enzyme | Cofactors | Regulation |
|---|---|---|---|
| Pyruvate → Acetyl-CoA | Pyruvate dehydrogenase complex (PDH) PDH deficiency — neonatal lactic acidosis, neurologic defects; treat with a ketogenic diet (lysine, leucine) so fuel bypasses pyruvate Pyruvate dehydrogenase complex (PDHC) deficiency → |
TPP (thiamine, B₁), Lipoic acid, CoA (pantothenate, B₅), FAD (riboflavin, B₂), NAD⁺ (niacin, B₃) | + Pyruvate (inhibits PDH kinase); Ca²⁺ & insulin (activate PDH phosphatase → dephosphorylated, active E1) − Acetyl-CoA; NADH; ATP (all activate PDH kinase → phosphorylated, inactive E1); Arsenite (binds lipoic acid) |
| Pyruvate → Oxaloacetate | Pyruvate carboxylase | Biotin (B₇), ATP | + Acetyl-CoA |
| Acetyl-CoA → Citrate | Citrate synthase | — | − ATP; NADH; Citrate (product) |
| Oxaloacetate → Citrate | Citrate synthase | — | |
| Citrate → Isocitrate | Aconitase | — | |
| Isocitrate → α-Ketoglutarate | Isocitrate dehydrogenase ★ | NAD⁺ → NADH, CO₂ released | + ADP; Ca²⁺ − ATP; NADH |
| α-Ketoglutarate → Succinyl-CoA | α-Ketoglutarate dehydrogenase complex | TPP (B₁), Lipoic acid, CoA, FAD, NAD⁺ → NADH, CO₂ released | + Ca²⁺ − Succinyl-CoA; NADH; ATP; Arsenite |
| Succinyl-CoA → Succinate | Succinyl-CoA synthetase (succinate thiokinase) | GDP → GTP (substrate-level) | |
| Succinate → Fumarate | Succinate dehydrogenase (Complex II) | FAD → FADH₂ | − Malonate (competitive) |
| Fumarate → Malate | Fumarase | — | |
| Malate → Oxaloacetate | Malate dehydrogenase | NAD⁺ → NADH |
Conditions that live on this map
Beriberi (wet and dry)Korsakoff syndromeMaple syrup urine disease (MSUD)Pyruvate dehydrogenase complex (PDHC) deficiencyThiamine (vitamin B₁) deficiencyWernicke encephalopathy
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
Yield
- Per acetyl-CoA, one turn of the TCA cycle yields — 3 NADH + 1 FADH₂ + 1 GTP + 2 CO₂ (~10 ATP)
- Steps of the TCA cycle that release CO₂ — Isocitrate dehydrogenase and α-ketoglutarate dehydrogenase
- The only TCA enzyme that makes FADH₂ — Succinate dehydrogenase (Complex II)
Cofactor
- Enzymes that need thiamine (TPP) — PDH, α-ketoglutarate dehydrogenase, branched-chain α-keto acid dehydrogenase, transketolase
- Cofactor of pyruvate carboxylase — Biotin (B₇) with ATP; activated by acetyl-CoA
- Mnemonic 'Tender Loving Care For Nancy' stands for — TPP, Lipoic acid, CoA, FAD, NAD⁺ — the PDH / α-KG DH cofactors
Shuttle
- Cytosolic NADH from glycolysis enters mitochondria via — Malate-aspartate shuttle (2.5 ATP each) or glycerol-3-phosphate shuttle (1.5 ATP each)
Enzyme deficiency
- Thiamine deficiency blocks which two TCA-related enzymes? — PDH and α-ketoglutarate dehydrogenase → ↑ pyruvate & lactate, ↓ ATP (Wernicke (confusion, ataxia, ophthalmoplegia), Korsakoff, wet/dry beriberi.)
- Deficiency of Pyruvate dehydrogenase complex (PDH) causes… — PDH deficiency — neonatal lactic acidosis, neurologic defects; treat with a ketogenic diet (lysine, leucine) so fuel bypasses pyruvate (E1 pyruvate decarboxylase (TPP), E2 dihydrolipoyl transacetylase (lipoic acid, CoA), E3 dihydrolipoyl dehydrogenase (FAD, NAD⁺). Thiamine deficiency blocks it → pyruvate → lactate. Give thiamine BEFORE glucose.)
Rate-limiting step
- Rate-limiting enzyme of pdh & tca cycle — Isocitrate dehydrogenase (First oxidative decarboxylation; the rate-limiting step of the cycle.)