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.
Ethanol metabolism
Three routes converge on acetaldehyde: ADH in the cytosol (NAD⁺ → NADH, the main one), MEOS/CYP2E1 in the smooth ER (NADPH + O₂, inducible, makes ROS), and peroxisomal catalase (minor). ALDH2 then makes acetate → acetyl-CoA. Two NADH per ethanol flood the liver: pyruvate → lactate, OAA → malate, DHAP → glycerol-3-P, β-oxidation inhibited. Result: hypoglycemia (fasting), lactic acidosis, steatosis, ketoacidosis.
Click any metabolite on the map for its reactions. Source: FMK-03.4 Fructose, galactose & ethanol.
Reactions
| Step | Enzyme | Cofactors | Regulation |
|---|---|---|---|
| Ethanol → ADH (cytosol) — main route | Alcohol dehydrogenase (ADH)Methanol poisoning →Ethylene glycol (antifreeze) poisoning → | — | |
| ADH (cytosol) — main route → Acetaldehyde | Ethanol + NAD⁺ → acetaldehyde + NADH + H⁺ | NAD⁺ → NADH | |
| Ethanol → MEOS — CYP2E1 (smooth ER) | MEOS — CYP2E1 (smooth ER) | — | |
| MEOS — CYP2E1 (smooth ER) → Acetaldehyde | CYP2E1: ethanol + NADPH + H⁺ + O₂ → acetaldehyde + NADP⁺ + 2 H₂O | NADPH → NADP⁺, O₂ | |
| Ethanol → Catalase (peroxisome) | Catalase (peroxisomal) | — | |
| Catalase (peroxisome) → Acetaldehyde | Peroxisomal oxidation | H₂O₂ → H₂O | |
| Acetaldehyde → Acetate | Aldehyde dehydrogenase (ALDH2, mitochondrial) ALDH2 polymorphism / disulfiram — acetaldehyde accumulation: flushing, headache, nausea, hypotension after drinking ALDH2 deficiency ('Asian flush', rs671) →Disulfiram (Antabuse) - acetaldehyde reaction → |
NAD⁺ → NADH | − Disulfiram; Metronidazole |
| Acetate → Acetyl-CoA | Acetyl-CoA synthetase (peripheral tissues) | ATP | |
| Acetaldehyde → ↑ NADH / NAD⁺ ratio | Net: 2 NADH per ethanol | — | |
| ↑ NADH / NAD⁺ ratio → Pyruvate → lactate | Lactate dehydrogenase driven forward | NADH → NAD⁺ | |
| ↑ NADH / NAD⁺ ratio → OAA → malate | Malate dehydrogenase driven backwards | NADH → NAD⁺ | |
| ↑ NADH / NAD⁺ ratio → DHAP → glycerol-3-P → TG | Glycerol-3-P dehydrogenase driven forward | NADH → NAD⁺ | |
| ↑ NADH / NAD⁺ ratio → ↓ β-oxidation | 3-Hydroxyacyl-CoA dehydrogenase inhibited | — | |
| Acetyl-CoA → ↑ Ketogenesis | HMG-CoA synthase / lyase (mitochondria) | — |
Conditions that live on this map
Alcohol-induced (alcoholic) hypoglycemiaAlcoholic liver disease (steatosis → hepatitis → fibrosis → cirrhosis)ALDH2 deficiency ('Asian flush', rs671)Disulfiram (Antabuse) - acetaldehyde reactionEthylene glycol (antifreeze) poisoningMethanol poisoning
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
Enzyme deficiency
- Alcoholic hepatitis lab pattern — AST > ALT (≥2:1; alcohol depletes PLP, ALT needs more), ↑GGT, ↑MCV, ↑bilirubin, ↑INR
- Alcoholic ketoacidosis vs DKA — the glucose clue — AKA: glucose normal or low, β-OHB ≫ acetoacetate; DKA: glucose high. AKA needs fluids + glucose + thiamine, no insulin
- Drug that irreversibly inhibits ALDH for aversive therapy — Disulfiram — 'FIRES up acetaldehyde accumulation'
- Deficiency of Aldehyde dehydrogenase (ALDH2, mitochondrial) causes… — ALDH2 polymorphism / disulfiram — acetaldehyde accumulation: flushing, headache, nausea, hypotension after drinking (ALDH2*2 (rs671, ~40% of East Asians) → acetaldehyde accumulates → flushing, nausea, tachycardia (same as disulfiram); ↑ esophageal cancer risk.)
Regulation
- Order of treatment in a hypoglycemic chronic drinker — Thiamine FIRST, then dextrose — glucose without B₁ can precipitate Wernicke encephalopathy
- The three hepatic routes from ethanol to acetaldehyde — ADH (cytosol, NAD⁺, main route), MEOS/CYP2E1 (smooth ER, NADPH + O₂, inducible, ROS), catalase (peroxisome, H₂O₂, minor)
- Which of the three ethanol routes does NOT contribute to the NADH/NAD⁺ shift — MEOS — it spends NADPH. All the hypoglycemia, lactate and steatosis come from ADH + ALDH
Cofactor
- Which pathway uses NADPH instead of NAD⁺ to oxidise ethanol? — MEOS (CYP2E1) — inducible, generates ROS