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.
Ketogenesis & ketone body use
Low insulin / high glucagon → lipolysis → β-oxidation → acetyl-CoA exceeds OAA supply (OAA is being pulled into gluconeogenesis) → HMG-CoA synthase (rate-limiting) → HMG-CoA → HMG-CoA lyase → acetoacetate ⇌ β-hydroxybutyrate (NADH) / acetone (breath). Peripheral tissues reconvert with thiophorase (SCOT). Spares muscle protein in fasting; causes anion-gap acidosis in DKA.
Click any metabolite on the map for its reactions. Source: FMK-05.6 Fatty acid metabolism II.
Reactions
| Step | Enzyme | Cofactors | Regulation |
|---|---|---|---|
| Acetyl-CoA (from β-oxidation) → Acetoacetyl-CoA | Thiolase (2 acetyl-CoA) | — | |
| Acetoacetyl-CoA → HMG-CoA (mitochondrial) | HMG-CoA synthase (mitochondrial) ★ | + acetyl-CoA | + Glucagon / low insulin; High acetyl-CoA, low OAA − Insulin |
| HMG-CoA (mitochondrial) → Acetoacetate | HMG-CoA lyase | releases acetyl-CoA | |
| Acetoacetate → β-Hydroxybutyrate | β-Hydroxybutyrate dehydrogenase | NADH → NAD⁺ | |
| Acetoacetate → Acetone (breath) | Spontaneous decarboxylation | — | |
| β-Hydroxybutyrate → Blood → extrahepatic tissue | Export via MCT transporters | — | |
| Blood → extrahepatic tissue → Acetoacetate (tissue) | β-Hydroxybutyrate dehydrogenase (tissue, reverse) | NAD⁺ → NADH | |
| Acetoacetate (tissue) → Acetoacetyl-CoA (tissue) | Thiophorase (succinyl-CoA:acetoacetate-CoA transferase, SCOT) | Succinyl-CoA → succinate | |
| Acetoacetyl-CoA (tissue) → 2 Acetyl-CoA → TCA | Thiolase | CoA |
Conditions that live on this map
Alcoholic ketoacidosis (AKA)Diabetic ketoacidosis (DKA)
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
Regulation
- Why ketones form: the one-line mechanism — Acetyl-CoA from β-oxidation exceeds oxaloacetate, which gluconeogenesis is consuming — the TCA cycle can't absorb it, so the liver exports it as ketone bodies
- Tissues that can and cannot use ketone bodies — Brain, heart, muscle, kidney can (thiophorase). Liver cannot (no thiophorase) and RBCs cannot (no mitochondria)
- Why the urine dipstick can underestimate ketosis — Nitroprusside detects acetoacetate/acetone but not β-hydroxybutyrate, which dominates when NADH is high (DKA, AKA)
- Ketones spare muscle protein during fasting because — The brain switches to ketones, so less glucose — and less alanine from muscle breakdown — is needed for gluconeogenesis
Enzyme deficiency
- Anion-gap acidosis + hyperglycemia + fruity breath + Kussmaul breathing — Diabetic ketoacidosis — absolute insulin deficiency with unopposed glucagon
- Ketosis with NORMAL/LOW glucose in a malnourished drinker — Alcoholic ketoacidosis
- Hypoglycemia WITHOUT ketones — Fatty acid oxidation defect (MCAD, CPT, carnitine) — the liver can't make acetyl-CoA from fat
Rate-limiting step
- Rate-limiting enzyme of ketogenesis & ketone body use — HMG-CoA synthase (mitochondrial) (Rate-limiting step of ketogenesis. Same intermediate name as cholesterol synthesis but a different compartment (mitochondrion, not cytosol) and a different fate (lyase, not reductase).)