acetone

**Biochemistry / Pathophysiology** - Ketone bodies: acetoacetate, β-hydroxybutyrate (BHB), and acetone. - Ketogenesis occurs in hepatic mitochondria when acetyl-CoA from β-oxidation exceeds TCA cycle capacity (low insulin/high glucagon, low oxaloacetate diverted to gluconeogenesis). Pathway: 2 acetyl-CoA → acetoacetyl-CoA → HMG-CoA (HMG-CoA synthase, rate-limiting) → acetoacetate (HMG-CoA lyase). - Acetoacetate → BHB (via BHB dehydrogenase, NADH-dependent; favored when NADH/NAD+ is high, e.g., alcoholic ketoacidosis) or → acetone (spontaneous, non-enzymatic decarboxylation). - Acetone is not used as an energy source by tissues; it is exhaled by the lungs and excreted in urine. This gives the characteristic fruity/sweet breath odor. - Acetoacetate and BHB are acids (they cause the anion-gap metabolic acidosis); acetone is a neutral ketone and does not contribute to acidosis.

**Clinical significance** - Diabetic ketoacidosis (DKA): Kussmaul respirations, fruity breath, abdominal pain, hyperglycemia, anion-gap metabolic acidosis, low bicarbonate, hyperkalemia (total body K+ depleted). Treat with IV fluids, insulin, and potassium repletion (K+ must be checked before insulin). - Other ketosis causes: prolonged fasting/starvation, alcoholic ketoacidosis (high NADH → mostly BHB), low-carbohydrate/ketogenic diets, SGLT2-inhibitor euglycemic DKA, and pregnancy/vomiting. - Testing pearl: Urine nitroprusside tests detect acetoacetate (strongly) and acetone (weakly), but NOT BHB. In DKA, BHB predominates (~3:1 to 10:1 over acetoacetate), so urine ketones may underestimate severity. Early in treatment, BHB converts to acetoacetate, so urine ketones can paradoxically appear worse while the patient improves. Serum BHB is the preferred monitoring test. - Acetone is also a toxic solvent (nail polish remover). Exposure causes CNS depression, mucous membrane irritation, and ketosis without acidosis. Isopropyl alcohol is metabolized by alcohol dehydrogenase to acetone, so isopropanol ingestion causes ketosis (acetone in breath/urine) WITHOUT acidosis or hypoglycemia-based ketoacidosis, with an elevated osmolal gap, CNS depression, and gastritis/hemorrhagic gastritis.

**High-yield associations** - Fruity breath = acetone (DKA). - Ketones in urine without acidosis or high glucose → think isopropyl alcohol ingestion. - Liver cannot use ketone bodies (lacks thiophorase/succinyl-CoA:acetoacetate CoA transferase); RBCs cannot use them (no mitochondria). The brain adapts to using ketone bodies during prolonged starvation. - Fatty acids cannot be converted to glucose, but glycerol can.