All systems ↗Fatty acids reach liver
Lower insulin and counter-regulatory signals increase adipose fatty-acid release; hepatic uptake and beta-oxidation rise during fasting.
CELLULAR ENERGY / 05
The liver exports fat-derived carbon.
Ketone bodies are water-compatible carriers made from hepatic acetyl-CoA when fatty-acid supply is high and carbohydrate/hormonal context favors ketogenesis. Other organs convert them back to acetyl-CoA.
Acetyl-CoA accumulates
Beta-oxidation supplies acetyl-CoA and reducing equivalents while oxaloacetate is also used to support gluconeogenesis.
HMG-CoA pathway builds ketones
Mitochondrial HMG-CoA synthase and lyase form acetoacetate, which interconverts with beta-hydroxybutyrate according to redox state.
Ketones enter blood
Acetoacetate and beta-hydroxybutyrate circulate without lipoprotein packaging; a small fraction of acetoacetate becomes acetone.
Tissues import ketones
Monocarboxylate transporters move ketone bodies into cells and across mitochondrial membranes according to gradients and expression.
Carbon returns to acetyl-CoA
Beta-hydroxybutyrate is oxidized to acetoacetate; SCOT and thiolase reactions generate acetyl-CoA for the TCA cycle.
Liver cannot use its export
Hepatocytes lack meaningful SCOT activity, preventing a futile cycle and directing ketones toward other organs.
Cell type sets the boundary
Brain increasingly uses ketones during prolonged fasting, while red blood cells cannot because they lack mitochondria.