Which ketone body is produced in the largest quantity during prolonged fasting and serves as the primary substrate for extrahepatic tissues?

Explanation

## Ketone Bodies: Production and Utilization **Key Point:** β-Hydroxybutyrate is the predominant ketone body produced during fasting and starvation, accounting for approximately 70% of total ketone bodies. It is the preferred substrate for extrahepatic tissues (brain, muscle, heart) because it is more reduced and energetically favorable. **High-Yield:** The ratio of β-hydroxybutyrate to acetoacetate increases during prolonged fasting and reflects the NAD^+^/NADH ratio in hepatic mitochondria. A high ratio (>3:1) indicates severe ketosis. ## Ketone Body Characteristics | Ketone Body | Production | Utilization | Proportion | Notes | |---|---|---|---|---| | **β-Hydroxybutyrate** | Primary | Extrahepatic tissues | ~70% | Most abundant; reduced form; preferred substrate | | **Acetoacetate** | Intermediate | Extrahepatic tissues | ~20% | Oxidized form; can spontaneously decarboxylate | | **Acetone** | Spontaneous decarboxylation of acetoacetate | Minimal/exhaled | ~10% | Volatile; exhaled in breath ("fruity" odor in DKA) | | **Acetyl-CoA** | Not a ketone body | Substrate for ketogenesis | — | Precursor, not a product | **Clinical Pearl:** In diabetic ketoacidosis, the elevated β-hydroxybutyrate:acetoacetate ratio (often >3:1) is a hallmark finding. Serum β-hydroxybutyrate measurement is more specific for DKA diagnosis than acetoacetate. **Mnemonic:** **"Big B"** — **B**-hydroxybutyrate is the **B**iggest ketone body produced and the **B**est substrate for extrahepatic tissues.