During prolonged starvation, which ketone body is produced in the greatest quantity and serves as the primary fuel for the brain?

Explanation

## The Three Ketone Bodies | Ketone Body | Structure | Proportion (%) | Role | Fate | | --- | --- | --- | --- | --- | | **β-hydroxybutyrate** | Reduced form (NADH-derived) | 70–80 | Primary fuel for brain, heart, kidney | Oxidized back to acetoacetate | | **Acetoacetate** | Keto form (first product) | 10–20 | Intermediate; can be reduced or decarboxylated | Reduced to β-hydroxybutyrate or → acetone | | **Acetone** | Volatile ketone | 1–5 | Non-metabolizable byproduct | Exhaled (fruity breath odor) | **Key Point:** β-hydroxybutyrate is the predominant ketone body in blood during prolonged fasting and starvation, accounting for 70–80% of total ketone bodies. It is the preferred fuel for the brain, heart, and kidney cortex. **High-Yield:** The brain normally uses glucose, but during starvation (>3–5 days), it can derive up to 60–70% of its energy from ketone bodies, sparing glucose and reducing protein catabolism. **Clinical Pearl:** The fruity odor of breath in diabetic ketoacidosis (DKA) is due to acetone exhalation. However, acetone itself is not metabolized and is a waste product; the clinically important fuels are β-hydroxybutyrate and acetoacetate. **Mnemonic:** **BAA** = **B**-hydroxybutyrate (biggest), **A**cetoacetate (middle), **A**cetone (smallest). β-hydroxybutyrate is the **B**est fuel for the brain. ## Interconversion in Extrahepatic Tissues ```mermaid flowchart TD A["β-hydroxybutyrate<br/>(from liver blood)"]:::outcome --> B["β-hydroxybutyrate<br/>dehydrogenase<br/>(NAD+ → NADH)"]:::action B --> C["Acetoacetate"]:::outcome C --> D["Succinyl-CoA<br/>transferase<br/>(CoA activation)"]:::action D --> E["Acetoacetyl-CoA"]:::outcome E --> F["Thiolase<br/>(cleavage)"]:::action F --> G["2 × Acetyl-CoA"]:::outcome G --> H["TCA Cycle<br/>ATP generation"]:::action ``` **Note:** Extrahepatic tissues (brain, muscle, kidney) can utilize ketone bodies but cannot synthesize them — they lack HMG-CoA lyase in the appropriate compartment.