During a prolonged fast lasting 72 hours, a 42-year-old woman's blood ketone body concentration rises progressively. Which ketone body is the most common and predominant form in which ketones are transported in the blood during this metabolic state?

Explanation

## Predominant Ketone Body in Blood **Key Point:** β-Hydroxybutyrate is the most abundant ketone body in blood, comprising 70–80% of total circulating ketones during fasting, starvation, and diabetic ketoacidosis. It is the major transport form. ### Ketone Body Synthesis and Interconversion Ketone bodies are produced in the liver through the following sequence: ```mermaid flowchart LR A["Acetyl-CoA<br/>(from β-oxidation)"] --> B["HMG-CoA<br/>(HMG-CoA synthase-2)"] B --> C["Acetoacetate<br/>(primary ketone)"] C -->|"LDH<br/>NADH → NAD⁺"| D["β-Hydroxybutyrate<br/>(70-80% of total)"] C -->|"spontaneous<br/>decarboxylation"| E["Acetone<br/>exhaled via lungs"] D -.->|"LDH<br/>NAD⁺ → NADH"| C ``` ### Why β-Hydroxybutyrate Predominates 1. **Thermodynamic Equilibrium:** The conversion of acetoacetate to β-hydroxybutyrate is catalyzed by lactate dehydrogenase (LDH) and is favored by the high NADH/NAD⁺ ratio in the fed and fasting states. 2. **Hepatic NADH/NAD⁺ Ratio:** During fasting, β-oxidation of fatty acids generates excess NADH, driving the equilibrium toward β-hydroxybutyrate formation. 3. **Stability:** β-Hydroxybutyrate is more stable in blood and tissues than acetoacetate (which spontaneously decarboxylates to acetone). 4. **Efficient Transport:** β-Hydroxybutyrate is readily transported across cell membranes and is the preferred substrate for extrahepatic tissues. **High-Yield:** The ratio of β-hydroxybutyrate to acetoacetate reflects the NADH/NAD⁺ ratio in hepatic mitochondria. In severe metabolic acidosis or shock states, this ratio can exceed 10:1. ### Comparison of the Three Ketone Bodies | Ketone Body | % of Total | Stability | Transport | Metabolism | |-------------|-----------|-----------|-----------|------------| | **β-Hydroxybutyrate** | 70–80% | Stable | Efficient | Oxidized to acetoacetate in tissues | | **Acetoacetate** | 10–20% | Unstable | Moderate | Reduced to β-HB or decarboxylated | | **Acetone** | 5–10% | Volatile | Poor | Exhaled; minimal metabolism | **Clinical Pearl:** The fruity-smelling breath in diabetic ketoacidosis is due to acetone exhalation. However, acetone is a minor ketone body and does not contribute significantly to the metabolic acidosis; the acidosis is caused by acetoacetate and β-hydroxybutyrate. ### Utilization by Extrahepatic Tissues Extrahepatic tissues (brain, heart, kidney, muscle) preferentially oxidize β-hydroxybutyrate because: - It is the most abundant form available - Tissues express 3-ketoacyl-CoA transferase (thiophorase), which converts acetoacetate to acetoacetyl-CoA - β-Hydroxybutyrate is oxidized back to acetoacetate by β-hydroxybutyrate dehydrogenase, then enters the TCA cycle **Mnemonic:** **BHB = Big, Huge, Bulk** (β-Hydroxybutyrate = Biggest, most Huge proportion, Bulk of ketones in blood)