Regarding ketone body metabolism, all of the following statements are true EXCEPT:

Explanation

## Ketone Body Metabolism Overview **Key Point:** Ketone bodies (acetoacetate, beta-hydroxybutyrate, and acetone) are water-soluble alternatives to glucose that fuel extrahepatic tissues during fasting, starvation, and uncontrolled diabetes. However, NOT all ketone bodies are metabolically equivalent. ## Why Each Statement Is Evaluated ### Statement 1: Acetoacetyl-CoA Thiophorase (3-Ketoacyl-CoA Transferase) **Correct.** This enzyme (also called 3-oxoacid CoA-transferase or succinyl-CoA transferase) is present in extrahepatic tissues (brain, muscle, kidney) and catalyzes the transfer of CoA from succinyl-CoA to acetoacetate, forming acetoacetyl-CoA. This is the first step of ketone body utilization outside the liver. [cite:Lehninger Principles of Biochemistry Ch 23] ### Statement 2: HMG-CoA Synthase-2 in Hepatocytes **Correct.** HMG-CoA synthase-2 (the mitochondrial isoform, distinct from the cytosolic HMG-CoA synthase-1 used in cholesterol synthesis) catalyzes the condensation of acetyl-CoA and acetoacetyl-CoA to form HMG-CoA in the mitochondrial matrix. This is the rate-limiting step of ketogenesis and is upregulated during fasting. [cite:KD Tripathi 8e Ch 12] ### Statement 3: Beta-Hydroxybutyrate as Predominant Ketone Body **Correct.** Beta-hydroxybutyrate (D-3-hydroxybutyrate) is the most abundant ketone body in blood during prolonged fasting and ketosis, accounting for ~70% of total ketone bodies. It is readily oxidized by extrahepatic tissues, particularly the brain, which can derive up to 60–70% of its ATP from ketone bodies during prolonged fasting. [cite:Lehninger Principles of Biochemistry Ch 23] ### Statement 4: Acetone as a Metabolically Active Fuel Source **INCORRECT — This is the answer.** Acetone is a ketone body but is NOT metabolically active. It is formed by spontaneous decarboxylation of acetoacetate and is exhaled via the lungs (producing the characteristic "fruity" breath odor in diabetic ketoacidosis). Acetone cannot be re-utilized for energy and is a dead-end product. The two metabolically active ketone bodies are acetoacetate and beta-hydroxybutyrate. [cite:Lehninger Principles of Biochemistry Ch 23] ## High-Yield Summary Table | Ketone Body | Metabolic Role | Fate | | --- | --- | --- | | Acetoacetate | Primary ketone synthesized in liver; utilized by extrahepatic tissues | Reduced to beta-hydroxybutyrate or decarboxylated to acetone | | Beta-hydroxybutyrate | Predominant form in blood; major fuel for brain and muscle | Oxidized back to acetoacetate for entry into TCA cycle | | Acetone | Non-metabolic byproduct | Exhaled via lungs; no energy value | **Mnemonic:** **BAA** = **B**eta-hydroxybutyrate (fuel), **A**cetoacetate (fuel), **A**cetone (absent from metabolism).