During prolonged starvation (>72 hours), brain glucose consumption decreases significantly because the brain adapts by utilizing which alternative fuel, synthesized in the liver from fatty acid-derived acetyl-CoA?

• A Glycerol derived from adipose triglyceride hydrolysis
• B Lactate recycled via the Cori cycle
• C Ketone bodies (acetoacetate and beta-hydroxybutyrate) ✓
• D Branched-chain amino acids directly oxidized in neurons

Explanation

During prolonged fasting/starvation, adipose lipolysis releases fatty acids that undergo hepatic beta-oxidation, generating excess acetyl-CoA which cannot enter TCA cycle due to low oxaloacetate (OAA is diverted to gluconeogenesis). Excess acetyl-CoA is diverted to ketogenesis: acetoacetate and beta-hydroxybutyrate (ketone bodies) are synthesized in liver mitochondria via HMG-CoA pathway. The brain, which cannot oxidize fatty acids (due to blood-brain barrier impermeability to long-chain fatty acids), adapts to use ketone bodies as fuel, reducing glucose demand by up to 75% during prolonged starvation. This 'glucose-sparing' adaptation conserves muscle protein from gluconeogenic degradation.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

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