Uncoupling protein 1 (UCP1, thermogenin) in brown adipose tissue dissipates the proton gradient across the inner mitochondrial membrane as heat rather than ATP synthesis. Which metabolite directly activates UCP1 during cold exposure, and which molecule inhibits it?

• A Activated by ADP; inhibited by ATP via the purinergic receptor
• B Activated by norepinephrine directly binding UCP1; inhibited by insulin
• C Activated by NADH; inhibited by cytochrome c released from the inner membrane
• D Activated by free fatty acids (especially long-chain fatty acids); inhibited by purine nucleotides (ATP, GTP, GDP) ✓

Explanation

UCP1 is activated by free fatty acids, which are released in brown adipose tissue during sympathetic stimulation via norepinephrine → beta-3 adrenergic receptor → cAMP → PKA → lipase activation. The free fatty acids directly interact with UCP1 to enable proton conductance across the inner mitochondrial membrane, generating heat. UCP1 is tonically inhibited by purine nucleotides (GDP, GTP, ADP, ATP), which bind to the cytosolic face. Cold exposure increases sympathetic drive and fatty acid release, overcoming nucleotide inhibition and activating thermogenesis.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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