Mature alpha-HDL returns cholesterol to the liver via two pathways. Which statement correctly describes these pathways?

• A. Direct pathway: cholesterol ester uptake by SR-B1; Indirect pathway: CETP exchanges CE for TG, then CE taken up via LDL receptor
• B. Direct pathway: LDL receptor uptake; Indirect pathway: SR-B1 uptake
• C. Direct pathway: ABCA-1 mediated efflux; Indirect pathway: LCAT maturation
• D. Direct pathway: LRP receptor uptake; Indirect: VLDL uptake

Answer: (A)

Mature HDL returns cholesterol to the liver through two routes that together describe reverse cholesterol transport. The direct route is through the liver’s SR-B1 receptor, which binds HDL and allows selective uptake of cholesteryl esters from the HDL particle while the particle itself remains largely intact. The indirect route involves CETP, which exchanges cholesteryl esters in HDL for triglycerides from apoB-containing lipoproteins (like VLDL and LDL). After this exchange, the cholesterol esters are carried by those lipoproteins and are taken up by the liver via LDL receptors. This combination—direct uptake of HDL CE by SR-B1 and indirect transfer of CE via CETP followed by LDL-receptor–mediated uptake—correctly describes the two pathways. The other options mix up the players involved in HDL maturation and uptake (such as ABCA-1 and LCAT) or describe receptors and pathways not central to the mature HDL routes.