HDL Metabolism



HDL is first synthesized in the liver and small intestine, after which it can uptake cholesterol from peripheral tissues. In order to uptake cholesterol, free cholesterol must first be esterified via LCAT and its cofactor Apo A-I. The resulting cholesteryl ester can then be sequestered in the center of the HDL particle.

Next, there are two main pathways of reverse cholesterol transport. In the direct pathway, the HDL particle returns to the liver, where it drops off its cholesterol load. In the indirect pathway, the cholesterol is transferred to other lipoproteins via CETP. The other lipoproteins can then return the cholesterol to the liver.

Key Points

  • HDL Metabolism
    • Synthesis
      • Takes place in the liver and small intestine
      • Alcohol increases HDL synthesis
    • Acts as a repository for Apo C and Apo E
      • These are needed for chylomicron and VLDL metabolism
    • Participates in reverse cholesterol transport
      • Transports peripheral cholesterol back to the liver
        • Like from atherosclerotic plaques--this is why HDL cholesterol is known as “good” cholesterol
        • Cholesterol is stored in HDL as cholestryl esters
          • These esters are more hydrophobic, which is how HDL sequesters / traps the cholesterol--allowing it to be transported back
          • LCAT converts cholesterol to cholesteryl esters
            • Stands for lecithin-cholesterol acyltransferase
            • Apo A-I is a cofactor for LCAT
      • Direct Pathway
        • HDL directly returns cholesterol to the liver
      • Indirect Pathway
        • HDL donates its cholesterol to other lipoproteins, which then return cholesterol to the liver
          • Cholesterol transfer is mediated by CEPT
            • Stands for cholestryl ester transfer protein