Non-saturable degradation of LDL by monocyte-derived macrophages leads to a reduction in HMG-CoA reductase activity with little synthesis of cholesteryl esters.
In monocyte-derived macrophages from both normal and familial hypercholesterolaemic (FH) subjects, degradation of low density lipoprotein (LDL) through non-saturable pathways produced the same fall in 3-hydroxy-3-methylglutaryl-CoA reductase activity as receptor-mediated degradation of acetylated LDL, yet did not lead to as great an increase in incorporation of [14C]oleate into cholesteryl esters. Studies using FH cells showed that the simultaneous addition of LDL did not reduce oleate incorporation resulting from degradation of acetylated LDL, and that there was a similar relationship for both lipoproteins between the increase in net oleate incorporation and the increase in the cholesteryl ester content of the cells. FH cells maintained in serum-free medium accumulated more free cholesterol than cells in lipoprotein-deficient serum when incubated with LDL but not when incubated with acetylated LDL. The results suggest that the cholesterol released from non-saturable degradation of LDL is more easily removed from the cells by acceptors in the medium than cholesterol released from receptor-mediated uptake of acetylated LDL, and is not readily available for esterification.
D002788:Cholesterol Esters / Q000096:biosynthesis*; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D006938:Hyperlipoproteinemia Type II / Q000097:blood*; D066298:In Vitro Techniques; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000201:enzymology / Q000378:metabolism*; D009000:Monocytes / Q000201:enzymology / Q000378:metabolism*; D011973:Receptors, LDL / Q000502:physiology
D002788:Cholesterol Esters; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D006903:Hydroxymethylglutaryl CoA Reductases