Cholesterol absorption and metabolism

Cholesterol absorption and metabolism encompasses the dual pathways of exogenous sterol uptake via the intestinal lumen and endogenous synthesis primarily within the liver [PubMed: 28404240]. This complex network is regulated by several key molecular players, notably the NPC1L1 transporter for absorption and HMG-CoA reductase for biosynthesis [StatPearls: NBK542211]. Dysfunctional cholesterol homeostasis is a primary driver of atherosclerotic cardiovascular disease (ASCVD), characterized by the accumulation of low-density lipoprotein (LDL) particles within arterial walls [NCBI: NBK305880]. Therapeutic strategies target various nodes of this system; statins remain the gold standard by inhibiting hepatic synthesis, while ezetimibe selectively inhibits intestinal absorption [PubMed: 25198125]. Newer classes, such as PCSK9 inhibitors and bempedoic acid, provide additional mechanisms for reducing circulating LDL-C by enhancing receptor-mediated clearance or targeting upstream synthesis steps [NIH: PMC4410793]. This entry is classified as incorrect as a single target because it describes a multi-protein biological process rather than a specific molecule.

Other names

Cholesterol homeostasisSterol metabolismEnterohepatic circulation of cholesterolCholesterol transport and biosynthesis

Pharmacological modulation involves the competitive inhibition of HMG-CoA reductase to block hepatic synthesis [StatPearls], the selective inhibition of the Niemann-Pick C1-Like 1 (NPC1L1) protein to prevent intestinal sterol absorption [PubChem], and the inhibition of PCSK9 to prevent LDL receptor degradation, thereby increasing hepatic uptake of circulating LDL-C [PubMed: 25198125].