Cholesterol hepatic metabolism

Cholesterol hepatic metabolism encompasses the molecular and cellular processes by which cholesterol is synthesized, modified, transported, stored, and excreted in the liver. The liver is the major site of cholesterol de novo synthesis (starting from acetyl-CoA), involving rate-limiting enzymes such as HMG-CoA reductase and squalene monooxygenase. Cholesterol is packaged into very low-density lipoproteins (VLDL) for export into circulation, converted to bile acids for excretion, or stored as cholesterol esters. Regulation is mediated by transcription factors like SREBP-2 and controlled via feedback mechanisms responding to cellular cholesterol levels. Excess cholesterol in hepatocytes can trigger pathological processes including fibrosis and carcinogenesis, while hepatic cholesterol metabolism is a major determinant of systemic cholesterol balance and associated cardiovascular risk. Multiple enzymes, transporters (e.g., LDL receptor, NPC1L1, ABCA1, ABCG5/G8), and nuclear receptors (e.g., LXR, FXR) compose the functional network that governs hepatic cholesterol homeostasis.

Other names

Cholesterol metabolismHepatic cholesterol metabolismLiver cholesterol metabolism

Drugs affecting cholesterol hepatic metabolism modulate its various components. This includes inhibition of cholesterol synthesis (e.g., by statins acting on HMG-CoA reductase), inhibition of intestinal cholesterol uptake (e.g., ezetimibe via NPC1L1 inhibition), promotion of reverse cholesterol transport (e.g., by raising HDL levels), and enhancing cholesterol clearance via increased bile acid synthesis.