Objectives • Review the regulatory mechanisms of cholesterol metabolism • Discuss various agents affecting cholesterol metabolism
Net Cholesterol Balance in Humans Synthesized Cholesterol (900 mg/day) Fecal Sterols (1200 mg/day) Adapted fromDietschy JM. Am J Clin Nutr. 1997;65(suppl):1582S.
(BA Sequestrants, Stanols) Liver Regulates Concentration of Cholesterol in LDL Adapted fromDietschy JM. Am J Clin Nutr. 1997;65(suppl):1582S.
ABCA1 ABCA1 Steps Involved in Cholesterol Absorption
Steps of Cholesterol Absorption • Emulsification • Transfer from bile acid micelle to brush border • Transport to endoplasmic reticulum • Esterification (ACAT) • Incorporation into chylomicrons • Secretion from basolateral surface • Movement into lymph Hernandez M, et al. Biochim Biophys Acta. 2000;1486:232-242.
ABCA1 ABCA1 Pathways Affecting Cholesterol Balance Liver (Excretion) (Intake) HMG CoA Reductase (Esterification) (Synthesis) (BileAcids) (Micellar Cholesterol) (Uptake)
Pathways Affecting Cholesterol Balance Dietary Cholesterol BiliaryCholesterol Intestinal Epithelial Cell (Intake) CM (Excretion) Cholesterol Esters LuminalCholesterol ACAT ABCA1ABCG5 ABCG8 (Esterification) BileAcids (Bile Acids) (Sequestrants,Ursodeoxycholate,Stanols) MicellarCholesterol CholesterolTransporter (MicellarCholesterol) Cholesterol (Uptake)
Conclusions • Cholesterol metabolism depends on the delicate interplay of multiple pathways • These pathways maintain a net cholesterol balance between cholesterol synthesis and absorption on one side and cholesterol excretion on the other