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Cholesterol Metabolism
Objectives
• Review the regulatory mechanisms of cholesterol metabolism
• Discuss various agents affecting cholesterol metabolism
Net Cholesterol Balance in Humans
Adapted from Dietschy JM. Am J Clin Nutr. 1997;65(suppl):1582S.
Synthesized Cholesterol(900 mg/day)
Fecal Sterols(1200 mg/day)
Liver Regulates Concentration of Cholesterol in LDL
Adapted from Dietschy JM. Am J Clin Nutr. 1997;65(suppl):1582S.
(BA Sequestrants, Stanols)
Steps Involved in Cholesterol Absorption
ABCA1ABCA1
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.
Pathways Affecting Cholesterol Balance
(Intake)(Intake)
Liver
HMG CoA ReductaseHMG CoA Reductase
(Bile(BileAcids)Acids)
(Micellar (Micellar Cholesterol)Cholesterol)
(Esterification)(Esterification)(Synthesis)(Synthesis)
(Excretion)(Excretion)
(Uptake)(Uptake)
ABCA1ABCA1
Pathways Affecting Cholesterol Balance
(Sequestrants,(Sequestrants,
Ursodeoxycholate,Ursodeoxycholate,
Stanols)Stanols)
Dietary Dietary
CholesterolCholesterol
BiliaryBiliary
CholesterolCholesterol
LuminalLuminal
CholesterolCholesterol
BileBile
AcidsAcidsMicellarMicellar
CholesterolCholesterol
CholesterolCholesterol
Cholesterol EstersCholesterol Esters
ACATACAT
CMCM
ABCA1ABCA1
ABCG5ABCG5
ABCG8ABCG8CholesterolCholesterol
TransporterTransporter
Intestinal Epithelial CellIntestinal Epithelial Cell
(Intake)(Intake)
(Bile Acids)(Bile Acids)
(Micellar(Micellar
Cholesterol)Cholesterol)
(Uptake)(Uptake)
(Esterification)(Esterification)
(Excretion)(Excretion)
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
