•Function •Biosynthesis •Transport in theorganism ...
Cholesterol metabolism
? Function ? Biosynthesis ? Transport in the organism ? Hypercholesterolemia
Cholesterol
- component of all cell membranes - precursor of bile acids
steroid hormones vitamin D
Sources: dietary cholesterol (~ 25% of a daily turnover)
- 0,3g/day
synthesis in tissues (~ 75 %)
- 1 g/day
liver (reproductive tissues -adrenal cortex, ovaries, testes, placenta)
enzymes of biosynthesis present in virtually all tissues
Transport:
as a component of lipoproteins, most as cholesteryl esters
chylomicrons: VLDL: LDL: HDL:
intestine liver
plasma plasma
(extrahepatic tissues)
liver plasma extrahepatic tissues liver
Overview of cholesterol metabolism in liver
Dietary cholesterol
De novo synthesis of cholesterol in liver
Chylomicron remnants
Cholesterol from extrahepatic tissues
HDL
Secretion in HDL and VLDL Free cholesterol secreted in bile
Conversion to Bile acids/salts
Cholesterol excretion
! Steroid ring can not be cleaved in humans
1. cholesterol liver bile acids/salts
bile intestine
feces
cholestanol
2. cholesterol bile
intestine
koprostanol
feces
Cholesterol availability in diets widely varies
balance the rate: cholesterol synthesis
regulatory mechanisms
cholesterol excretion
Imbalance:
elevation of circulating cholesterol excessive cholesterol excretion into bile
coronary artery disease
precipitation in the gallblader
and bile duct
gallstones
Cholesterol biosynthesis
Initial substrate: acetyl-CoA Tissue localization: predominantly liver
mitochondria
acetyl-CoA
farnesyl pyrophosphate
endoplasmic reticulum
citrate
isopentenyl pyrophosphate
translokase for citrate
citrate
oxaloacetate
acetyl-CoA
mevalonate
cytosol
HMG-CoA
squalene lanosterol cholesterol
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