Lecture 24: Cholesterol Flashcards
cholesterol (“bile solids”)
-ubiquitous
-30% of human cell membrane
-precursor of BILE ACIDS and STEROID hormones
Where can solid form cholesterol be found?
gallstones
Cholesterol is the precursor of
-bile acids
-steroid horomones
Atherosclerosis
-coronary artery disease and stroke
-caused by cholesterol
Souurces of cholesterol
-diet: 200-300mg/day
-synthesis: 1g/day
major producer of cholesterol
-liver
Chemical properties of cholesterol
-amphipathic
-LOW solubility in water
-high concentration in plasma and bile
Cholesterol transport
-by lipoproteins as a free form (30%) or cholesterol ester (70%)
Cholesterol in bile is solubilized by
-bile acids
-phospholipids
Synthesis of Cholesterol
-from ACETYL CoA in the CYTOSOL
-involves HMG-CoA synthase
-NO HMG-coA lyase activity
Fates of HMG-CoA:
-mevalonate (reductase) (cystols)
-acetoacetate + acetyl-CoA (lyase)(mitochondria)
HMG-CoA reductase
-HMG-CoA to MEVALONATE
-IRREVERSIBLE RATE-limitng step
-uses NADPH reducing cofactor
HMG-CoA supressed by
-cholesterol
-statins
Statins
-COMpetitive INhibtors of HMG-CoA reductase
-can lower plasma cholesterol up to 50%
-atorvastatin (lipitor)
Cholesterol ester
-stored form of cholesterol in the liver
Fates of cholesterol
-cholesterol ester in the liver
-sent out for membranes and steroid synthesis
-converted to bile acids
bile acids
-AMPHIPATHIC
-secreted into bile
-stored in gall bladder
-secreted to small intestine
-EMULSIFYING agents for dietary fat
Bile acids facilitate ___ to emulsify dietary fat
-hydrolysis by pancreatic lypase
-absorption of fat-soluble vitamins
bile acid sequestrants
-cholestryamine and colestipol
-promote excrection of bile acids
Regulation point of cholesterol synthesis
Plasma lipoproteins
-protein/lipid complexes that for aggregates in plasma
-transport lipids from tissue to tissue and participate in lipid metabolism
-distinguished by their density differences
Apolipoproteins
-each class of lipoprotein has characteristic composition
-serve as ligands for cell receptors
Classes of lipoproteins
-HDL
-LDL
-IDL (intermediate)
-VLDL
-chylomicrons
Lipoprotein structure
-INSOLUBLE core
-AMPHIPATHIC shell
Chylomicron role
-transport lipid from INTESTINE to LIVER
-or to becme glycerol and fatty acids (these go to peripheral tissues)
VLDL role in lipid transport
-from liver to IDL
-or gycerol + fatty acids
IDL role in lipid transport
-send to LDL and back to liver
-or glycerol and fatty acids
LDL role in lipid transport
-send back to liver
-send to peripheral tissues
HDL role in lipid transport
-reverse cholesterol transport back to and from liver
Familial hypercholesterolemia
-inherited
-high LDL blood levels
-no feedback inhibtion of cholesterol synthesis
-premature arthreosclerosis and heart attacks
-mutation of LDL receptor or apo B100
Mutations causing hypercholesterolemia
-LDL receptor or apoB100
-little/no LDL receptor production
-delivered to wrong place
-bad binding
-cannot be internalized
