Cholesterol Biosynthesis, Transport and Genetics Part 2 Flashcards
how does the body get most of its cholesterol
de novo synthesis
what are the ideal levels of total cholesterol, LDL, HDL and triglycerides for children
total: less than 170
LDL: less than 110
HDL: less than 45
triglycerides: less than 150
what are considered high levels of total cholesterol, LDL, HDL and triglycerides for children
total: over 200
LDL: over 130
HDL: over 45
triglycerides: 200+
what do chylomicrons carry
large particles that carry dietary lipids
what does VLDL carry
endogenous triglyceride and some cholesterol
what does IDL carry
cholesterol esters and triglycerides
what does LDL carry
cholesterol esters
what does HDL carry
cholesterol esters
what are the 3 major normal lipoprotein metabolic pathways
- exogenous
- endogenous
- reverse cholesterol transport
what happens in the exogenous pathway
- dietary cholesterol and fatty acids are absorbed
- triglycerides are formed in the intestinal cell from free fatty acids and glycerol and cholesterol is esterified
- triglycerides and cholesterol combine to form chylomicrons
- chylomicrons enter the circulation and travel to peripheral sites
- in peripheral tissues, free fatty acids are released from the chylomicrons to be used as energy, converted to triglyceride or stored in adipose
- remnants are used in the formation of HDL
what happens in the endogenous pathway
- VLDL is formed in the liver from triglycerides and cholesterol esters
- these can be hydrolyzed by lipoprotein lipase to form IDL or VLDL remnants
- VLDL remnants are cleared from the circulation or incorporated into LDL
- LDL particles contain a core of cholesterol esters and a smaller amount of triglyceride
- LDL is internalized by hepatic and nonhepatic tissues
- in the liver, LDL is converted into bile acids and secreted into the intestines
- in non hepatic tissues, LDL is used in hormone production, cell membrane synthesis or stored
- LDL is taken up by macrophages and other cells which can lead to excess accumulation and the formation of foam cells which are important in plaque formation
what happens in the reverse cholesterol transport pathway
- pre beta HDL particles initiated the efflux of cholesterol and phospholipids from cell membranes via interaction with the ATP transporter A1
- subsequent action of the LCAT esterifies cholesterol in pre beta HDL particles and converts them to mature alpha HDL particles
- mature HDL can deliver cholesterol to the liver by one of the two pathways: directly via the SR-B1 or indirectly exchange of cholesterol esters to chylomicrons, VLDL, or LDL
- the uptake of apoB rich particles occurs via hepatic LDL receptors
- the lypolysis of TG in TG rich HDL by hepatic lipase and endothelial lipase leads to a smaller HDL which re enters the RCT cycle
what are the contributing factors to familial hypercholesterolemia
family history of early cardiac events and high LDL cholesterol
what is the biggest lipoprotein to the smallest
chylomicrons, VLDL, IDL, LDL, HDL
what are the sequential steps in the LDL receptor pathway
- decrease in HMG CoA reductase
- increase in ACAT
- decrease in LDL receptors