Plasma Lipoproteins Flashcards
what is the function of lipoproteins?
functions
- to transport ipids to and from tissues
- to keep their lipid components soluble for transport in the plasma
what is the most dense lipoprotein? Least dense?
most dense= HDL
least dense = chylomicrons
there is a high concentration of cholesterol and cholesterol esters in which lipoprotein?
in the LDLs
what is the function of apolipoproteins?
structural components and ligands for cell-surface receptors
- coenzymes for lipid metabolism enzymes
what are the five major classes of apolipoproteins and their subclasses?
apolipoprotein A,B,C,D,E
how are dietary lipids transported throughout the body?
by chylomicrons
describe how Chylomicrons are made and destroyed?
- apolipoprotein synthesis- in rough ER
- lipid synthesis- of TG, cholesterol, phospholipids in smooth ER
- chylomicron assembly in Golgi apparatus -
- maturation - in blood plasma - given Apo C and E from HDLs
- utilization of chylomicron TG by tissues- by activation of lipoprotein lipase (by Apo C/C2)
- clearance of chylomicron remnants (no Apo C present anymore, but Apo E is exposed) - Apo E recognized by liver and remnants are sequentially destroyed
what is the purpose of Apo C and Apo C2? How about Apo E ?
Apo C /C2 activate lipoprotein lipase in tissues and allow for extraction of TGs from the chylomicron
Apo E is recognized by liver receptors
What is the purpose of VLDL, LDL and HDL in the body?
VLDL = transport endogenously synthesised TG
LDL= tranport endogenously synthesized cholesterol
HDL = transport cholesterol from tissues to liver
Describe the synthesis and degradation of VLDLs
- made in liver by process similar to chylomicrons
- secreted into circulation - pick up ApoC/E from HDL
- TG contained in VLDLs is degraded by Lipoprotein lipase
- as TGs are removed, VLDL gets smaller and more dense- eventually becoming LDLs once they lose their ApoC/E
what is the purpose of LDLs?
delivery of cholesterol to the peripheral tissues by receptor mediated endocytosis via LDL receptor
what does the LDL receptor recognise?
it recognizes (Apo B-100) and (Apo E)
what does the LDL receptor NOT recognize?
Apo B-48
how do macrophages become foam cells?
they eat too many oxidised LDLs
what can foam cells lead to?
atherosclerotic plaque
how are HDLs synthesised?
they are formed in the blood by addition of lipids to apolipoprotein Apo A1 which is synthesised by liver and small intestine and develops into nascent HDL
what is the function of HDL cells?
- reservoir of apolipoproteins C/E
- accumulating unesterified cholesterol
- rapid esterification of cholesterol
- reverse cholestrol transport - very important
why does cholesterol need to be transported back to the liver?
for conversion to bile salts
excretion of bile
and use in steroid synthesis
Hypertriglyceridaemia is a disorder of what?
of VLDL and chylomicrons
- lipoprotein lipase deficiency = lack of metabolism of TG
- apoprotein C2 deficiency = no activation of LPL
hypercholesterolaemia is a disorder of what?
of LDLs
- lack of LDL receptor in heterozygous familial hypercholesterolaemia
- apoprotein B100 gene mutation - required for bindin gLDL to receptor
- polygenic hypercholesterolaemia - most high cholesterol cases
Tangier disease is a disorder of what?
of HDLs
it is a mutation of the ABCA1 gene - leads to low plasma HDL cholesterol and accumulatio of cholesterol in tissues
what is familial autosomal dominant HDL deficiecy?
ABCA1 gene mutation - leads to low HDL levels
what is the most common patient group for hyperlipidaemia
polygenic - increased risk of CV disease due to high LDL levels and suppression of HDL by high TG levels