hyperlipidemia Flashcards
how are non-polar lipids transported in the blood
lipoproteins
what are non-polar lipids
cholesterol esters
triglycerides
describe the lipoprotein core
hydrophobic
contains esterified cholesterol and triglycerides
describe the lipoprotein coat
hydrophilic
contains apoproteins
what apoproteins are contained in HDL
apoA1 and apoA2
what apoproteins are contained in LDL
apoB-100
what apoproteins are contained in VLDL
apoB-100
what apoproteins are contained in chylomircons
apoB-48
what are the major lipoproteins (4)
HDL, LDL, VLDL, chylomicrons
where are chylomicrons formed
intestinal cells
what do chylomicrons transport
dietary triglycerides
what is involved in the exogenous pathway of cholesterol
chylomircons
where are VLDL formed
liver cells
what do VLDL transport
triglycerides synthesised in the liver
what is involved in the endogenous pathway of cholesterol
VLDL
what do apoB lipoproteins do
deliver triglycerides to:
- muscle for ATP biogenesis
- adipocytes for storage
summarise the life cycle of apoB lipoproteins
assembly
intravascular metabolism
receptor mediated clearance
describe the assembly of chylomircons
monoglycerides and free fatty acids from dietary fat enter enterocyte via diffusion and undergo synthesis to form triglycerides
cholesterol from dietary fat and bile enters enterocyte via NPC1L1 where it undergoes esterification to become a cholesterol ester
apoB48 is then added via MTP in the ER a second apoA1
exists via exocytosis
describe the assembly of VLDL
assembled in liver hepatocytes from free fatty acids from adipose tissue and de novo synthesis
MTP adds apoB100 and the VLDL joins with triglyceride droplets
describe activation of VLDL and chylomircons
activated by the transfer of apoCII from HDL particles
describe intravascular metabolism of apo proteins
apoCII facilitates binding of VLDL and chylomicrons to lipoprotein lipase (LPL)
LPL hydrolyses core triglycerodes to free fatty acids and glycerol which enters tissues. the remaining depleted particles are called remnants
describe clearance of apoB lipoproteins
VLDL and chylomircons dissociate from LPL
apoCII is transferred to
HDL is exchange for apoE which is a high affinity ligand for receptor mediated clearance
cells return to liver and are further metabolised by hepatic lipase
all apoB48 and 50% of apoB100 are cleared by receptor-mediated endocytosis into hepatocytes
the remaining apoB100 lose triglycerides through hepatic lipase becoming smaller and lose apoE to become solely apoB100 via intermediate density lipoproteins (IDL)
what is primary dyslipidemia
occurs via a combination of diet and genetic factors
what is secondary dyslipidemia
consequence of other diseases (e.g. type 2 diabetes, alcoholism, liver disease etc)
what is the mechanism of statins
competitive inhibitor of HMG-CoA reductase
what are the main lipid lowering drugs (4)
statins
fibrates
bile binding resins
ezetimibe
examples of statins
simvastatin
atorvastatin
examples of vibrates
bezafibrate
gemfibrozil
what is the mechanism of vibrates
agonist of PPAR-alpha
examples of bile acid binding resins
colestyramine
colestipol
colsevelam
what is the mechanism of bile acid binding resins
cause excretion of bile salts resulting in more cholesterol to be converted to bile salts
what is the mechanism of ezetimibe
inhibits NPC1L1
what is the key role of HD, what is known as
remove excess cholesterol from cells by transporting it in plasma to the liver
reverse cholesterol transport
where is HDL formed
liver
treatment of raised LDL
statin +/- ezetimibe
treatment of raised LDL and VLDL
fibrate OR statin
treatment of raised VLDL
fibrate
treatment of raised VLDL and chylomicrons
(fibrate OR fish oil) + statin
