cholesterol Flashcards
what are the four major classes of lipoprotein particles?
chylomicrons -
VLDL
LDL
HDL
What are the lipid components of lipoproteins?
triglycerols
cholesterol esters
phospholipids
what are the protein components of lipoproteins?
apolipoproteins A-E
activates lipid processing enzymes in blood.
what are the “bad” lipoprotein particles?
chylomicrons
VLDL
IDL
LDL
what are the “good” lipoprotein particles?
HDL
HDL in high levels reduce cardiovascular disease because it extracts cholesterol and cholesterol esthers from cell membranes, vasculature, and atherosclerotic plaques and return them to the liver
why are LDL bad?
increasese cardiovascular disease and stroke
promotes fatty deposits in arteries which reduces or blocks blood flow and oxygen delivery
what is hyperlipidemia?
elevated plasma cholesterol/triglycerides
Describe chylomicrons metabolism
- Made in the intestine and contain apo B48
- chylomicrons are released into lymph
- Chylomicrons acquire apo-CII and apo-E from HDL in plasma
- lipoprotein lipase on surface on non hepatic tissues hydrolize triglycerides
- chylomicron remnants of depleted of glycerol and FFA transfer apo C-II back to HDL
- Remnants w/apoEand apoB48, bind to the apo E receptor on liver cells, resulting in the uptake of remnants
what binds lipoprotein particles?
cell surface receptors
what happens when intracellular cholesterol increases?
expression of cholesterol synthesis gene is blocked
HMG CoA reductase is down regulated
what are the LDL receptor mutations and what do they all lead to?
Class 1 - no receptor synthesized
Class 2 - receptors synthesized but remains in ER or Golgi
Class 3 - receptors lack normal LDL binding
Class 4 - receptors are not clustered in coated pits and endocytosed
They all lead to high blood cholesterol levels
how is extra cholesterol stored ?
stored as cholesterol esters in lipid droplets in the cytosol
what is pcsk9?
a new drug target for ldl cholesterol reduction that binds the ldl receptor and stimulates ldl receptor endocytosis
non functional ldl receptors
makes ldl stay longer in blood stream which increases blockage in the arteries as the plaque hardens and narrows the arteries
Does PCSK9 increase or decrease the levels of LDL receptor at the plasma membrane?
PCSK9 reduces the level of cell surface LDL receptors, thus decreasing the rate of LDL removal and elevating plasma LDL.
Do anti-PCSK9 antibodies increase or decrease the levels of LDL receptor at the plasma membrane? Why?
increases levels of ldl receptors because it allows the ldl receptors to remain and bind to ldl for degradation
Does PCSK9 block the binding of LDL to the LDL receptor?
? idk becaus does not bind where the ldl binds but it makes it get endocytosed so technically the receptor is still open to bind to the ldl
When cholesterol levels are low, where is SCAP-SREBP?
SCAP AND SCREBP move to th golgi and then SREBP is cleaved. cleaved SREBP moves to nucleus to activate genes for cholesterol synthesis.
When intracellular cholesterol levels are low, is HMG CoA reductase phosphorylated or unphosphorylated?
unphosphorlyated because it activates HMGR (HMGR CoA reductase) which increases formation of cholesterol needed in a low level environment
When is HMG CoA reductase likely to be degraded?
when cholesterol is high. HMGR gets misfolded and degraded by 26S proteasome
What organ STORES bile acids and bile salts?
gallbladder
What is the rate limiting step in bile acid synthesis?
cholesterol) 7-a-hydroxylase
what does Apo B100 do?
helps bind lipoprotiens to LDL receptor
what does Apo CII do ?
works on lipoprotein lipase to cut fats
