L23 Flashcards
What are the 3 components of the outside of a lipoprotein particle? What is in the core?
Apo-lipoproteins + free cholesterol + phospholipids = outer
Core = TGs + cholesterol esters
What surface molecule is unique LDL? HDL? (remember LDL & HDL are low/high density lipoproteins)
LDL, IDL, VLDL, remnants = apoB (binds LDL receptor)
HDL = apoA1
Equation for LDL
LDL = TC - (TG/5) - HDL
Does the liver secrete VLDL, IDL, or LDL?
VLDL
What happens to VLDL in circulation?
VLDL –> IDL
Releases TGs –> FFAs
- By lipoprotein lipase
FFAs can be taken into tissue for use and E source or into adipocytes for storage
What are IDL
Intermediate density lipoproteins = smaller, cholesterol enriched remnants
What happens to IDL in circulation
- Back to liver - donates cholesterol
2. IDL –> LDL, release more TGs –> FFAs into circulation
What is the fxn of LDL in the blood
Cholesterol transporter to either liver or other tissues
What happens if LDL is oxidized?
= athrogenic form
Can be taken up by marcophages without limit –> foam cell formation –> atherosclerosis
Describe LDL endocytosis
apoB + LDL receptor
In via clatharin coated pits
LDL into lysosome
Receptor recycled to membrane
Fxn of PCSK9 - SEs
LDL receptor degradation - no separation from LDL particle into lysosome
Net increase LDL in circulation b/c no receptors to bind to on tissues
Potential treatment for overactive PCSK9
mAb
Describe familial hypercholesterolemia - 4 most likely causes
High LDL –> premature CHD
- Hetero or homozygous for LDL receptor
- Mutated apoB so can’t bind LDL
- Mutated PCSK9 - excess
- LDL RAP1 mutations - can’t make clatharin pits for endocytosis
Physical exam findings for FH
Xanthomas
- Achilles tendon
- Corneal arcus = young pts
What is phytosterolemia?
Clinically present like FH, but doesn’t have to do with LDL
Increased absorption of non-cholesterol plant sterols
What is familial combined hyperlipidemia (2b)
Overproduce apoB - increased VLDL production
- Increased LDL & TGs
What is type 3 hyperlipidemia? Labs + physical exam findings
"Remnant removal disease" 2 hits - Homozygous for apoE - can't clear LDL correctly - Metabolic condition - T2D, etc High cholesterol, TG, IDL Yellow palm streaks + xanthomas
Steps of TG digestion when eaten in food
- TG uptake - catabolized by gastric & pancreatic lipases
- FFAs –> chylomicrons in lymph –> venous circulation
- Chylomicrons anchors by GPIHBP1 - allows lipoprotein lipase to breakdown TGs –> FFAs
- FFAs stored in fat or muscle
IF you have diabetes, why would you also have high TGs?
Increased adipocyte lipolysis
Excess VLDL secretion
VLDL –> LDL or HDL
Can undergo another TG reduction –> small, denser HDL & LDL
What are the characteristics of smaller, denser HDL and LDL?
sdHDL = less efficient at cholesterol return to liver sdLDL = more athrogenic
Mechanism by which sdLDL is more arthrogenic
Less affinity for LDL receptor - more time in circulation
Easier entry into arterial wall
More susceptible to oxidative damage
Normal blood TG levels
Physical exam findings of high TGs
Xanthomas
Yellow palm streaks
Form layer in plasma overnight
What lifestyle changes can significantly decrease TGs
Weight loss
Low fat diet - high in omega 3s
