Lect 2- Disorders of Lipoprotein Metabolism Flashcards
lipoprotein definition
transport hydrophobic lipids (TG, chol, fat-soluble vitamins)
2 functions:
1.) absorption of dietary chol, long-chain fatty acids, and fat-soluble vitamins
2.) transport from liver to peripheral tissues and vice versa
What is in the core of lipoproteins?
Cholesterol esters and TGs
Which parts of the lipoprotein are hydrophilic?
Protein, cholesterol, phospholipids (some can be modified and moved inside the core)
HDL
very tiny and very dense
LDL
low density lipoproteins
Little bit larger but less dense than HDL
Bad guys= strong clinical evidence that correlates w/ increased risk of atherosclerosis and other CV diseases
IDL
intermediate density lipoproteins
VLDL
very low density lipoproteins
chylomicrons
largest
Big diff b/w these and all other lipoproteins b/c these are involved in absorption of dietary lipids
Carry all these lipids from gut to other tissues
Which lipoproteins transport TGs?
chylomicrons and VLDLs
Which lipoproteins transport cholesterol and cholesterol esters?
LDLs, HDLs
Apolipoproteins
activate enzymes important in lipoprotein metabolism
ligands for cell surface receptors
ApoB-48
synthesized in ONLY intestine
part of chylomicrons
ApoB-100
synthesized in liver (liver makes VLDL and IDL and LDL originate from VLDL)
on VLDL, IDL, LDL
ApoE
ligand for VLDL receptors
Which apolipoprotein does not transfer b/w lipoproteins?
ApoB
Lipoproteins normally interact w/ each other and exchange substances (lipids and proteins)
ApoC
important in lipoprotein lipase (LPL) rxn
on chylomicrons, VLDL, IDL
lipoprotein lipase
Enzyme to digest TG which are inside the chylomicron (hydrolysis rxn)
Responsible for hydrolysis of TG into glycerol and FA’s which can be used as energy
hepatic lipase
makes IDL into LDL
transport of lipids
LOOK AT SLIDE W/ PICTURE
ApoA-1
on HDL
made in liver or small intestine
LCAT
makes cholesterol into cholesterol esters so they can be moved into the core of HDL
CETP (cholesterol ester transport protein)
Moves esters from HDL to chylomicrons and VLDL
HDL metabolism and reverse chol transport
LOOK AT PICTURE ON SLIDE
amts of chol in chylomicrons
low levels of TC, high levels of TGs
high amts of LDL results in __ amts of TC
high
Which cholesterol is high in pancreatitis?
chylomicrons
Which cholesterol is high in coronary atherosclerosis?
very high levels of LDL!
primary disorders in lipoprotein metabolism
genetic
abnormalities in lipoprotein metabolism is a starting point
Ex. familial hypercholesterolemia
secondary disorders in lipoprotein metabolism
assoc with other comorbidities (obesity, DM, alcohol, etc)
more common than primary
Which genetic hyperlipoproteinemia is most common?
familial hypercholesterolemia
familial hypercholesterolemia
autosomal codominant disorder
increased levels of LDL-C
normal TGs, tendon xanthomas, premature coronary atherosclerosis
higher levels of LDL in homozygotes than heterozygotes
What is mutated in familial hypercholesterolemia?
• Lot of mutations in LDL receptor gene
○ Don’t have proper pickup of LDL → buildup → excess can go to tissues and cause increased risk of atherosclerosis
Homozygotes vs heterozygotes in familial hypercholesterolemia
• Homozygous= chol levels can be 500-1,000
• Heterozygous= chol levels can be 200-400
○ Much lower
• Direct link b/w affected # of alleles affected and function of receptor and severity of disease/ level of chol (homo has disability and death in childhood)
Diagnosis of homozygotes in familial hypercholesterolemia
- Family history
- skin biopsy
- flow cytometry analysis of LDL receptor density
- DNA sequencing
Obesity
increased amts of FFAs are delivered to the liver from adipose tissue (massive amts of VLDLs which can be converted to LDLs)
often assoc w/ insulin resistance
Role of HDL
• HDL is important b/c it is removing cholesterol from the tissues and taking it to the liver to be metabolized
○ Want to reduce the level of LDL and maintain/increase level of HDL in your pts
Type I DM
usually w/o hyperlipidemia if glycemia is under control
Have no prob with lipid metabolism unless they are in ketoacidosis (hypertriglyceridemia due to an increased hepatic FFAs influx from adipose tissue)
Type II DM (high insulin and insulin resistance)
- decreased LPL activity
- increased release of FFAs from adipose tissue
- increased synthesis of FAs in the liver
- increased hepatic prod of VLDLs
Type II DM (lipid abnormalities)
- elevated levels of TGs from VLDL
- increased LDL
- decreased HDL-C
Hypothyroidism
inc LDL-C (due to reduction in activity of LDL receptor)
inc circulating IDL
sometimes mild high TG
ALL pts presenting w/ inc plasma levels of LDL-C, IDL, or TGs should be screened!
nephrotic syndrome
increased hepatic prod and decreased clearance of VLDLs w/ increased LDL prod
Set of clinical features which are assoc with kidney abnormalities
ESRD
end stage renal disease mild hyperTGemia (<300) due to accumulation of VLDLs and remnant lipoproteins in the circulation
renal transplants
pts with these usually have increased lipid levels due to the effect of the drugs required for immunosuppression
hepatitis
increased VLDLs and mild-mod hyperTGemia
severe hepatitis and liver failure
reduced plasma chol and TG
cholestasis
hypercholesterolemia
free chol, coupled w/ phopholipids, is secreted in plasma as constituent of LP-X and can deposit in skin folds and prod xanthomas
alcohol
increased plasma TGs
increased hepatic secretion of VLDLs
regular consumption of HDL-C
screening
all adults >20 should have TC, TG, LDL-C, HDL-C measured after 12 hour overnight fast
diagnosis
determine class/cause of altered lipoproteins
rule out 2’ causes (2’ causes of hyperlipidemia= easier to treat the underlying prob than the lipid problem directly)
fasting glucose= to see if they have DM or not
liver function tests
