Flashcards in Cholesterol and Lipoprotein Metabolism Deck (49):
Where is ApoB found?
VLDL, IDL (chylomicron remnants), LDL
-All considered atherogenic
Where is ApoA-1 and 2 found?
What is ApoE and where is it found?
Expressed on chylomicron remnant, IDL, HDL. Binds to LDLR for uptake into liver
What is ApoC-II and where is it found?
Found on chylomicrons and VLDL. Required cofactor for LPL (needed to activate it)
What is LPL?
Hydrolyzes TGs and frees fatty acids to be taken up by the tissue as fuel. FAs in chylomicron are depleted and eventually you get a chylomicron remnant. In other words, LPL is req for the breakdown of chylomicrons
Chylomicron vs VLDL
Chylomicron is from the gut (i.e. food source) VLDL is from the liver (i.e. fatty acids in body were broken down, went to liver, packaged in VLDL and transported into systemic circulation). VLDL then drops off FAs at key tissues. Eventually they become IDL (remnants)
VLDL remnants that either allow their ApoE to bind to LDLR and can be taken up to liver for breakdown or that lose their ApoE via conversion to LDLs by hepatic lipase.
LDL is IDL without TG or ApoE. It does, however, still have ApoB-100, allowing it to interact with the LDLR receptor. However, since they don't have ApoE also, they are less likely to interact than IDL or other particles
Where is ApoB-100 expressed?
VLDL, IDL, LDL
What lipoprotein is affected in familial chylomicronemia syndrome (FCS)?
What is the etiology of FCS?
Mutation in LPL doesn't allow it to hydrolyze TGs (i.e. break down chylomicrons in the blood) OR mutations in ApoC-2 doesn't allow LPL to activate
What is your TG level in FCS?
What are the physical exam findings in FCS?
Eruptive xanthomas (specific to hyperchylomicronemia)
Clinical consequences of FCS
What lipoprotein is affected with familial hypercholesterolemia (FH)?
What is the etiology of FH?
LDL receptor mutation so that LDL, IDL and CM cannot be taken up by liver
What is your TG level in FH?
Physical exam findings with FH?
Heterozygous: tendon xanthoma (specific), corneal arcus and xanthelasma (common but not specific)
Homozygous: Cutaneous xanthomas
Clinical consequences of FH
-Homozygotes have early onset heart disease
What lipoprotein is affected with familial combined hyperlipidemia (FCHL)?
VLDL and LDL
What is the etiology of FCHL?
Unknown but there is an overproduction of VLDL by the liver with unknown cause (i.e. no insulin resistance etc)
What are the physical exam findings with FCHL?
What is the clinical consequences of FCHL?
What lipoprotein is affected with familial Dysbetalipoproteinemia (FD)
Remnants (IDL and chylomicron)
Etiology of FD?
mutations in ApoE-II so remnants can't bind LDLR
TG level in FD?
Physical findings in FD?
Eruptive palmar tubero xanthomas
Clinical consequences of FD?
CHD, peripheral arterial disease
What lipoprotein is affected with familial hypertriglyceridemia (FHTG)
Etiology of FHTG?
TG level in FHTG?
Clinical consequence of FHTG?
None really, but if these people are obese or drink a lot etc, more likely to have problems
What lipoprotein is affected with SEVERE FHTG?
Chylomicrons and VLDL
TG level in severe FHTG?
Etiology of severe FHTG
Physical findings in severe FHTG
Clinical significance of severe FHTC?
Pancreatitis (linked to large elevation in TGs)
Lipoprotein with an apo(a) that hangs off of Apo-B and is a major genetic risk factor for CHD and is homologous to plasminogen
Epidemiologically, levels of HDL have what relationship to CHD?
Where is HDL made?
HDL comes from macrophages which have lots of free cholesterol. ABCA1 allows free cholesterol to add to nascent HDL.
Sits on nascent HDL and esterifies cholesterol allowing HDL to become mature and return to the liver
Mutation in apoA1 gene (role in biogenesis and formation of HDL) causes nascent HDL to be nonfunctional and be catabolized rapidly
-leads to rapid removal of nascent HDL particle before mature assembly
Clinical outcomes of apoA1 mutations
Low HDL, no increased risk for CVD
ABCA1 mutation causing faulty transport of free cholesterol from macrophages into HDL. Have a buildup of cholesterol in macrophages and low HDL
Clinical outcomes of tangier disease
Low HDL, no inc risk for CVD
Mutation in LCAT gene means that cholesterol cannot be deposited into the center of HDL causing a buildup of free cholesterol
Physical findings of LCAT deficiency
Cholesterol gets deposited in cornea