Flashcards in Lipid Metabolism Deck (28):
Briefly describe the exogenous lipid pathway
Dietary lipids enter the small intestine and are bound by chylomicrons containing ApoC, ApoE, ApoB-48, etc. and these travel through the intestine where LPL strips free fatty acids (which then go to muscle and adipose tissue).
The smaller remnant chylomicron (atherogenic) then goes to the liver and is taken up via the LDL receptor.
Briefly describe the endogenous lipid pathway
Chylomicron (10:1 TG:CHOL) remnants deliver fatty acids, etc. to the liver where they are re-esterified into TAGs and then packaged into VLDL (5:1 TG:CHOL) containing ApoB-100, ApoE, and ApoC that transports it to the body from the liver.
What is IDL?
Intermediate density lipoprotein (1:1 TG:CHOL) which is made after fatty acids and some cholesterol are stripped off endogenous VLDL. Contains ApoB-100 and ApoE but ApoC has been stripped. This is highly atherogenic as well
What happens to IDL?
it is acted upon by hepatic lipase and the remaining TAGs are stripped leaving a cholesterol rich LDL (less than 5% TAG) molecule.
What is the role of HDL?
to transport cholesterol back to the liver to complete the cycle
What happens if too much LDL is circulating?
some is taken up by peripheral tissue like vessel walls causing atherosclerosis
Write out the Friedewald Formula.
LDL = TC - HDL - TG/5.0 (mg/dL)
What does ApoCII do?
cofactor for lipoprotein lipase (LPL)
What does ApoCIII do?
inhibits LPL so high levels leads to hypertriglyceridemia
What is primary chylomicronemia?
defective removal of CM caused by a apoCII or LPL defect leading to elevated levels of chylomicrons, VLDL elevation, and pancreatitis (common anytime VLDL gets over 1000)
What is the treatment for primary chlyomicronemia?
take the fat out of the diet and replace with medium chain fats that can be broken down without chylomicrons
What is familial hypertriglyceridemia?
defective metabolism of VLDL (LPL defect common) leading to elevated VLDL, pancreatitis, hyperTAG
What is familial dysbetalipoproteinemia?
defective metabolism of VLDL via ApoE defect (activates hepatic lipase) (E2/E2 alleles) in which VLDL can be metabolized to IDL but the IDL then sticks and cant be metabolized
cholesterol and TAG will both be increased
What does familial dysbetalipoproteinemia lead to?
elevated VLDL, IDL, and CM remnants leading to elevated cholesterol and atherosclerosis
How is familial dysbetalipoproteinemia tested?
give the patient a statin which usually lowers LDL but these patients don't have much LDL so nothing happens
What is familial combined hyperlipidemia (FCH)?
overproduction of apoB-100 so VLDL is being pumped out too quick and both VLDL and LDL become elevated leading to premature atherosclerosis
MOI of FCH?
What is familial hypercholesterolemia (FH)? Are TAG levels elevated?
LDL receptor or ApoB defect leading to decreased receptor levels so LDL cannot be cleared effectively leading to high cholesterol
hyperTAGemia is not invariably present (TAGs should be normal here)
What should total cholesterol levels be?
less than 200 mg/dL
What should LDL cholesterol levels be?
less than 130 mg/dL
What should TAG levels be?
less than 120 mg/dL
What should HDL levels be in men? women?
greater than 40 for men
greater than 50 for women
What are some secondary causes of hyperlipidemia?
-kidney disease (nephrotic)
-liver disease (hepatitis, biliary disease)
Why would nephrotic syndrome lead to hyperlipidemia?
albumin suppresses VLDL production
What kinds of meds could cause hyperlipidemia?
-estrogen (increases TAGs)
What do high doses of b-blockers and thiazide diuretics do?
block the function of lipoprotein lipase and increase TAG levels
What are the principle dietary factors that increase LDL?
cholesterol and saturated and trans-fats (red meat, dairy products, cheese, pastries, baked goods)