Lipid Metabolism Flashcards
Chylomicrons contain mostly _______. Which apolipoprotein is found on their surface?
mostly triglycerides, apo-B48
Apolipoproteins A-I and A-II are structural proteins of _____.
HDL
After ingestion of fats, _________ enter lacteals –> lymph –> systemic circulation.
chylomicrons
What happens to chylomicrons shortly after they get into the systemic circulation?
The apo-CII on their surface binds to LPL on muscle/adipose cells to hydrolyze TAGs –> FFAs to give to the cells; the chylomicron then becomes a chylomicron remnant, which is then taken up by the liver via an apo-E receptor.
What are the two major pathways of triglyceride transport?
Intestinal pathway, hepatic pathway
What is the composition of a VLDL? Which apolipoproteins are found on VLDLs?
Mostly TAGs, some cholesterol esters. Apo-B100, E, and C-II
Which apolipoprotein is a cofactor for lipoprotein lipase?
C-II
Which apoprotein binds to the chylomicron remnant receptor on hepatocytes?
Apo-E
Synthesized in the ________ (an organ), VLDLs are released into the blood and deliver FFAs to cells via membrane bound ________ (an enzyme on cell plasma membranes), turning the VLDL into a(n) _______. What are the possible fates of this lipoprotein?
Synthesized in the liver, VLDLs deliver FFAs to cells via lipoprotein lipase. Once enough triglycerides have been given to cells such that TAGs = CEs in the lipoprotein, it becomes an IDL. The IDL can then be endocytosed by a hepatocyte via LDL-R and (B-100 binds to it) or it can give more triglycerides to hepatocytes via hepatic TAG lipase and become an LDL (mostly cholesterol).
Name two primary diseases of hyperlipidemia.
- Familial hypertriglyceridemia
2. Familial combined hyperlipidemia
Describe the biochemical problem involved in familial hypertriglyceridemia.
For some reason, too many TAGs are made in the liver and packaged in to big-ass VLDLs.
Describe the biochemical problem involved in combined familial hyperlipidemia.
Too many apo-Bs are made so the liver makes a bunch of VLDLs to put them on. Result is increased triglycerides AND cholesterol.
What would be the consequence of a defective lipoprotein lipase?
Chylomicrons would be unable to give triglycerides to cells –> increased chylomicrons and triglycerides in the blood
What would be the consequence of a defective apo-CII?
Same as a defective LPL, cuz CII binds to LPL so chylomicrons (and VLDLs) can give triglycerides to cells.
Which apo-E allele type has the highest affinity for the remnant receptor? What is the consequence of being an E2/E2 genotype?
E4 allele has highest affinity. E2 allele has the lowest, so E2/E2 genotypes have impaired remnant uptake –> increased remnants in plasma and low LDL levels. Hyperlipidemia (remnant removal disease) occurs in these people if another defect is added (inherited or acquired).
Which lipids are elevated in remnant removal disease? What interesting physical exam finding might a patient have?
Both cholesterol and triglycerides are elevated because VLDLs and chylomicron remnants will be elevated due to an apo-E defect. Therefore, both cholesterol and triglycerides are elevated.
What would you expect of a lipid profile in a patient with familial hypertriglyceridemia? What about familial combined hyperlipidemia?
Hypertriglyceridemia: for some reason too many triglycerides are put into VLDLs –> triglyceridemia only.
Familial combined hyperlipidemia: overproduction of apo-B –> overproduction of VLDLs that contain both TAGs and cholesterol esters –> increased levels of triglycerides AND cholesterol.
What effect does insulin resistance have on lipoprotein lipase?
Insulin resistance impairs the action of LPL
What type of lipid disorders are eruptive xanthomas associated with?
Hypertriglyceridemia seen in chylomicronemia, familial hypertriglyceridemia, or a combo of one of these plus diabetes.
Highly elevated cholesterol levels are associated with what skin findings?
Tendon xanthomas - often seen in the achilles tendon and extensor tendons of the hand.
What is the molecular defect involved in familial hypercholesterolemia?
Defective LDL receptor
What is the mechanism of action of PCSK9 inhibitors?
These increase the half-life of LDL receptors –> increased LDL uptake.
What is the inheritance pattern of familial hypercholesterolemia?
Autosomal dominant
What is the mechanism of action of PCSK9 inhibitors?
Inhibit PCSK9 –> more LDL receptors –> more uptake of LDL
