Flashcards in Lipid Metabolism, Dyslipidemias and Treatment 1 Deck (30):
1. Explain the role of lipoproteins in atherogenesis
LDL is essential for the formation of atheroma, their migration into the sub endothelial space and subsequent modification and phagocytosis by macrophages leads to the inflammatory response seen in atheroma formation.
1. Why are lipoproteins important in understanding coronary heart disease?
dylipidemia is one of the risk factors for CHD, and it shows a positive correlation with the risk of CHD mortality; adult humans experience contextually high levels of blood lipids and lipoproteins which leads to disease
2. Contrast lipoprotein and lipoprotein particle.
lipoprotein particles are spherical with a nonpoloar TG and cholesterol esters coated in polar unesterified cholesterol, phospholipids and apolipoproteins (plasma lipids circulate in lipoprotein particles)
apoplipoprotins stabilize lipoprotein particles, impart solubility to lipoproteins, catalyze changes in particle composition and facilitate entry/exit into/from cells
3. Explain the difference between lipoproteins and lipids.
lipids are the molecules that are carried inside lipoprotein particles, cholesterol and TG are lipids and once they are combined with apoplipoproteins, they are considered a lipoprotein particle
Describe a chylomicron.
very low density lipoprotein made of mostly triglycerides (90-96%) that are traveling from the gut in the blood stream, they carry apoplipoproteins B-48 (coming from the intestine) and CII (activator of lipoprotein lipase)
a very low density lipoprotein made of 60% triglycerides and carrying the apoproteins B-100 (made in the liver), E and C-II
intermediate density lipoprotein (need not know anything more)
low density lipoprotein that is made of 50% cholesterol, carries the B-100 apoplipoprotein (made in the liver)
high density lipoprotein, containing only 20% cholesterol and apoplipoprotein A-I and A-II
Atherogenicity is determined by the _____ and ______ of lipoproteins.
concentration and the size
Explain why all abnormalities in plasma lipid concentrations "dyslipidemias" are really "dyslipoporteinemias."
lipids (cholesterol, tryglycerides) are only surrogate markers for lipoproteins
HDL cholesterol, LDL cholesterol and triglycerides are surrogate measures for what?
HDL- C: surrogate for number of HDL particles
LDL-C: surrogate for LDL particles (usually calculated using the Friedewald equation)
TG: surrogate for number of VLDL particles
Under what circumstances can the LDL measure be misleading/ inaccurate as calculated by Friedewald equation?
less accurate as TG levels increase, since the assumption that TG/5= VLDL-C breaks down
misleadingly low when small LDL particles are present
At the same level of LDL-C, people with small, dense LDL have about ____ more particles than those with large LDL.
Explain why the size of lipoprotein particles is important.
Large LDL and HDL particles can carry more cholesterol than small LDL and HDL particles, the problem arises with increasing number of lipoprotein molecules, not necessarily with increasing total cholesterol (although there is a vague correlation)
the number of LDL particles interacting with the arterial wall drives the disease, not the the cholesterol within, the size of LDL particles modulates the risk
4. Explain the key steps in the endogenous lipoprotein pathway involving lipids from the gut.
1. lipids from the gut are transported in a chylomicron (with apo B48, apoC and apo E
2. chylomicron undergoes lipolysis by LPL creating a HDL and chylomicron remnant (IDL)
3. chylomicron remnant can be cleared from the body by the liver via remnant receptor binding
4. Explain the key steps in the endogenous lipoprotein pathway involving lipids from the liver.
1. liver produces VLDL with apo B-100, apo C and apo E
2. lipolysis by LPL creates an IDL which is metabolized by hepatic triglyceride lipase into LDL
3. LDL can be taken up by the liver via LDL receptors or be deposited in tissues.
Apo B, E, and B/E receptors are all the same receptor, they are also know by the following names:
LDL and chylomicron remnant receptor
Cholesterol from the diet and bile enters the small intestine and is absorbed via a ______ _____ .
sterol transporter (unabsorbed cholesterol is excreted in the feces)
Chylomicron remnants, LDL and IDL are taken up by the hepatic ______ receptor (CYM, LDL) or ______ receptor related protein. (CYM, IDL)
LDL receptor, or to a lesser extent LDL receptor-related protein
Excess cholesterol that is delivered to back to the liver via HDL particles, which are taken up by hepatic ____.
4. Bile is reabsorbed in the intestine by ____ ___ ____ transporter. After absorption some cholesterol can be exported back from the enterocyte into the intestinal lumen by the _____ transporter (_____)
intestinal bile acid transporter; ABC transporter (ABCG5/G8
4. Within enterocytes, cholesterol is esterified with fatty acids via ____-___ _____ _____ and absorbed fatty acids are also used to synthesize ___ ___ and ___ in the enterocyte.
acyl-CoA cholesterol acyltransferase (ACAT)
TG and phospholipids
Through the activity of __ ____ ____ cholesterol esters are packaged with TG phopholipids and apolipidprotein B-48 into chylomicrons.
microsomal transfer protein (MTP)
Chylomicrons acquire apo E and apo CII during transport to the liver, these apoplipoproteins are required for what actions of the lipoprotein particle?
LPL of endothelial cells requires apoC to hydrolyze TG
chylomicron remnants are cleared from the circulation by binding of apo E to to the hepatic LDL receptor or LDL receptor related protein (some evidence that they can also be taken up by the aerial wall where they can contribute to atherogenesis)
How are LDL formed?
LDL are formed from the depletion of TG from IDL due to hydrolysis by LPL (apoC and a poE play similar roles in the metabolism of chylomicrons and VLDL)
Cholesterol leaves the liver via 2 routes, name them
secretion in the form of VLDL (most of which is returned to the liver in the form of LDL)
excretion into the bile
The liver controls cholesterol balance by regulating two things, name them.
regulating excretion of cholesterol into the bile
regulating the amount of cholesterol that is taken up by altering LDL receptors
(50% of body pool cleared daily)
How are levels of LDL receptor expressed altered?
regulated by diet, hormones, genetics, medications
expression suppressed by cellular cholesterol, stimulated by cholesterol depletion, insulin and T4