Hyperlipidemia Flashcards
Macromolecule complexes that transport lipids of human plasma
Lipoproteins
Metabolic disorders that involve an increase in levels of any of the lipoprotein species
Hyperlipoproteinemias or Hyperlipidemias
Increased levels of triglycerides in plase
Hyperlipidemia
Marked hyperlipidemia causes life-threatening…
Acute pancreatitis
Spherical particles with hydrophobic core regions containing cholesteryl esters and triglycerides. Unesterified cholesterol, phospholipids, and apoproteins surround the core
Plasma lipoproteins
This lipoprotein contains very high molecular weight B-48 apoproteins (ApoB-48)
Chylomicrons
Where is ApoB-48 formed?
Intestines
Is VLDL a very low-density molecule, intermediate-density, or low-density?
Very low-density
Is IDL a low-density molecule, intermediate-density, or low-density?
Intermediate-density
Is LDL a low-density molecule, intermediate-density, or low-density?
Low density
What lipoproteins contain very high-molecular weight B-100 apoproteins (ApoB-100)?
VLDL, IDL, LDL
Where is ApoB-100 synthesized?
Liver
Proved structural stability to the lipoproteins
apoproteins
A number of apoproteins function as ________ in lipoprotein-receptor interactions or as ________ in enzymatic processes that regulate lipoprotein metabolism
ligands; cofactors
Formed in the intestine and carry triglyerides of dietary origin, cholesterol, and cholesteryl esters
Chylomicrons
The triglycerides are removed from the chylomicrons in _________ tissues
extrahepatic
Triglycerides in chylomicrons are hydrolyzed by what enzyme to free fatty acids?
lipoprotein lipase
Where is VLDL secreted from?
Liver
VLDL exports ________ to peripheral tissues
triglycerides
Where is IDL formed from?
VLDL
Some IDL are endocytosed directly by the ______; the rest are converted to ______ by further removal of triglycerides
liver; LDL
What mediates the removal of triglycerides in IDL?
LPL and hepatic lipase
How is LDL formed?
from VLDL (via IDL)
Which lipoprotein delivers cholesterol to hepatocytes and other cells?
LDL
Catabolism of LDL in hepatocytes and other cells involves ________________
receptor-mediated endocytosis
__________ from the LDL core are hydrolyzed, yielding free cholesterol which is used for the synthesis of cell membranes
Cholesteryl esters
High-density lipoproteins that exert antiatherogenic effects
HDL
They retrieve cholesterol from the artery wall and peripheral tissues that inhibit the oxidation of atherogenic liproteins
HDL
Where does much of the lipid in HDL come from during lipolysis?
Chylomicrons and VLDL
HDL can deliver cholesteryl esters directly to the liver via the ____________ which does not endocytose the lipoproteins
Scavenger Receptor (SR-BI)
Where is cholesterol synthesized?
Hepatocytes
How is cholesterol synthesized in the hepatocytes?
via the HMG-CoA reductase pathway
Cholesterol is exported from the hepatocytes to the general circulation via ________
VLDL
Hepatocytes are capable of eliminating cholesterol by secretion of cholesterol in the bile and by converting cholesterol to _______
bile acids
Which class of drugs is the first choice and are the most effective in reducing LDL levels?
HMG-CoA reductase inhibitors (Statins)
HMG-CoA reductase enzyme converts HMG-CoA to ______ (cholesterol biosynthesis)
mevalonate
The statins are _______ inhibitors of HMG-CoA reductase enzyme and ______ of HMG-CoA intermediates
competitive, structural analogs
Statins inhibit the ________ synthesis of cholesterol, leading to a decrease in cholesterol levels
de novo
Niacin is also known as ______
Vitamin B3
Modifies all plasma lipoproteins and lipids favorably
Niacin
Niacin is promoted for the treatment of _______
hypertriglyceridemia
Niacin inhibits ______ secretion from the hepatocytes, which leads to a decrease in the production of LDL
VLDL
Niacin inhibits the intracellular lipase of adipose tissue via receptor-mediated signaling, which leads to (increase or decrease?) in the flux of free fatty acids to the liver
decrease
The inhibition of intracellualr lipase reduces ______ production in the liver
VLDL
Niacin ________ the clearance of VLDL via the LPL pathway, which leads to a decrease in triglyceride levels
induces
Does Niacin increase or decrease the catabolic rate for HDL?
decrease
Name the fibric acid derivatives
Gemfibrozil
Fenofibrate
Fenofibric Acid
Do fibric acid derivatives decrease or increase the levels of VLDL in plasma?
decrease
Fibric acid derivatives lower ____________ by 30-50% and may increase _______ cholesterol
triglycerides; HDL
When fibric acid derivatives decrease elevated triglycerides, LDL cholesterol may increase or decrease?
increase
Which fibric acid derivative is the only fibrate with demonstrated beneficial effects on CV outcomes
Gemfibrozil
Fibrates are useful in hypertriglyceridemias in which ________ predominate
VLDL
Which drugs bind to PPAR-alpha and induce lipolysis of VLDL triglycerides via LPL, which results in a decrease in VLDL levels?
Fibric Acid Derivatives
What is cholesterol metabolized in the liver to?
Bile acids
Where are bile acids excreted to via the bile?
intestine
Where are bile acids efficiently reabsorbed?
jejunum and ileum
Are bile acid sequestrants soluble or insoluble in water?
insoluble
Name the bile acid sequestrants
Colestipol
Cholestyramine
Colsevelam
Name the selective inhibitor of intestinal absorption of both dietary and biliary cholesterol and phytosterols
Ezetimibe
What is the target for Ezetimibe?
a transport protein (NPC1L1) for cholesterol and phytosterols (plant sterols)
What is Ezetimibe’s primary clinical effect?
reduction of LDL levels in plasma
Which class of drugs is Ezetimibe synergistic with in reducing LDL-cholesterol levels?
statins
Name the Omega-3 polyunsaturated fatty acids (PUFA) (fish oil)
Lovaza
Vascepa
What are the two most important omega-3 PUFAs?
Eicosapentaenoic Acid (EPA) Docoshaexanoic Acid (DHA)
Which omega-3 PUFA contains the ethyl esters of both EPA and DHA?
Lovaza
Which omega-3 PUFA contains only EPA as the ethyl ester?
Vascepa
What is the MOA of omega-3 PUFAs?
They decrease triglyceride levels by reducing hepatic triglyceride production and increasing triglyceride clearance
Name the antisense oligonucleotide
Mipomersen
Mipomersen is an antisense oligonucleotide inhibitor of?
ApoB-100 synthesis
What is the principal apoprotein in LDL and VLDL lipoproteins?
ApoB-100
__________ is a synthetic strand of nucleic acid, binds to mRNA that encodes ApoB resulting in degradation or disruption of the mRNA. This leads to a decrease in the synthesis of ApoB and a decrease in the synthesis of VLDL and LDL
Mipomersen
Decreased synthesis of VLDL and LDL leads to a (increase or decrease?) in plasma levels of LDL-cholesterol
decrease
Name the Microsomal Triglyceride Transfer Protein (MTP) Inhibitor
Lomitapide
What drug is both a substrate and an inhibitor of CYP3A4? It is also an inhibitor of the active-efflux transporter P-glycoprotein (P-gp)
Lomitapide
Lomitapide is contraindicated for use with other inhibitors of _________
CYP3A4
Where is microsomal triglyceride transfer protein (MTP) located?
in the lumen of the ER of hepatocytes and enterocytes
What is the function of MTP?
the assembly/formation of ApoB-containing lipoproteins in the liver and intestine
What binds to and inhibits MTP?
Lomitapide
Since Lomitapide inhibits MTP and the synthesis of chylomicrons and VLDL, what is the result?
LDL will not be synthesized from VLDL, leading to a significant reduction in plasma levels of LDL-cholesterol.
What is transcriptionally regulated by the content of cholesterol on the cell?
Production of LDL receptors and HMG-CoA reductase enzyme
Increased plasma levels of LDL can result from?
Increased secretion of VLDL, increased levels of IDL, decreased LDL catabolism and decreased LDL receptors
Cholesterol is delivered to the liver by
LDL, HDL, remnants of VLDL and chylomicrons
Fibric acid derivatives are ____ for ____
ligands, PPAR-alpha
Which omega-3 PUFAs are poor substrates responsible for triglyceride synthesis and inhibit esterification of other fatty acids?
EPA and DHA
