Pharm 19 and biochem 34 Flashcards
__________ are macromolecular aggregates that transport triglycerides and cholesterol in the blood
Lipoproteins
What is the largest and least dense class of lipoproteins
Chylomicrons
What are the smallest and most dense lipoprotein class
HDLs
What lipoproteins contains the highest proportion of proteins
HDLs
_____ are amphipathic proteins that intercalate into the surface coat of lipoproteins
Apolipoproteins
What determines the metabolic fate of the lipoprotein
Apolipoprotein content
What apoprotein is a ligand for the LDL receptor
ApoB100
What apolipoproteins does HDL serve as a reservoir for
The exchangeable apolipoproteins in the plasma, including apoAI, apoCII and apoE
What is the primary function of apoB-containing lipoproteins
Deliver fatty acids in the form of triglycerides to muscle tissue for use in ATP biogenesis and to adipose tissue for storage
Where are chylomicrons formed
Intestine
Where are VLDL particles formed
Liver
What is a key regulatory event that differentiates chylomicron metabolism from VLDL metabolism
Editing of apoB mRNA
What is apoB editing complex-1 (apobec-1) expressed within
Enterocytes but not hepatocytes
What constitutes the catalytic subunit of the apoB editing complex
Apobec-1
What results when the there is deamination of the cytosine of the apoB mRNA molecule to uridine
Nucleotide is converted from a glutamine to a premature stop codon
Lipid absorption into the enterocytes of the duodenum and jejunum is facilitated mainly by _______
Micelles
What are long-chain fatty acids and monoglycerides taken up departed into the enterocyte and re-esterified to form triglycerides by
DGAT
What are medium-chain fatty acids absorbed directly into
Portal blood
How do dietary and biliary cholesterol from micelles enter the enterocyte
Via a protein channel named Niemann-pick C1-like protein (NPC1L1)
What protein is involved in the immediate pumping back into the lumen of cholesterol (some of it)
ABCG5/8
What do hepatocytes synthesize triglycerides in response to?
Increased free fatty acid flux to the liver
What in hepatocytes lipidates apoB100 to form nascent VLDL particles
MTP
Where is apoB48 Synthesized
Intestine
Where is apoB100 synthesized
Liver
What must chylomicrons and VLDL acquire before they can bind to LPL
ApoCII
What occurs when chylomicrons and VLDL can bind to LPL
Hydrolyzing of triglycerides from the core of the lipoprotein
What controls the rate of lipolysis of chylomicron and VLDL triglycerides
ApoCIII, which is an inhibitor of LPL activity
What are apoAI and apoCII transferred to HDL in exchange for?
ApoE
What apolipoprotein serves as a high-affinity ligand for receptor-mediated clearance of the particles
ApoE
What does cholesterol activate (enzyme) in order to increase esterification and storage of cholesterol in the cell
ACAT
What does PCSK9 do
It is a secreted protein that binds the LDL receptor, promoting its degradation
Where does HDL formation mainly occur
Liver
What does ABCA1 do
Incorporates a small amount of membrane phospholipid and unesterified cholesterol into the apoAI molecule
What does PLTP do
Transfers phospholipids from the surface coat of apoB-containing remnant particles to the surface coat of HDL
What 2. Transporters are mainly involved in mediating phospholipid and cholesterol secretion
ABCB4 (for phospholipids) and ABCG5/8 for cholesterol
What is another name for statins
HMG-CoA reductase inhibitors
What does SREBP2 do
Transcription factor that upregulates expression of the gene encoding the LDL receptor
What does increased level of SREBP2 cause
Increased uptake of plasma LDL, and consequently decreases plasma LDL cholesterol concentration
What is the least potent statin
Fluvastatin
What statins are metabolized by p450 SA4
Lovastatin, simvastatin, and atorvastatin
Who should nice acid sequestrants be used with caution with
In patients with hypertriglyceridemia
Who are inhibitors of bile acid absorption mainly used for
Treatment of hypercholesterolemia in young and in patients form whom statins alone did not provide sufficient plasma LDL reduction
Why are plant sterols useful
They have similar molecular structure to cholesterol but are more hydrophobic (displace cholesterol from micelles, increasing the excretion of cholesterol in the stool)
How does ezetimibe decrease cholesterol transport from micelles into enterocytes
By selectively inhibiting cholesterol uptake through a brush border protein, NPC1L1
What do fibrates do
Bind to and activates PPARalpha
What happens to PPARalpha once it binds with fibrate
Heterodimerizes with retinoids X receptor (RXR)
What is the end result of fibrates
Results in numerous changes in lipid metabolism that act collectively to decrease plasma triglyceride levels and increase plasma HDl
What are fibrates indicated for the use of
Treatment of hypertriglyceridemia as well as hypertriglyceridemia with low HDL
What does niacin do
Decreases plasma LDL-cholesterol and triglyceride concentrations and increases HDL cholesterol
What is the major adverse affect of niacin
Cutaneous flushing and prutitis
What is the most effective agent available for raising HDL
Niacin
what protein is required for reverse cholesterol transport and the biogenesis of HDL
ABCA1
what NPC1L1 believed to do
transport cholesterol into cells via an absorptive endocytotic mechanism, involving the protein clathrin
what do SREBPs specifically do
specifically enhance transcription of the HMG-CoA reductase gene by binding to the sterol-regulatory element (SRE) upstream of the gene
what is cholesterol ester production in the liver catalyzed by
acyl-CoA-cholesterol acyl transferase (ACAT)
what does ACAT catalyze
the transfer of a fatty acid from coenzyme A to the hydroxyl group on carbon 3 of cholesterol
what is the rate limiting step of the synthesis of bile salts
7-alpha-hydroxylase
what are the primary bile salts
cholic acid and chenodeoxycholic acid
what are some secondary bile salts
deoxycholic acid and lithocholic acid
what apoprotein activates LPL
apoCII
what does apoAI do
activates LCAT; structural component of HDL
what apoprotein may regulate transfer of apoproteins from HDL to other lipoprotein particles
apoAII
what apoprotein may be involved in assembly of HDL and chylomicrons
ApoAIV
what is the role of ApoB48
assembly and secretion of chylomicrons from small bowel
what is the role of apoB100
VLDL assembly and secretion; structural protein of VLDL, IDL, and LDL; ligand for LDL receptor
what apoprotein may inhibit hepatic uptake of chylomicron and VLDL remnants
ApoCI
what apoprotein is the cofactor activator of LDL
apoCII
what is the apoprotein that is the ligand for binding of several lipoproteins to the LDL receptor, to the LRP
apoE
what is the function of chylomicron remnants
return dietary lipids to the liver
what is the function of VLDL
deliver endogenous lipids
what is the function of IDL
return endogenous lipids to the liver; precursor of LDL
what is the role of LDL
deliver cholesterol to the cells
what does LCAT do
catalyzes the transfer of fatty acid from the 2-position of lecithin (phosphatidylcholine) in the phospholipid shell of the particle to the 3-hydroxyl group of cholesterol, forming a cholesterol ester
describe region one of the LDL receptor
LDL-binding domain
describe region 2 of the LDL receptor
epidermal growth factor-like domain; transducin-beta-subunit-like domain
describe region 3 of the LDL receptor
N-linked oligosaccharide domain
describe region 4 of the LDL receptor
O-linked oligosaccharide domain
describe region 4 of the LDL receptor
transmembrane domain
describe region 6 of the LDL receptor
intracellular (Cytostolic) domain
