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54 Cards in this Set

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Roles of fatty acids (2)
1) components of more complex membrane lipids & 2) components of stored fat in the form of triacylglycerols
Describe the structural features of fatty acids
1) even numbers of carbons
2) cis-double bonds only, separated by 1 carbon
3) defined by omega (start numbering form the last carbon)
Essential fatty acids (definition and 2 examples)
Humans cannot produce them (must get from diet) omega-3 and omega-6
Structure of triacylglycerols
glycerol + 3 fatty acids
Structure of glycerophospholipids
Glycerol + 2 fatty acids + PO4-X (polar)
What are the two membrane lipids discussed in lecture?
Glycerophospholipids and sphingolipids
Structure of sphingolipids
Sphingosine + non polar side chain+ fatty acid+ PO4+ choline or (mono/oligo) saccharide
What is the main function of cholesterol?
To modulate the fluidity of membranes by interacting with their complex lipid components
How are cholesterol esters different from free cholesterol?
1) less polar than free cholesterol and are preferred for transport in plasma and storage & 2) packed into lipid particles
Do cholesterol esters contribute to membranes?
NOOO
Where is the ester of cholesterol esters located?
Where the 3B -OH normally is
How are cholesterol esters synthesized from cholesterol?
1) Cholesterol + phosphatidylcholine, 2) | LCAT (lectithin cholesterol acyltransferase) & 3)Cholesterol Ester + lysophosphatidylcholine
Are the BC and CD rings of cholesterol trans or cis fused?
TRANS
A-I is key apoprotein for which lipoprotein?
HDL
B-100 is key apoprotein for which lipoprotein?
LDL
HDL is made mostly of?
proteins
What is LDL mostly made of?
Cholesterol
What is VLDL mostly made out of?
Triglycerides
Chylomicrons are made mostly of?
Triglycerides
Primary functions of lipoproteins (2)
1) Associate highly insoluble lipids with more polar ones like cholesterol and phospholipids, 2) Provide a trafficking mechanism for hydrophobic small molecules
Which lipoprotein transports TG from intestines to other tissues?
Chylomicrons
Do chylomicrons transport TG to kidneys?
NO
Which lipoprotein transports TG to fat tissues?
VLDL
Which lipoprotein transports cholesterol to peripheral tissues?
LDL
Which lipoprotein transports cholesterol to the liver?
HDL
Which lipoprotein is bound to plasma cholesterol?
HDL
Are the chylomicrons part of the exogenous or endogenous pathway?
EXOGENOUS- because carries TG from intestines.
What is the only "nonexchangeable" apoprotein?
B-100
What is the function of B-100?
lipid recognition and binding to LDL particle
How does HDL transfer the cholesterol and cholesterol esters into the liver?
It binds to scavenger receptor B1 (SR-B1) in hepatocytes
Three stages of cholesterol biosynthesis
1) Squalene generation from Acyl-CoA, 2) Cyclization of squalene to lanosterol, & 3) Conversion of lanosterol to cholesterol
What is the enzyme that converts (S) B-hydroxyl-B-methylglutaryl-CoA to (R)-mevalonic acid?
HMG-CoA Reductase
What is the function of HMG-CoA reductase?
Converts (S) B-hydroxyl-B-methylglutaryl-CoA to (R)-mevalonic acid in Step 1 of cholesterol biosynthesis (squalene production)
What are the 4 strategies for controlling hyperlipidemia?
1) diet, 2) biosynthesis, 3) bile acid sequestration, 4) lipoprotein catabolism
Mechanism of action of fibrates
Agonists of PPAR alpha
What are the effects of fibrates?
Decreases serum TG and VLDL
What are phenolic ethers?
Fibrates
PPAR alpha
Peroxisome proliferator activated receptor alpha (fibrates agonize it)
Name the two fibrate prodrugs
Clofibrate and Fenofibrate
What is the mechanism of action of bile acid sequestrants?
"positively charged nitrogen atoms sequester bile acid reabsorption, when the body senses lower bile, degrades cholesterol to make more"
Effects of bile acid sequestrants
Lower serum LDL
Properties of bile acid sequestrates (3)
1) Anion exchange resins, 2) water insoluble and inert to digestive enzymes, & 3) not absorbed through the GI tract
What is Ezetimibe's mechanism of action?
Ezetimibe inhibits the sterol influx transporter of the intestine, NPC1L1, preventing the absorption of cholesterol from the diet.
Effects of Ezetimibe
reduces serum LDL and increases HDL
NPC1L1
a sterol influx transporter located in the apical membrane of the enterocyte (inhibited by Ezetimibe)
Mechanism of action of statins
Mimics the product of HMG-CoA reductase to prevent cholesterol biosynthesis (step 1)
Fungal metabolite statins (3)
Lovastatin, Pravastatin, & Simvastatin
Synthetic Statins (4)
Fluvastatin, Cerivastatin, Atorvastatin, & Rosuvastatin
Which fungal metabolite accumulates faster in peripheral tissues?
Pravastatin
Why isn't cerivastatin used anymore?
It had the highest bioavailability, which also meant it had the highest incidence of side effects, most notably rhabdomyolysis or weakening of skeletal muscle
Do the fungal or synthetic metabolites have chiral centers?
Fungal- complex in nature
Pravachol (aka)
Pravastatin
Lipitor (aka)
Atorvastatin
Which class has a decalin?
The statins