anti-hyperlipidemics #1 Flashcards
Major Lipids - Cholesterol
- essential component of cell ___
- precursor to __ -and ___
- membranes
- sterols, steroids
Major Lipids - Triglyceride (triacylglycerol)
- ___ form of fuel to support generation of high energy compounds
- component of ___ lipids
- storage
- structural
Major Lipids
Both cholesterol and triglycerides are transported in blood in ___ aggregated known as ___
macromolecular, lipoproteins
Lipoprotein
- transport ___ and ___ in blood
- surface made of ___ , free ___ , and ___
- core made of ___ and cholesterol ___
- ___ on surface are critical in regulating transport and metabolism
- lipoprotein lipase system: release free ___ from lipoproteins
- cholesterol, triglycerides
- phospholipids, cholesterol, protein
- triglyceride, ester
- apoproteins
- fatty acids
Lipoproteins
classes are based on ___ , composition, and electrophoretic ___
- chylomicrons: transport of ___ lipids from gut to liver and adipose tissue
- VLDL: secreted by ___ into blood as a source of ___
- IDL: ___ depleted VLDLs
- LDL: main ___ form in blood
- HDL: secreted by __ and aquire ___ from peripheral tissues and atheromas ( ___ cholesterol transport)
density, mobility
- dietary
- liver, triglycerides
- triglycerid
- cholesterol
- liver, cholesterol, reverse
Important Apolipoproteins
ApoA-1 - structural ___; ligand of ___ receptor
- mediates ___ cholesterol transport
- produced in ___ and ___
ApoB-100 - structural VLDL, IDL, LDL ; ___ receptor ligand
- produced in the ___
ApoB-48 - structual in ___
- produced in the ___
ApoE - Ligand for ___ remnant receptor. ___ cholesterol transport with HDL
- produced in ___ and other tissues
ApoCII - found in ___, VLDL
- binds to lipoprotein lipase to adhance ___ hydrolysis
- HDL, ABCA1
- reverse
- liver, intestine
- LDL
- liver
- chylomicrons
- intestine
- LDL
- chylomicrons
- TG
LPL ( ___ lipase) - in capillaries of fat, cardiac and skeletal muscle
HL ( ___ lipase) - produced in liver, key in converting ___ to ___
- lipoprotein
- hepatic
Lipid Absorption and Transport
Exogenous Pathway:
- dietary cholesterol converted to ___ in intestine
- ___ breaks it down to ___ remnants
- remnant receptor on ___ converts it to ___ and ___
- chlomicrons
- lipoprotein lipase, chylomicron
- liver, cholesterol, bile acids
Lipid Absorption and Transport
- liver makes ___
- this is converted to ___ by ___ lipase
- It is then converted into ___ by ___ lipase
- ___ can either be taken up by receptors on the liver, extrahepatic tissues, or it can be ___
- if taken up by the extahepatic tissues, it is converted to ___
- if ___ it is picked up by macrophges and turned into ___ cells
- VLDL
- IDL, lipoprotein
- LDL, hepatic
- LDL, oxidized
- HDL
- oxidized, foam
Liver Synthesis of CHolesterol
1) acetoacetyl CoA is converted to HMG-CoA by ___ synthase
2) HMG-CoA is converted to mevalonate by ___ reductase
3) squalene, lansterol, cholesterol
___ synthesis is the major source of cholesterol. ___ synthesis is most critical to total body burden
HMG-CoA
HMG-CoA
de novo
liver
Lipoprotein Disorders
lipoprotein disorders are detected by measuring lipid in serum after a ___ hr fast
- ratio of TC to HDL is key in assessing risk of CVD
- ratio > ____ is assocaited with increased risk
- less or equal to ___ is desirable, ratio of less than ___ is optimal
10 hr
4.5
3.5
3
diseases associated with lipoprotein disorders
Hyperlipoproteinemia
___ - excess accumulation of cholesterol in vascular smooth muscle
- ___ coronary artery disease
- neurologic disease - ___
Hypertriglyceridemia
- Pancreatitis
- ___ - lil fat pockets under the skin
- Increased risk of CHD
artherosclerosis
premature
stroke
xanthomas
Atherosclerosis
initial stage: fatty ___
accumulated ___
streaks
plaques
Subendothelial uptake of Cholesterol by Macrophages
initiated by ___ accumulation
LDL
Goals of therapy
- decrease reabsorption of excreted ___
- decrease secretion of ___ from liver
- decrease synthesis of ___
- increase hydrolysis of ____ ___, specific for lowering ___
each 10% reduction in cholesterol levels is asociated with ___ - ___ % reduction in incidence of coronary heart disease
- bile acids
- VLDL
- cholesterol
- lipoprotein triglycerides, triglycerides
- 10-30%
antihyperlipidemic drugs
drugs mainly for high cholesterol
- ___ ___ binding resins
- inhibitors of cholesterol ___ and ___
- ___ inhibitors
- ___ inhibitors
- bile acid
- absorption, synthesis
- PCSK9
- MTTP
antihyperlipidemic drugs
Drugs mainly for high triglycerides (3)
- fibrates
- niacin
- omega 3 fatty acids
Bile Acid-Binding Resins
MOA: inhibit ___ of bile acids from intestine by binding bile acids to form ___ complex excreted in the ___
- ___ LDL receptors in the liver
- ___ molecular weight polymers (resins) that exchange ___ ion for bile acids
- ___ (Queastran) and ___ (Colestid)
reabsorption, insoluble, feces
- up-regulate
- large, chloride
- cholestyramine, colestipol
Ezetimibe (Zetia)
___ absorption inhibitor
- MOA: inhibits ___ absorption of ___ and ___ from dietary sources and reabsorption of cholesterol excreted in ___
- inhibits ___
cholesterol
- intestinal, cholesterol, phytosterols, bile
- NPC1L1
Neimann-Pick C1-Like1
NPC1L1 Cholesterol Transporter
expressed on the ___ surface of enterocytes in the ___.
apical
small intestine
HMG-CoA Reductase Inhibitors - Statins
mimic ___ acid moiety
- prodrugs: ___ and ___
Examples:
- fluvastatin ( ___ )
- ___ (Crestor)
- atorvastatin ( ____ )
- ___ (Mevacor)
- simvastatin ( ___ )
- ____ ( Pravachol)
- pitavastatin ( ___ )
mevalonic
- lovastatin, simvastatin
- Lescol
- rosuvastatin
- Lipitor
- lovastatin
- Zocor
- pravastatin
- Livalo
HMG-CoA Reductase Inhibitors
MOA: ___ inhibit HMG-CoA ___ , the rate limiting enzyme in cholesterol biosynthesis
- ____ LDL receptors, enabling more LDL delivered to liver (reducing plasma cholesterol)
competitively, reductase
- up-regulate
HMG-CoA Reductase Inhibitors - upregulation of hepatic LDL receptors
T or F: when there are a lot of sterols, SREBP will leave the ER to go to the golgi. It will cleave and part will go to the nucleus to amp up the trancription of LDL receptors
FALSE; when there are no sterols, this happens
thats why statins increase hepatic LDL uptake
