Lipid Homeostasis and antihyperlipidemic drugs Flashcards
1
Q
Lipids
A
- Free Fatty acids, cholesterol and triglycerides that are synthesized within cells or from dietary fat
2
Q
Cholesterol
A
- Fluidity, cell growth and viability
- precursor for vit D and bile salts
3
Q
Triglycerides
A
- Synthesized in the liver ad supplies energy and fuel to muscles
4
Q
Pathway 1 : Dietary cholesterol enter
A
- Enters in intestine from diet enters micellar membrane
- Absorbed and transported to liver where it is mixed with hepatic cholestero
5
Q
Pathway 2: How is cholesterol absorbed
A
- From micelles into intestinal wall via protein channel (NPC 1L1) on electrolyte plasma membran
6
Q
Pathway 3: Bile emulsification
A
- Emulsify dietary lipids and facilitate absorption
- Bile salts are the recycled via hepatic portal vein
7
Q
ATP-binding removal of cholesterol
A
- Immediately pumped out of body into the intestinal lumen
- Heterodimeric transporter protein ABCG5/G
8
Q
De novo synthesis
A
- Synthesis in the liver 70-80%
- Synthesis in small intestine 10%
- HMG-CoA reductase which a highly membrane bound enzyme catalyze rate limit step in sterol and isoprenoid biosynthesis to produce Cholesterol
9
Q
Lipid homeostasis
A
- Cholesterol and triglyceride are insoluble in water so transported by carrier protein (lipoprotein)
10
Q
Lipoprotein
A
- Central core containing cholesterol ester (hydrophobic)
- Triglyceride surrounded by free cholesterol phospholipids
- Apolipoproteins facilitate lipoprotein formation
11
Q
Function of Apolipoprotein
A
- Serve a structural role
- Ligand for lipoprotein receptor
- Guiding the formation of lipoprotein
serving as activator inhibitor involved in metabolism of lipoproteins
12
Q
HDL
A
- Anti-atherogenic size low density is high
13
Q
LDL
A
- Pro-atherogenic as it has a larger size and lower density
14
Q
Chylomicrons
A
- Large triglyceride-rich particles made by intestine - transport triglycerides and cholesterol to peripheral tissue & liver
15
Q
Chylomicron remants
A
- Removal of triglycerides from chylomicron by peripheral tissue small remnants
16
Q
Very LDL
A
- Produced in the liver and are triglyceride rich
17
Q
Intermediate density lipoproteins
A
- Removal of triglycerides from VLD & adipose forming IDL which is enriched in cholesterol
18
Q
Low density lipoprotein formation and function
A
- LDL is produced from VLDL and IDL
- LDL is enriched with cholesterol
- LDL carry most of cholesterol in circulation
- Contain one APO B-100 particle
- High level of APOB-100 causes risk of atherosclerosis
19
Q
Hypertriglyceridemia
A
- Abundance of LDL and low levels of HDL, obesity and type 2 diabetes
20
Q
sLDL
A
- Decrease affinity for LDL receptor therefore large concentration of LDL in blood
- Easily enter arterial wall binding and causing arterial legions
- sLDL more susceptible to oxidation so more macrophages are recruited therefore inflammation occurs
21
Q
High-density lipoproteins
A
- Contain cholesterol and phospholipids
- Apo A-1 is core protein multiple
- High levels of Apo A-1 linked to decreased risk of atherosclerosis
22
Q
Functions of HDL
A
- Stimulates macrophage cholesterol efflux collecting removes no plate development
- Anti-inflammatory
- Decreases LDL oxidation
- Anti-apoptotic
23
Q
Most important role of HDL
A
- Reverse cholesterol transport cholesterol transport making HDL ani-atherogenic
24
Q
Lipid homeostasis
A
- Exogenous lipoprotein pathway incorporates dietary lipids to chylomicrons in intestine
- Triglycerides carried in chylomicrons are metabolized in adipose tissue by lipoprotein lipase
Release of fatty acids which are metabolized by muscle and adipose leave chylomicron remnants
25
Q
In the liver lipid homeostasis
A
- Formation of VLDL in the liver
- Triglycerides carried in VLDL are metabolized in muscle by lipoprotein lipase release free fatty acids and IDL
- IDL is metabolized into LDL and is taken up by LDL receptor in tissues such as liver
26
Q
Reverse cholesterol transport
A
- Excess cholesterol from cells is bought back to the liver by HDL
- Formation of nascent HDL in liver. Then acquire the cholesterol and phospholipids effluxed from cell by ABCA1forming mature HDL
27
Q
Pathophysiology of atherosclerosis
A
- Endothelial dysfunction
- Formation of lipid layer or fatty streak within the intima
- Migration of leukocytes and smooth muscles into the vessel wall
- Foam cell formation
- Degradation of extracellular matrix
28
Q
Factors that effect oxidized LDL
A
- Stress, smoking, obesity and fat diet enhance conversion causing inflammation
- Platelets recruit sit on endothelial layer
29
Q
Hyperlipidemia
A
- Abnormally high levels of fat include cholesterol and triglycerides
30
Q
Lipid lowering
A
- Cholesterol synthesis inhibition
- Intestinal absorption
- Lipoprotein lipase activity
- HDL
31
Q
Cholesterol synthesis inhibition
A
- Statin completely inhibits HMG-CoA reductase leading to reduced cholesterol
- Compensation for cholesterol level the liver recruits more LDL for circulation
32
Q
Side effects of cholesterol synthesis inhibition
A
- GI disturbances
- Skeletal muscle myopathy
33
Q
Anion exchange resins
A
- Cholestyramine and colestipol bind with bile salts and excreted in feces
- Unpalatable, digestive problems, interfere with fat soluble nutrients and drug
34
Q
Lipoprotein Lipase inhibition
A
- Fibrates elicit complex effects on circulating effects (fenofibrate)
- First line for hypertriglyceridemia
- Combine fibrate and statin greater effect
35
Q
Increase HDL level in circulation
A
- Nicotinic acid receptor antagonist reduces circulation VLDL and LDL and increase HDL
- Side effect tachycardia, itching, nausea and vomiting
36
Q
Coronary circulation
A
- Two tiny arteries leaving out of aorta
- Profuse blood into myocardium
- Handle high pressure
- Thickening of internal surfaces of arteries cause ischemia
