Lipid Homeostasis and antihyperlipidemic drugs Flashcards
(36 cards)
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
In the liver lipid homeostasis
- 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
Reverse cholesterol transport
- 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
Pathophysiology of atherosclerosis
- 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
Factors that effect oxidized LDL
- Stress, smoking, obesity and fat diet enhance conversion causing inflammation
- Platelets recruit sit on endothelial layer
29
Hyperlipidemia
- Abnormally high levels of fat include cholesterol and triglycerides
30
Lipid lowering
- Cholesterol synthesis inhibition
- Intestinal absorption
- Lipoprotein lipase activity
- HDL
31
Cholesterol synthesis inhibition
- Statin completely inhibits HMG-CoA reductase leading to reduced cholesterol
- Compensation for cholesterol level the liver recruits more LDL for circulation
32
Side effects of cholesterol synthesis inhibition
- GI disturbances
- Skeletal muscle myopathy
33
Anion exchange resins
- Cholestyramine and colestipol bind with bile salts and excreted in feces
- Unpalatable, digestive problems, interfere with fat soluble nutrients and drug
34
Lipoprotein Lipase inhibition
- Fibrates elicit complex effects on circulating effects (fenofibrate)
- First line for hypertriglyceridemia
- Combine fibrate and statin greater effect
35
Increase HDL level in circulation
- Nicotinic acid receptor antagonist reduces circulation VLDL and LDL and increase HDL
- Side effect tachycardia, itching, nausea and vomiting
36
Coronary circulation
- Two tiny arteries leaving out of aorta
- Profuse blood into myocardium
- Handle high pressure
- Thickening of internal surfaces of arteries cause ischemia
