Anti-hyperlipidemic drugs

Question 1

Importance of cholesterol metabolism

Question 2

Major lipids

Answer 2

-cholesterol
-triglyceride

-transported in blood as lipoproteins

Question 3

Cholesterol

Answer 3

-essential component of cell membranes
-precursor to sterols and steroids

Question 4

Triglyceride (triacylglycerol)

Answer 4

-storage form of fuel to support generation of high energy compounds
-component of structural lipids

Question 5

Lipoprotein

Answer 5

-transport cholesterol and tgs in blood
-spherical particles w phospholipid, free cholesterol and protein making up surface
-core made of tg and cholesterol ester
-apoproteins on surface critical in regulating transport and metabolism
-lipoprotein lipase system

Question 6

Lipoprotein lipase systems

Answer 6

-release free fatty acids from lipoproteins

Question 7

Lipoprotein structure

Answer 7

-apoprotein on surface (regulation)
-surface: phopholipid, protein, and cholesterol
-core: tg and cholesterol ester

Question 8

Classes of lipoproteins (largest to smallest)

Answer 8

-Chylomicrons
-VLDL
-IDL
-LDL
-HDL

-based on density, composition and electrophoretic mobility

Question 9

Chylomicrons

Answer 9

-transport dietary lipids from gut to liver and adipose tissue
-mostly tg structure

Question 10

VLDL

Answer 10

-very-low
-secreted by liver into blood as source of tgs
-mostly tgs

Question 11

IDL

Answer 11

-intermediate
-tg-depleted VLDLs

Question 12

LDL

Answer 12

-low
-main cholesterol form in blood
-mostly cholesterol

Question 13

HDL

Answer 13

-high
-secreted by liver and acquire cholesterol from peripheral tissues and atheromas (reverse cholesterol transport)

Question 14

Centrifugation

Answer 14

-slide 10

Question 15

important apoliproteins

Answer 15

-ApoA-I
-ApoB-100
-ApoE
-ApoCII

Question 16

ApoA-I

Answer 16

-structural in HDL
-ligand of ABCA1 receptor
-mediates reverse cholesterol transport!
-produced in liver and intestine

Question 17

ApoB-100

Answer 17

-structural in VLDL, IDL, LDL
-LDL receptor ligand
-produced in liver

Question 18

ApoB-48

Answer 18

-structural in chylomicrons
-produced in intestine!

Question 19

ApoE

Answer 19

-ligand for LDL remnant receptor
-reverse cholesterol transport w HDL!
-produced in liver and other tissues

Question 21

ApoCII

Answer 21

-chylomicrons and VLDL
-binds to llipoprotein lipase to enhance tg hydrolysis

Question 21

Lipid absorption and transport

Answer 21

-slide 12

Question 21

Lipoprotein lipase (LPL) found in

Answer 21

-capillaries of fat
-cardiac and skeletal muscle

Question 22

Hepatic lipase (HL) found in

Answer 22

-produced in liver
-convert IDL to LDL!!

Question 22

oh boy

Answer 22

slide 13

Question 25

Cholesterol synthesis

Answer 25

-liver most critical to total body burden
-de novo is major source
-acetoacetyl CoA + acetylCoA to cholesterol

Question 26

Cholesterol synthesis steps

Answer 26

1. acetoacetyl CoA + acetyl CoA
   -HMG-CoA synthase
2. hydroxymethylglutaryl-CoA
   -HMG-CoA reductase + 2 NADPH
3. Mevalonate
4. IPP + DMAPP
5. GPP + IPP
6. FPP + squalene
7. Lanosterol
   -19steps
8. cholesterol

Question 27

Diseases from lipoprotein disorders

Answer 27

-hyperlipoproteinemia
-hypertriglyceridemia

Question 28

Hyperlipoproteinemia

Answer 28

-artherosclerosis (accumulation of cholesterol in vascular smooth muscle)
-premature CAD
-stroke

Question 29

Hypertriglyceridemia

Answer 29

-pancreatitis
-xanthomas
-inc risk of CHD

Question 30

Deadly duo

Answer 30

-artherosclerotic plaque + thrombosis
-plaque rupture