Lipids

Question 1

Why do we care so much about lipids?

Answer 1

Single most modifiable risk factor for heart disease

Question 2

Lipid Defintion

Answer 2

any group of organic compounds - insoluble in water and soluble in organic solvents

Question 3

Classes of Lipids

Answer 3

Fats
Waxes and Oils
Sterols 
Fatty Acids 
Triglycerides 
Phospholipids

Question 4

Transport of Lipids in Blood

Answer 4

Free FA transported w/ proteins

Albumin major carrier

Question 5

Lipoproteins

Answer 5

Lipids transported as lipoproteins

• Composed of non-polar core (triglycerides and cholesteryl esters)
• Surface Layer: phospholipids + cholesterol
• Apoliproteins (protein component -helps w/ binding)

Question 6

4 LIPOPROTEIN Classifications

Answer 6

Chylomicrons - from intestinal cells into systemic circulation through the lymphatic duct - TGS from FA and glycerol-rebuilt in intestinal cells and then packaged into chylomicrons and into circulation

VLDL-liver

LDL-formed from VLDL in plasma-so basically liver
-Bad cholesterol

HDL-reverse cholesterol transport
-Good cholesterol

Question 7

Order lipoproteins in order (light to heavy)

Answer 7

Chylo b/c contain triglycerides which are lighter
Then VLDL
IDL
LDL - what makes it heavier is the cholesterol
HDL

Question 8

Orogin of the lipoproteins

Answer 8

Intestine - chylomicrons 
Liver - VLDL 
Liver -IDL 
Liver-LDL 
HDL - from many tissues

Question 9

Composition of Chylomicrons

Answer 9

Mostly TGs

Question 10

Composition of VLDL

Answer 10

Cholesterol and TGs

Question 11

Composition of IDL

Answer 11

Almost equal cholesterol, TGS, phosphlipid and proteins

Question 12

LDL-

Answer 12

Choesterol mainly and less TGs

Question 13

HDL

Answer 13

Almost 50% Protein

Question 14

Apoliproteins on Each Lipo

Answer 14

Chylo-C,B-48, E and A
VLDL-b100, C and E
IDL-B100, E 
LDL-B100 
HDL-ACE

Question 15

B100 Apoliportien Role

Answer 15

Responsbile for binding of LDL receptor-if can’t bind - will accumulate to toxic concentration

Question 16

Lipoprotein Metabolism

Answer 16

Tissues have LDL receptor - LDL lipoprotein used to shuffle cholesterol
If cells need cholesterol, can up regulate receptor and take more

Adipocytes- TG hydrolysis and and FA will be incorporated into adipocytes - will be resyntehsized to TGs for long-term storage

Question 17

Chylomicron Metabolism

Answer 17

From intestine - will give free FA to adipose or muscle , some synthesis to HDL, and CM remnant to livr

Normal people - should have rise and lower chylomicrons - should be cleared

Question 18

VLDL metabolism

Answer 18

Synthesized by liver
Metabolised by LPL to form glycerol and FFA
Then converted to IDL and LDL
Used by many tissues

Question 19

LDL uptake

Answer 19

LDL w. B100 receptor binds to LDL receptor

Ingested by cell and cholesterol is released `

Question 20

HDL metabolism and reverse cholesterol transport

Answer 20

Have HDL
Uptakes tissue cholesterol
Delivers to liver
Before thought this would be cure for high cholesterol but didn’t work in clinical trials

Question 21

2 Outcomes from Arethrosclerosis

Answer 21

1. Grow so big to cause Angina - chest pain
2. Plaque inside arterial wall -can rupture and is very thrombogenic - huge blockage in artery which leads to heart attack

Question 22

Relationship b/w CHD and LDL

Answer 22

Direct correlation

Question 23

Modifiable Risk Factors for Heart Disease

Answer 23

1. hyperchoesterolaemia
2. hypertension
3. cigarette smoking
4. diabetes
5. low HDL
6. hypertriglycerdemia

Question 24

Non modifiable Risk Factors for Coronary Heart Disease

Answer 24

CVD history
Male
Age

Question 25

LDL and Factors That Affect It

Answer 25

Increase w/ age Decrease w/ exercise Gender Equal

Question 26

TGs and Factors that Affect It

Answer 26

``` Age Alcohol Females less than Males Obesity Estrogens ```

Question 27

Who to screen for cholesterol?

Answer 27

Every man and woman 40 years and older If have other risk factors-screen earlier and more aggressively

Question 28

When to screen

Answer 28

3-5 years for men and women b/w 40 and 75 in primary prevention Whenever risk status changes Every year in secondary prevention

Question 29

How to screen

Answer 29

Measure total cholesterol, TG, LDL, and HDL HDL is good biomarker of protecting against CVD risk

Question 30

Cholesterol Treatment

Answer 30

Statin HMG-CoA reductase Inhibitor HMG-CoA to Melvalonate is rate limiting step - When inhibit - cells can't make cholesterol by themselves -Will up regulate receptor and bring in cholesterol so get decrease of cholesterol in the blood

Question 31

What lipids do we measure and How

Answer 31

Can be fasting or non-fasting Avoid alcohol > 72 hours before b/c alcohol can increase TG concentration for up to 72 hours Test total cholesterol, LDL, HDL, Tgs and can measure ApoB and ApoA1

Question 32

Measuring cholesterol

Answer 32

Basic measurement Cheap Form a dye that can be measured using spectrophotometry ( 500nm) -Cholesterol esters --> form cholesterol- which then forms cholesterol -Cholesterol w/ cholesterol oxidase forms 2 compounds -H202 then forms a dye that is 500nm

Question 33

HDL measurements

Answer 33

Shielding agent addition - blocks all interactions w/ all the lipoproteins except for HDL -So then only HDL will react w/ cholesterol esterase + cholesterol oxidase

Question 34

Measuring TGs

Answer 34

Spectrophotometric Assay Will hydrolyze TGS in glycerol and Free Fas w. a LIPASE Will get a colour change when take glycerol + ATP and react w/ glycerokinase

Question 35

LDL measurement

Answer 35

``` Friedwald eqn -LDL = Total - (HDL + TG/2.2) -cant be used if tg>2.2 Now can measure LDL directly - but more expensive - ```

Question 36

Why TG/2.2

Answer 36

IDL is transient and shouldn't have chylo b/c person is fasting - So end up getting LDL and VLDL - VLDL are an estimate of TG - So can get LDL

Question 37

Apo ad ApoA1

Answer 37

ELISA and immunophelometric ELISE better -but immuno used more Rarely use b/c inertia to convert form measuring LDL to ApoB