Cholesterol Lab , Athersclerosis and thrombosis

Question 1

Describe the difference between a fat and a lipid

Question 2

List the main types of fats found in food - give the number of fatty acids in each

Answer 2

• Triglcyerides (Triacylgylcerols, or TAGS), composed of 3 fatty acids
• Phospholipids - 2 fatty acids
• Cholesterol -1 fatty acids

Question 3

What is the functional group of a fatty acid?

Answer 3

Carboxyl group

Question 4

How many double bonds are present in the following types of fatty acids:

Saturated

Unsaturated

Monounsaturated

Polyunsaturated

Answer 4

Saturated: None

Unsaturated: 1+

Monounsaturated: 1
Polyunsaturated: 1+

Question 5

Compare structure of trans and cis fatty acids

Answer 5

Cis: both hydrogens either side of a double bond are on the same side

Trans: Hydrogens are on opposite sides from each other

Question 6

Give examples of saturated, Cis-unsaturated (mono and polyunsaturated), and trans-unsaturated fats

Answer 6

Saturated fats - Cheese

Cis-unsaturated - Nuts, Olive oil

Trans-unsaturated - biscuits, deep friend foods

Question 7

Most lipids circulate through the bloodstream as lipoproteins, why? Also describe the structrue of lipoproteins

Answer 7

Since most lipids are not water soluble

• Lipid-protein complexes that contain a CORE of insoluble glycerides (fatty acid + alcohol ester)
• There is a superficial coating of phospholipids and proteins that make the entire complex soluble
  
  • ​Exposed proteins on the surface of the complex bind to specific membrane receptors - allowing the proteins to determine what cells will absorb the asssociated lipids
  • These surface proteins are called APOPROTEINS
    
    • They provide structural integrity as well as mediating which cells will uptake the lipids inside

Question 8

List the main lipoproteins in the plasma, in order of increasing protein density

Answer 8

• Chylomicrons
• VLDL
• IDL
• LDL
• HDL

Question 9

What lipids do Chylomicrons carry?Where do they transport these lipids to and from ? Where are they produced?

Rememeber this question is is effectively the exogenous pathway of cholesterol transport

Answer 9

• Carry mainly triglycerides from diet, although can be small levels of cholesterol and lipids
• Produced by the intestinal epithelial cells
• Chylomicrons are hydrolyzed by an endolthelial lipoprotein lipase in the capilalries of muscle and fat tissue - HDL is also produced as a by-product of this
  
  • The chyclomicron rememnants will then arrive at the Liver, by binding to LDL receptors
  • The remaining triglycerides are removed, and any Cholesterol that was in the chylomicron along with synthesised cholesterol or recycled cholesterol picked up by HDL, are packed into VLDLs
  • Any cholesterol that is not packaged into VLDLs will be used by the liver to make Bile salts - excess cholesterol will be excreted in bile, meaning it can be used again

THIS IS EFFECTIVELY THE EXOGENOUS PATHWAY

Question 10

Describe the endogenous lipoprotein pathway (VLDL and LDL)

Answer 10

• VLDLs are made from liver triglycerides and cholesterol (either from the exogenous pathway, or self-synthesized)
• VLDLs travel to peripheral tissues where triglycerides are hydrolyzed by the endothelial cells and are taken up as fatty acids
• Now that there are less triglycerides, the VLDL remanents are now referred to as IDL
  
  • These IDLs return to the liver from the periphery and are hydrolyzed by hepatic lipase, leading to further decrease in tryglyceride content
  • Now, we have LDL particles that predominately contain cholesterol
• LDLs are released into blood, and can be absorbed by cells expressing LDL-Receptor

Question 11

Explain the role of HDL in cholesterol metabolism

Answer 11

• HDL geenrated in the liver
• These can pick up free cholesterol that is released by cells who have excess cholesterol, or dying cells which release cholesterol and return it to the liver

Question 12

Explain how LDL can lead to Athersclerosis

Answer 12

• The endothelium will have been damaged in some way before this occured - usually the barrier function is comprimisd
• LDL can be taken up by endothelial cells, where it can enter the intima
  
  • ​Since there proteoglycans in the underlying smooth muscle, it is possible that LDLs can be retained in the intima - increasing the likelyhood that they could become oxidised
• There is evidence that LDLs must become oxidised to be harmful and is what promotes the immune and inflammatory reactions that characterize atherosclerosis - what actually causes Oxidation is unknown ​
  
  • ​thought that inflammatory response can be mediated against oxLDLs, as they can trigger the endothelia cells to produce cytokines
  • It is thought this is what may attract monocytes into the vessel walls, where they transform into macrophages
• Once this LDL has become oxidised, it is thought that it may enter macrophages via Scavenger receptor - causing the macrophage to become bloated and form a foam cell
• Furthermore, growth factors such as PDGF and FGF are released, causing UNDERLYING SMOOTH MUSCLE cells to migrate to the area underneath endothelilal cells
• These smooth smooth muscle cells will prolfierate make collagen, forming a fibrous layer underneath the intima

Question 13

GIve normal values for Total, LDL and HDL and triacylglycerol

Answer 13

Question 14

GIve biological uses for cholesterol

Answer 14

• Important for cell membrnae structure
• Important for Vitamin D formation

Question 15

What are the afffects of different types of dietary fats on LDL levels

Answer 15

• Saturated fats increase LDL
• Monounsaturated and polyunsaturated DECREASE LDL

Question 16

Explain the mechanisms as to how different dietary fats affect LDL levels

Answer 16

• Cells have LDL receptors - if cholesterol levels fall in these cells, they will express more LDL receptor, in this we are talking about Liver cells
• ACAT plays a role generating cholesterol esters from free cholesterol - which means levels of cholesterol will be lower in the cell - To do this, ACAT likes to use Unsaturated fats
• ACAT Is not as happy using Saturated fats as a substrate, therefore much less cholesterol is converted into cholesterol esters - this means LDL receptors are not upregulated, LDL cholesterol therefore remains in circulation in higher levels

Question 17

Describe how thrombus formation at the site of an athersclerotic plaque can lead to occlusion of the coronary artery and acute myocardial infarction

Answer 17

• Plaques are commonly found at coronary arteries
• These plaques as they become bigger can become more unstable -

Question 18

Define myocardial infarction, referring to NSTEMI and STEMI

Answer 18

• When blood supply to heart is so restricted that there is myocardial death.

NSTEMI: Partial occlusion of coronary artery that leads to heart muscle death

STEMI: Full occlusion of coronary artery that leads to heart muscle death

Question 19

Explain the differences in ECG readings between NSTEMI and STEMI

Answer 19

Question 20

Draw the expected appearance of an NSTEMI and a STEMI