*Pharmacology - lecture 5 (science, drugs are in table)

Question 1

Are lipids soluble or insoluble in water?

Answer 1

Insoluble (or sparingly soluble)

Question 2

Purpose of lipids?

Answer 2

Essential for membrane biogenesis and membrane integrity

Energy sources, precursors for hormones and signalling molecules

Question 3

How are non-polar lipids (e.g. cholesterol esters and triglycerides) transported in blood?

Answer 3

Within lipoproteins e.g. high density lipoproteins, low density liporpteins

Question 4

In terms of HDL and LDL, what is CV disease strongly associated with?

Answer 4

Elevated LDL

Decreased HDL

Question 5

What causes elevated LDL and decreased HDL?

Answer 5

Diet and lifestyle (particularly western)
Genetic factors (e.g. familial hypercholestrerolaemia)

Question 6

What are the 2 parts of a lipoprotein?

Answer 6

Hydrophobic core

Hydrophilic coat

Question 7

What is found within the hydrophobic core of a lipoprotein?

Answer 7

Esterified cholesterol and triglycerides

Question 8

What is the hydrophilic coat of a lipoprotein composed of?

Answer 8

Monolayer of amphipathic cholesterol, phospholipids and one, or more, apoproteins (apo)

Question 9

What are the major lipoproteins? (4)

Answer 9

HDL particles
LDL particles
Very-low density lipoprotein particles
Chylomicrons

Question 10

What apoproteins do HDL proteins contain? (2)

Answer 10

apoA1 and apoA2

Question 11

What apoprotein does LDL particles contain?

Answer 11

apoB-100

Question 12

What apoprotein does very-low density lipoprotein particles contain?

Answer 12

apB-100

Question 13

What apoprotein does chylomicrons contain?

Answer 13

apoB-48

Question 14

What is the purpose of apoB-containing lipoproteins?

Answer 14

Deliver triglycerides to muscle for ATP biogenesis and adipocytes for storage

Question 15

Where are chylomicrons formed?
What do they carry?
What is this pathway called?

Answer 15

In intestinal cells
Transport dietary triglycerides
Exogenous pathway

Question 16

Where are VLDL formed?
What do they carry?
What is this pathway called?

Answer 16

Liver cells
Triglycerides synthesised in that organ
Endogenous pathway

Question 17

What are the 3 stages of the life cycle of an ApoB-containing liposome?

Answer 17

Assembly
Intravascualr metabolism
Receptor mediated clearance

Question 18

Where does the majority of the bodies cholesterol come from?

Answer 18

75% = liver
25% = diet

Question 19

What happens to an chylomicron formed within the endoplasmic reticulum of an enterocyte?

Answer 19

It exits the enterocyte by exocytosis following the addition of a second apoprotein (apoA1), enters lymphatics and is carried in lymph to systemic circulation (subclavian vein) via the thoracic duct

Question 20

What are VLDL particles containing triglycerides assembled in the liver hepatocytes from?

Answer 20

Free fatty acids derived from adipose tissue (particularly during fasting) and de novo synthesis

Question 21

What must happen to activate chylomicrons and VLDL particles allowing them to target triclyceride delivery to adipose and muscle tissue?

Answer 21

They must be activated by by the transfer of apoCII from HDL particles

Question 22

What is the name of the enzyme that is associated with the endothelium of capillaries in adipose and muscle tissue?

Answer 22

Lipoprotein lipase (lipolytic enzyme)

Question 23

What facilitates the binding of chylomicrons and VLDL to LPL on the endothelium of capillaries in adipose and muscle tissue?

Answer 23

ApoCII

Question 24

What does lipoprotein lipase do?

Answer 24

Hydrolyses core triglycerdies to free fatty acids and glycerol which enter tissues

Question 25

What is name of particles depleted of triglycerides (But still containing cholesterol esters)?

Answer 25

Chylomicron and VLDL remnants

Question 26

Why do chylomicrons and VLDL particles become relatively enriched in cholesterol?

Answer 26

Due to triglyceride metabolism due to LPL

Question 27

What happens to ApoCII when the chylomicrons and VLDL dissociated from LPL?

Answer 27

It is transferred to HDL particles in exchange for apoE which is high affinity ligand for receptors mediated clearance - particles are now remnants

Question 28

What happens to remnants?

Answer 28

They return to the liver and are further metabolised by hepatic lipase - all apoB48-containing remnants and 50% of apo100 containing remnants are cleared by receptor-mediated endocytosis into hepatocytes - remaining apoB100-containing remnants loose further triglyceride through hepatic lipase, come smaller and enriched in cholesterol ester and via intermediate density lipoproteins (IDL) become LDL particles asking ape and retaining solely apoB100

Question 29

What is the most important place of LDL particle clearance?

Answer 29

the liver

Question 30

Where is the most important site of LDL clearance?

Answer 30

Liver

Question 31

What does cellular uptake of LDL occur by?

Answer 31

Receptor mediated endocytosis

Question 32

How is cholesterol released once within the liver at the lysosome?

Answer 32

By hydrolysis

Question 33

What does release of cholesterol within the liver cause?

Answer 33

Inhibition of HMG-CoA reductase (rate limiting enzyme in de novo cholesterol synthesis) Down regulation of LDL receptor expression Storage of cholesterol as cholesterol ester

Question 34

How does an atheromatous plaque form?

Answer 34

Uptake of LDL from the blood into the intima of the artery LDL subsequently oxidised to atherogenic oxidised LDL Migration of monocytes across the endothelium into the intimate where they become macrophages Uptake of oxidised LDL by macrophages converts them to cholesterol laden foam cells that form a fatty streak Release of inflammatory substances from various cell types causes division and proliferation of smooth muscle cells into the intimate and the deposition of collagen The formation of an atheromatous plaque consisting of a lipid core (product of dead foam cells) and a fibrous cap (smooth muscle cells and connective tissue)

Question 35

What is the only place in the body that has the capacity to eliminate cholesterol from the body?

Answer 35

Liver

Question 36

Why are HDLs good?

Answer 36

They have a key role in removing excess cholesterol from cells by transporting it in plasma to the liver - only the liver has the ability to eliminate cholesterol

Question 37

Where is HDL mainly formed?

Answer 37

In the liver

Question 38

What is the name for the initial structure of HDL when formed in the liver?

Answer 38

pre-betaHDL

Question 39

What is the structure of pre-BetaHDL?

Answer 39

ApoA1 in association with a small amount of surface phospholipid and unesterified choelsterol

Question 40

What does pre-betaHDL mature to?

Answer 40

Alpha-HDL

Question 41

Where does disc-like pre-beta-HDL mature to spherical alpha-HDL?

Answer 41

In the liver

Question 42

What happens when pre-betaHDL matures to alpha-HDL?

Answer 42

Surface cholesterol is enzymatically converted to hydrophobic cholesterol ester that migrates to the core of the particle

Question 43

What is reverse cholesterol transport?

Answer 43

Mature HDL accepts excess cholesterol from the plasma membrane of cells and delivers cholesterol to the liver

Question 44

What receptor does HDL interact with at the liver?

Answer 44

Scavenger receptor-B1 (allows the transfer of cholesterol and cholesteryl esters into hepatocytes)

Question 45

What mediates transfer of cholesterol esters from HDL to VLDL and LDL in the plasma?

Answer 45

Cholesterol ester transfer protein (indirectly return cholesterol to the liver)

Question 46

What is primary dyslipidaemia?

Answer 46

That which occurs through a combination of diet and genetic factors

Question 47

What is secondary dylipidaemia?

Answer 47

A consequence of another rids ease e.g. type II diabetes, hypothyroidism, alcoholism, liver disease