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Study Notes - Cardiology > *Pharmacology - lecture 5 (science, drugs are in table) > Flashcards

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

1
Q

Are lipids soluble or insoluble in water?

A

Insoluble (or sparingly soluble)

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2
Q

Purpose of lipids?

A

Essential for membrane biogenesis and membrane integrity

Energy sources, precursors for hormones and signalling molecules

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3
Q

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

A

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

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4
Q

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

A

Elevated LDL

Decreased HDL

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5
Q

What causes elevated LDL and decreased HDL?

A 
Diet and lifestyle (particularly western)
Genetic factors (e.g. familial hypercholestrerolaemia)
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6
Q

What are the 2 parts of a lipoprotein?

A

Hydrophobic core

Hydrophilic coat

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7
Q

What is found within the hydrophobic core of a lipoprotein?

A

Esterified cholesterol and triglycerides

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8
Q

What is the hydrophilic coat of a lipoprotein composed of?

A

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

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9
Q

What are the major lipoproteins? (4)

A

HDL particles
LDL particles
Very-low density lipoprotein particles
Chylomicrons

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10
Q

What apoproteins do HDL proteins contain? (2)

A

apoA1 and apoA2

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11
Q

What apoprotein does LDL particles contain?

A

apoB-100

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12
Q

What apoprotein does very-low density lipoprotein particles contain?

A

apB-100

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13
Q

What apoprotein does chylomicrons contain?

A

apoB-48

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14
Q

What is the purpose of apoB-containing lipoproteins?

A

Deliver triglycerides to muscle for ATP biogenesis and adipocytes for storage

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15
Q

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

A

In intestinal cells
Transport dietary triglycerides
Exogenous pathway

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16
Q

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

A

Liver cells
Triglycerides synthesised in that organ
Endogenous pathway

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17
Q

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

A

Assembly
Intravascualr metabolism
Receptor mediated clearance

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18
Q

Where does the majority of the bodies cholesterol come from?

A 
75% = liver
25% = diet
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19
Q

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

A

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

20
Q

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

A

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

21
Q

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

A

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

22
Q

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

A

Lipoprotein lipase (lipolytic enzyme)

23
Q

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

A

ApoCII

24
Q

What does lipoprotein lipase do?

A

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

25
Q

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

A

Chylomicron and VLDL remnants

26
Q

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

A

Due to triglyceride metabolism due to LPL

27
Q

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

A

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

28
Q

What happens to remnants?

A

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

29
Q

What is the most important place of LDL particle clearance?

A

the liver

30
Q

Where is the most important site of LDL clearance?

A

Liver

31
Q

What does cellular uptake of LDL occur by?

A

Receptor mediated endocytosis

32
Q

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

A

By hydrolysis

33
Q

What does release of cholesterol within the liver cause?

A

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

34
Q

How does an atheromatous plaque form?

A

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)

35
Q

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

A

Liver

36
Q

Why are HDLs good?

A

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

37
Q

Where is HDL mainly formed?

A

In the liver

38
Q

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

A

pre-betaHDL

39
Q

What is the structure of pre-BetaHDL?

A

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

40
Q

What does pre-betaHDL mature to?

A

Alpha-HDL

41
Q

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

A

In the liver

42
Q

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

A

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

43
Q

What is reverse cholesterol transport?

A

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

44
Q

What receptor does HDL interact with at the liver?

A

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

45
Q

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

A

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

46
Q

What is primary dyslipidaemia?

A

That which occurs through a combination of diet and genetic factors

47
Q

What is secondary dylipidaemia?

A

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

Study Notes - Cardiology (25 decks)

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