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Metabolism, Endocrinology And Haematology > Lipid Transport > Flashcards

Lipid Transport Flashcards

1
Q

Give examples of different classes of lipids

A
  • fatty acids
  • cholesterol
  • TAGS
  • phospholipids
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2
Q

Why must lipids be carried in the plasma in association with another protein ?

A

Because lipids are insoluble

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3
Q

What are the two examples of ways lipids are carried in plasma ?

A

1) 98% of lipids are carried by lipoprotein particles
2) 2% of lipids ( mainly fatty acids) are carried in plasma by albumin.

ALL lipids are non-covalently bound

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4
Q

Where do we get majority of cholesterol from ?

A

Most cholesterol is synthesised In the liver

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5
Q

Cholesterol is a precursor for….

A

1) bile salts

2) steroid hormones eg cortisol , aldosterone , testosterone , oestrogen

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6
Q

How is cholesterol transported around the body ?

A

As a cholesterol Ester

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7
Q

How is cholesterol converted into a cholesterol Ester ?

A

It is Esterified with a fatty acid

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8
Q

What are lipoproteins ?

A

They transport water insoluble lipids around the body.

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9
Q

Describe the structure of a lipoprotein

A
  • spherical particles
  • they consist of a surface coat ( shell ) and a hydrophobic core
  • the surface cost contains phospholipid mono layer, small amounts of cholesterol and apoproteins
  • the hydrophobic core contains TAGS , cholesterol esters and fat soluble vitamins
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10
Q

What are the 5 different classes of lipoproteins ?

A

1) chylomicrons
2) VLDL ( very low density lipoprotein)
3) IDL ( intermediate density lipoprotein)
4) LDL ( low density lipoprotein )
5) HDL ( high density lipoprotein)

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11
Q

What makes the 5 different classes of lipoproteins different ?

A

They each have variable content of apoproteins , TAGS, cholesterol and cholesterol esters

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12
Q

The more dense the lipoprotein ( eg high density lipoprotein ) the …. smaller /larger the diameter and the more/less protein there is

A

Smaller the diameter

And a high % of protein

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13
Q

What are the 6 major classes of apoproteins ?

A

A B C D E H

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14
Q

Where are integral apoproteins found ?

A

They pass through the phospholipid bilayer of lipoproteins

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15
Q

Where are peripheral lipoproteins found ?

A

They rest on the top of the lipoprotein

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16
Q

What are the two roles of apoproteins ?

A

1) structural role : they package water insoluble lipids into their soluble form.
2) functional roles : act as co factors for enzymes and ligands for cell surface receptors

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17
Q

What is the role of chylomicrons ?

A
  • they transport dietary lipids in the small intestine into the lymphatic system. They enter the blood stream at the thoracic duct which empties into the left subclavian vein and are then carried to tissues.
  • before entering the Lymphatic system , apoB-48 is added.
  • once in blood ApoC and ApoE is added.
18
Q

What is the role of ApoC once it is added to the chylomicrons when it entered the blood circulation a.

A

ApoC Binds to lipoprotein lipase on adipocytes and muscle.

  • the enzyme hydrolyses the TAGS that were carried by the chylomicrons , releasing fatty acids. Which are either recombined back into TAGS in adipose tissue for storage or are used to generate energy in muscles.
  • when there has been a 20% depletion in TAGS, ApoC dissociates and chylomicrons becomes a chylomicrons remnant which is then taken up by the liver.
19
Q

Where is VLDL made ?

A

In the liver

20
Q

What is the function of VLDL?

A

Transport of TAGS synthesised in the liver to adipose tissue for storage

21
Q

Explain how VLDL transports the TAGS from the liver ?

A
  • apoproteins ApoB100 is added during formation of VLDL.
  • ApoC and ApoE is added from HDL particles in the blood.
  • VLDL binds to lipoprotein lipase on endothelial cells in muscle and adipose and begins to become depleted of TAGS.

-

22
Q

What is the function of IDL?

A

Short lived precursor for LDL.

23
Q

What happens to VLDL as the TAGS content depleted by 30%?

A
  • the particle becomes a short lived IDL particle.
  • IDL particles can also be taken up by the liver or rebind to LPL enzyme to further deplete TAG content.
  • upon depletion of TAG content of IDL by 10% , IDL loses ApoC and ApoE to become an LDL particle.
24
Q

What is the function of LDL?

A

TRANSFER OF CHOLESTEROL FROM THE LIVER TO PERIPHERAL RECEPTORS

  • these peripheral tissues express LDL receptors and take up LDL via receptor mediated endocytosis
25
Q

What is one difference between IDL and LDL ?

A

LDL does not have ApoE or ApoC so are not efficiently Cleared by the liver.

26
Q

Which has a higher cholesterol content - LDL or HDL ?

A

LDL

27
Q

How can LDL lead to the formation of atherosclerotic plaques ?

A
  • half life of LDL is much longer than IDL and VLDL making LDL more susceptible to oxidative damage
  • once oxidised , it is taken up by macrophages that cam transform to foam cells and contribute to the formation of these plaques.
28
Q

Cells that require cholesterol would require what type of receptors ?

A

LDL receptors

29
Q

How does LDL enter cells by receptor mediated endocytosis ?

A

1) ApoB-100 on LDL acts as a ligand for these LDL receptors one plasma membrane.
2) receptor - LDL complex taken into cell by endocytosis into endosomes
3) endosomes fuse with lysosomes for digestion to release cholesterol and fatty acids.

30
Q

What is the function of HDL?

A

TRANSPORT OF EXCESS CHOLESTEROL FROM THE TISSUES TO THE LIVER FOR DISPOSAL AS BILE SALTS AND TO CELLS REQUIRING CHOLESTEROL

31
Q

How is HDL synthesised ?

A

Nascent HDL is synthesised by the liver and intestine

  • HDL particles can also bud off from chylomicrons and VLDL as they are digested by lipoprotein lipase

-

32
Q

How does HDL reverse cholesterol transport ?

A

HDL have the ability to remove cholesterol from cholesterol laden cells and return it to liver

  • this is important for blood vessels as it reduces the likelihood of foam cells and atherosclerotic plaque
  • ABCA1 protein within cell facilitates transfer of cholesterol to HDL. Cholesterol then converted to cholesterol Ester by LCAT.
33
Q

Cells requiring additional cholesterol can utilise what receptor to obtain cholesterol from HDL?

A

Scavenger receptor

34
Q

What protein is used when HDL wants to exchange cholesterol Ester with TAG from VLDL?

A

Cholesterol exchange transfer protein

35
Q

Define hyperlipoproteinaemias

A

After a period of fasting , (12 hours) Raised plasma level by one or more lipoprotein classes

  • caused by over production or under removal
36
Q

What are 3 clinical signs of hypercholesterolaemia?

A

1) Xanthelasma : yellow patches on eyelids
2) tendon Xanthoma : nodules on tendons
3) corneal arcus : obvious white circle around eye. Common in elder people , but if in young it is a clinical sign.

37
Q

How is raised LDL associated with atherosclerosis?

A

1) raised LDL increases likelihood of oxidative damage.
2) LDL becomes oxidised.
3) recognised and engulfed by macrophages
4) lipid laden macrophages called foam cells accumulate in intima of blood vessel walls to forms. Fatty streak
5) fatty streak evolves into atherosclerotic plaque
6) grows in lumen of artery = angina
7) artery ruptures= this triggers acute thrombosis leading to stroke or MI

38
Q

How to treat someone with hyperlipoproteinaemia ?

A

FIRST APPROACH :
1) reduce cholesterol and saturated lipids in diet, increase fibre intake

2) increase exercise , stop smoking

SECOND APPROACH :

1) statins which inhibits HMG coA. Reducing cholesterol synthesis
2) bile salt sequestrants: bind bile salts in GI tract , which forces lover to produce more bile so uses more cholesterol.

39
Q

What is the ideal total cholesterol concentration ?

A

5mmol/L or less

40
Q

What is the ideal LDL cholesterol conc ?

A

3mmol/less

41
Q

Ideal HDL- cholesterol level ?

A

Ideally over 1mmol/L

42
Q

Ideal total cholesterol :HDL-C ratio ?

A

Ratio above 6 considered high risk. The lower the ratio the better.

Metabolism, Endocrinology And Haematology (23 decks)

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