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a'M' of MEH COPY (SC) > Lecture 4- Transport of lipids > Flashcards

Lecture 4- Transport of lipids Flashcards

1
Q

lipids are a diverse group of compounds

A

TAG

Fatty acids

Cholesterol

Phospholipids

Vitamine A, D, E, K (always do eat kitkats)

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2
Q

features of lipids

A
  • Hydrophophic molecules (insoluble in water) –> problem for transport in blood
  • Therefore transported in blood bound carrier
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3
Q

2% of lipids (fatty acids) are carried bound to

A

albumin –> limited capacity

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4
Q

98% of lipids are carried as

A

lipoprotein particles consisitng of:

  • phospholipid
  • cholesterol
  • cholesterol esters
  • proteins
  • TAG
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5
Q

Typical plasma lipid conc ranges

A
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6
Q

structure of phospholipids

A
  • Polar (hydrophilic) head group
    • Head group
    • E.g. choline (classified according to polar head group (phosphatidylcholine)
    • Phosphate and glycerol
  • Non-polar (hydrophobic) tail
    • Fatty acids
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7
Q

unsatruates fatty acids tail (CIs bond) allowa

A

fluidity

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8
Q

what are micelles

A

single layer of phopsholipids- spherical

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9
Q

Liposomes

A

spherical phospholipid bilayer

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10
Q

some cholesterol is from the ………., most is synthesised in the …….

A

Some cholesterol from the diet, most synthesised in liver

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11
Q

Cholesterol role in the body

A
  • Essential components of membrane (modulates fluidity)
  • Precursor of steroid hormones
    • Cortisol
    • Oestrogen
    • Aldosterone
    • Testosterone
  • Precursors of bile acids
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12
Q

cholesterol is transported around the body

A

as cholesterol ester (cholesterol with fatty acid group added)

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13
Q

cholesterol ester

A

cholesterol with fatty acid attached

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14
Q

lipoproteins

A

Micelles consisting of a single phospholipid sphere

  • Transport lipid around the body
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15
Q

lipoprotein cargo

A
  • TAG
  • Cholesterol ester
  • Fat soluble vitamins
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16
Q

structure of lipoproteins

A

Micelles

  • Have integral or peripheral apolipoproteins in the phospholipid membrane- which define what sort of lipoprotein it is
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17
Q

how many classes of lipoproteins

A

5 distinct classes

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18
Q

name the 5 distinct classes of lipoprotein

A
  1. chylomicrons
  2. VLDL
  3. IDL
  4. LDL
  5. HDL
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19
Q

chylomicrons

A

transport dietary fat- TAG

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20
Q

VLDL

A

very low density lipids

fat made in the liver and exported in very low density lipoproteins

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21
Q

IDL

A

intermediate density lipoprotein

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22
Q

LDL

A

density lipoprotein

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23
Q

HDL

A

high density lipoprotein

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24
Q

diameter of liporptoeins

A

the less dense e.g. chylomicrons, the larger the lipoprotein

HDL most dense and smallest

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25
Q

particle diamter relationship to density

A

Particle diameter inversely proportional to density

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26
Q

Levels of lipoproteins in blood are of significant clinical importance

A

Density obtained by flotation ultracentrifugation

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27
Q

which lipoproteins are the main carriers of fat

A

chylomicrons and VLDL

28
Q

chylomicrons are normally only present in the blood

A

4-6h after a meal

29
Q

which lipoproteins are the main carriers of cholesterol esters

A

IDL

LDL

HDL

30
Q

Apolpoproteins

A
  • Each class of lipoprotein particle has a particular complement of associated proteins
  • Six major classes (ABCDEH)
    • apoB (VLDL, IDL, LDL) and apoA1 (HDL) important
31
Q

apoB

A

VLDL, IDL, LDL

32
Q

apoA1

A

HDL

33
Q
A
34
Q

where are apoloproteins found

A

Can be integral- passing through phospholipid bilayer

Peripheral - resting on top

35
Q

roles of apoloproteins: structural

A

packaging water insoluble lipid

36
Q

role of apoloproteins: functional

A
  1. Co-factor for enzymes
  2. Ligands for cell surface receptors
37
Q

transport function of chylomicrons (simple)

A

transport of dietary TAG from the intestine to tissues such as adipose

38
Q

transport function of VLDL (simple)

A

transport of TAG synthesised in liver to adipose tissue for storage

39
Q

transport function of IDL (simple)

A

short-liver precursor of LDL

transport of cholesterol synthesied in the liver to the tissues

40
Q

transport function of LDL (simple)

A

transport of cholesterol synthesised in liver to tissue

41
Q
A
42
Q

transport function of HDL (simple)

A

transport of excess choelsterol from cells to liver for disposal as bile salt and to cells requiring additional cholesterol

43
Q

chylomicrons metabolism

A
  1. Loaded in the small intestine and apoB-48 added before entering lymphatic system
  2. Travel to the thoracic duct which empties into left subclavian vein and acquire 2 new apoproteins (apoC and apoE) once in blood
  3. ApoC binds lipoprotein lipase (LPL) on capillary wall of adipocytes and muscle
    • Release of fatty acids into muscle and adipocytes depletes chylomicron of fat content
  4. When TAG is reduced to 20%, apoC dissociate and chylomicron becomes a chylomicron remnant
  5. Chylomicron remnants returns to the liver
  6. LDL receptor on hepatocytes bind apoE and chylomicron remnant taken up by receptor mediated endocytosis
  7. Lysosomal degradation of remaining contents for use in metabolism
44
Q

VLDL metabolism

A

VLDL made in liver for purpose of transporting TAG to other tissues

  1. Apolipoprotein apob100 added during formation and apoC and apoE added from HDL particles in blood
  2. VLDL binds to lipoprotein lipase (LPL) on endothelial cells in muscle and adipose and becomes depleted of TAG
  3. In muscle…. Released fatty acids taken up and used for energy production
  4. In adipose…. Fatty acids are used for the re-synthesis of TAG and stored as fat
45
Q

IDL and LDL metabolism

A

VLDL –> IDL –> LDL

  1. As triacylglycerol content of VLDL particles drops some, VLDL particles dissociates from the LPL enzyme complex and return to liver
  2. If VLDL content depletes to ~30%, the particle becomes a short-lived IDL particle.
  3. IDL particles can also be taken up by liver or rebind to LPL enzyme to further deplete in TAG content
  4. Upon depletion to ~ 10%, IDL loses apoC & apoE and becomes an LDL particle (high cholesterol content)
46
Q

function of LDL

A
  1. Provides cholesterol from liver to peripheral tissue
  2. Peripheral cells express LDL receptors and take up LDL via process of receptor mediated endocytosis
47
Q

importantly LDL does not have

A

apoC or apoE

not efficiently cleared by the liver (liver LDL- receptor has a high affinity of apoE)

48
Q

LDL clinical relevance

A

Raised serum LDL associated with atherosclerosis

49
Q

why is LDL associated with atherosclerosis

A

LDL has a much longe half life than VLDL or IDL

50
Q

Why is raised serum LDL associated with atherosclerosis…

A
  1. LDL has much longer half-life than VLDL or IDL making LDL more susceptible to oxidative damage
  2. Oxidative LDL taken up by macrophages that can transform to foam cell and contribute to formation of atherosclerotic plaques
51
Q

formation of atheromas due to LDL

A
  1. Oxidised LDL (longer half life more vulnerable to ROS)
  2. Recognised and engulfed by macrophages
  3. Lipid laden macrophages à foam cells accumulate in intima of blood vessel walls to form a fatty streak
  4. Fatty streak evolves into atherosclerotic plaque
  5. Growth and encroaches on lumen of the artery
52
Q

Growth and encroaches on lumen of the artery by the atheroma can cause

A
  1. Angina (narrowing of arteries) or..
  2. Rupture
53
Q

rupture of plaque triggers

A
  • acute thrombosis (clot) by activating platelets and clotting cascade
    • Stroke
    • Myocardial infarction
54
Q

plaque formaiton in diagram

A
55
Q

Clinical signs of hypercholesterolaemia

A
  • Xanthelasma
  • Tendon xanthoma
  • Corneal arcus
56
Q

Xanthelasma

A

– yellow patches on eyelids

57
Q

tendon xanthoma

A

nodules on tendon

58
Q

corneal arcus

A

obvious white circle around eye (common in older people)

59
Q

VLDL, IDL and LDL metabolism

A
60
Q

outline how cells requiring cholesterol receive it from LDLs

A
  1. Cells requiring cholesterol express LDL receptors on plasma membrane
  2. apoB-100 on LDL acts as a ligand for these receptors
  3. Receptor/LDL complex taken into cell by endocytosis into endosomes
  4. fuse with lysosomes for digestion to release cholesterol and fatty acids
  5. LDL-R expression controlled by cholesterol conc in the cell
61
Q

HDL synthesis

A
  • Synthesis- nascent HDL synthesised by liver and intestine (low TAG levels)
  • HDL particles can also but off from chylomicrons and VLDL as they are digested by LPL
  • Free apoA-I can also acquire cholesterol and phospholipid from other lipoproteins and cell membranes to form nascent-like HDL
62
Q

Maturation of HDL

A

Nascent HDL accumulates phospholipids and cholesterol from cells lining blood vessels

Hollow core progressively fills and particle takes more globular shape

Transfer of lipids to HDL does not require enzyme activity

63
Q

HDL responsible for

A

reverse cholesterol transport

64
Q

Reverse cholesterol transport

A
  1. HDL have ability to remove cholesterol from cholesterol-laden cells and return it to the liver
  2. Important process for blood vessels as it reduced likelihood of foam cells and atherosclerotic plaque formation
  3. ABCA1 protein within cell facilitates transfer of cholesterol to HDL
  4. Cholesterol converted to cholesterol ester by lCAT
65
Q

fate of mature HDL

A
  • Taken up by liver via specific receptors
  • Cells requiring additional cholesterol e.g. for steroid hormone synthesis can also utile scavenger receptors (SR-B1) to obtain cholesterol from HDL
  • HDL can also exchange cholesterol ester for TAG and VLDL via action of cholesterol exchange transfer protein (CETP)

a'M' of MEH COPY (SC) (11 decks)

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