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2.2 Clinical Chemistry > Lipids - Theory > Flashcards

Lipids - Theory Flashcards

1
Q

Define a lipid

A

An organic substance (carbon containing) which is poorly soluble in water, but which is soluble in organic solvents or oils

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2
Q

Where do we find lipids?
(3)

A

Found in cell membranes

Stored in adipocytes - distributed through the body

Fat sores

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3
Q

What are two major fat stores in humans

A

Subcutaneous
Internal (visceral/retroperitoneal)

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4
Q

What are the two types of internal fat

A

Visceral
Retroperitoneal

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5
Q

Comment on the recommended ratio between internal and external lipid

A

Young healthy person should have 2 litres of internal fat out of a total 20 litres

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6
Q

Realistically how much internal fat do women have?

A

3 litres of internal fat for a total of 37 litres

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7
Q

Realistically how much internal fat do men have

A

5 litres out of 35 litres

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8
Q

Realistically how much internal fat do men have

A

5 litres out of 35 litres

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9
Q

List the four types of lipids found in plasma

A

Steroids

Triacylglycerols

Fatty acids

Bioactive lipids

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10
Q

List the three types of steroid lipids found in circulation

A

Cholesterol
Estrogen
Testosterone

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11
Q

Give five examples of fatty acids found in circulation

A

Palmitate
Oleata
Linoleate
Linolenate
Docosahaeneoate

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12
Q

List five bioactive lipids found in circulation

A

Prostaglandins
Eicosanoids
Plasmalogens
Isoprostanes
Leukotrienes

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13
Q

What are triacylglycerols composed of?

A

Three acyl chains joined to one glycerol molecule by ester linkages

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14
Q

Write about cholesterol

A

A 27 carbon sterol molecule

Rigid nucleus and flexible 8 carbon side chain

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15
Q

Describe the absorption of lipids
(4)

A

Lipids enter the enterocyte at the lumenal side

Lipids are processed within the enterocyte and loaded onto transport particles called chylomicrons

These are secreted from the basolateral side of enterocyte into the lymph

These pass through the lymph system and enter the systemic circulation at the thoracic duct

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16
Q

What can happen to body fluids after ingestion of a high fat meal?
(2)

A

They can become opaque

Lipemic serum

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17
Q

Lipids are hydrophobic and cannot dissolve in the blood plasma, we need some way to get them through the blood, how do we do this?

A

Through the use of lipoproteins

These act as taxi caps - transporters to carry lipids through circulation

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18
Q

What are lipoproteins

A

Complexes of protein and lipids

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19
Q

What are lipoproteins composed of
(3)

A

Cargo lipids - sequestered in the hydrophobic core

Amphiphatic phospholipids - these form a layer around the lipid cargo and allow the particle to dissolve in circulation

Apolipoproteins - these define the properties of the lipoprotein

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20
Q

Classify Lipoproteins
(5)

A

Chylomicron and chylomicron remnant (1000nm/largest)

Very Low Density Lipoprotein

Intermediate Density Lipoprotein

Low Density Lipoprotein

High Density Lipoprotein (10nm)

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21
Q

What is considered the good type of lipoprotein

A

HDL

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22
Q

Why do lipoproteins exist
(2)

A

They act as a biochemical mechanism for distribution of hydrophobic cargo in an aqueous environment

Transport of cholesterol, TAGs, Fat-soluble vitamins, xenobiotics, phytochemicals, pharmaceuticals

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23
Q

What are the two systems of lipoprotein metabolism?

A

Distribution of exogenous lipids
Distrubition of endogenous lipids

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24
Q

What is the common structure in all lipoproteins?

A

Outer monolayer of amphiphatic lipids

Inner cargo of highly hydrophobic lipids e.g. TAGs

Integral and peripheral proteins (apolipoproteins)

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25
Q

What are amphiphatic lipids?

A

Lipids that are hydrophilic at one end and hydrophobic at the other end

e.g. phospholipids or some cholesterols

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26
Q

How are lipoproteins calssified

A

According to density and electrophoretic mobility

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27
Q

What is low density lipoprotein composed of

A

Unesterified cholesterol

Phospholipid

Cholesteryl ester

Apoprotein B-100

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28
Q

Which lipoprotein contains the most triglyceride

A

Chylomicrons

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29
Q

Which liporotein contains the most cholesterol

A

HDL

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30
Q

Which lipoprotein contains the least cholesterol

A

VLDL

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31
Q

Which lipoprotein contains the most protein

A

HDL

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32
Q

What is the primary source of chylomicrons

A

Gut

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33
Q

What is the principle lipid in chylomicrons

A

TAGs

34
Q

What is the primary source of VLDL?

A

Liver

35
Q

What is the principle lipid in VLDL

A

TAG

36
Q

What is the primary source of LDL

A

From VLDL

37
Q

What is the principle lipid in LDL

A

Cholesterol

38
Q

What is the primary source of HDL

A

Many tissues

39
Q

What is the principle lipids in HDL

A

P-lipids and cholesterol

40
Q

Give five examples of apolipoproteins

A

ApoA1
ApoB48
ApoB100
ApoCII
Apo E

41
Q

What is the origin, function and what is carried by ApoA1

A

Made in many tissues

Activates LCAT

Carries HDL

42
Q

What is the origin, function and what is carried by ApoB48

A

Carries chylomicrons

Made by enterocytes

Its a LRP-receptor ligand

43
Q

What is the origin, function and what is carried by ApoB100

A

Carries VLDL and LDL

Made in the liver

An LDL-receptor ligand

44
Q

What is the origin, function and what is carried by ApoCII?

A

Carries VLDL and HDL

Made in the liver

Activates lipoprotein lipase

45
Q

What is the origin, function and what is carried by ApoE

A

Carries VLDL and IDL

Made by many tissues, especially the liver

Its an LDL-receptor ligand

46
Q

What is LCAT
(2)

A

Lecithin–cholesterol acyltransferase

An enzyme that converts free cholesterol into cholesteryl ester (a more hydrophobic form of cholesterol), which is then sequestered into the core of a lipoprotein particle

47
Q

What is an LRP-receptor

A

LDL receptor-related protein

A multifunctional endocytotic receptor responsible for binding and internalising a broad spectrum of structurally unrelated ligands including lipoproteins

48
Q

What is an LDL-receptor?

A

An oligomeric surface glycoprotein that plays a pivotal role in LDL clearance and cholesterol homeostasis.

49
Q

What is lipoprotein lipase

A

A water soluble enzyme that hydrolyzes triglycerides in lipoproteins, such as those found in chylomicrons and very low density lipoproteins.

50
Q

What is the exogenous pathway of lipoprotein metabolism

A

Absorption and distribution of external lipids (chylomicrons)

51
Q

What is the endogenous pathway of lipoprotein metabolism?

A

Redistribution of internal lipids (forward transport - away from liver; VLDL and LDL, reverse transport - back to liver; HDL)

52
Q

Where are chylomicrons formed and how?
(3)

A

In the enterocyte ingested lipids are packaged into chylomicrons

  • TAGs are converted to MAG (monoacyl…) and 2 fatty acids for absorption and are reformed inside the enterocyte

Chylomicron contain ApoB48 and ApoA1

53
Q

What happens after enterocytes form chylomicrons

A

Chylomicrons are secreted into the lymphatic system and return to the blood at the thoracic duct

54
Q

What happens to chylomicrons in blood

A

Chylomicrons donate ApoA1 to HDL and pick up ApoCII and ApoE

55
Q

What is ApoCII

A

An activator of lipoprotein lipase

56
Q

What does the activation of lipoprotein lipase do?
(3)

A

Lipoprotein lipase at the endothelium hydrolyses the TAG (of chylomicrons) to MAG and 2FA

The MAG diffuse into nearby cells

FA can be picked up by albumin and transported around the body; albumin is the principle transporter of free FA

57
Q

What happens after the activity of lipoprotein lipase on chylomicrons
(4)

A

The chylomicrons shrink as they have lost their TAG cargo

ApoCII and ApoA1 are delivered to HDL particles

Chylomicron remnants are formed

The relative enrichment with cholesterol is increased

58
Q

What happens to chylomicron remnants
(2)

A

They are taken up by the liver via receptor mediated endocytosis:

LDLR or LRP-1 (LDL receptor related protein 1)

59
Q

When is endogenous lipid metabolism required and how does it occurs
(3)

A

The liver synthesises TAG when excess carbohydrates are present (carbs-> acety-CoA -> fatty acyl chain)

But the liver cant store high levels of fat so it is secreted

VLDL is secreted to transport lipids from liver to the periphery -> these contain mainly TAG and some cholesterol

60
Q

What apolipoproteins does VLDL contain?
(3)

A

ApoB100
ApoE
ApoCII

61
Q

What does VLDL do?

A

Delivers TAG to tissues

62
Q

What does VLDL rely on?

A

The activity of lipoprotein lipase

63
Q

Describe the relationship between TAG and cholesterol

A

As TAG are delivered the relative cholesterol content increases

64
Q

What happens when VLDL delivers TAGs?

A

A VLDL remnant particle is produced

65
Q

What is a VLDL remnant particle also caleld

A

Intermediate density lipoprotein

66
Q

What percentage of the TAGs from VLDL does IDL contain

A

10% from parent VLDL

67
Q

What does IDL lack and what does this mean

A

IDL lacks ApoCII

It cannot activate lipoprotein lipase

68
Q

What happens to IDL

A

It can be taken up by the liver

69
Q

How is IDL taken up by the liver

A

This is mediated by ApoE binding to LDLR or LRP1

70
Q

What happens to IDL in the liver

A

It can be modified by hepatic lipase

It eventually becomes low density lipoproteins

71
Q

What are the properties of LDL

A

Rich in cholesterol

Contain ApoB100

Can be taken up by cells expressing LDLR via receptor mediated endocytosis

72
Q

What happens to LDLR after receptor mediated endocytosis of LDL

A

The LDLR is recycled to the cell surface

73
Q

What is forward lipid transport

A

Movement of lipids from the liver to the periphery

74
Q

What is reverse cholesterol transport

A

Cholesterol is transported from the periphery back to the liver

75
Q

What is the key mediator of forward and reverse transport?

A

HDL

76
Q

What initiates endogenous lipid metabolism

A

Lipid poor ApoA1 synthesis in the periphery

ApoA1 formed is discoidal in shape and very protein rich

77
Q

What is formed when ApoA1 is loaded with cholesterol?

A

Nascent HDL is formed

This is also known as B-HDL

78
Q

What is nascent HDL also known as

A

B-HDL

79
Q

What needs to act on B-HDL to form a-HDL

A

LCAT

Lecithin:cholesterol acyltransferase

80
Q

How is cholesterol content of a-HDL delivered to liver?

A

Via the HDL receptor SRB1

2.2 Clinical Chemistry (28 decks)

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