Lipids - Theory Flashcards by Aífe Hayden

Define a lipid

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

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Where do we find lipids?
(3)

Found in cell membranes

Stored in adipocytes - distributed through the body

Fat sores

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What are two major fat stores in humans

Subcutaneous
Internal (visceral/retroperitoneal)

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What are the two types of internal fat

Visceral
Retroperitoneal

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Comment on the recommended ratio between internal and external lipid

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

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Realistically how much internal fat do women have?

3 litres of internal fat for a total of 37 litres

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Realistically how much internal fat do men have

5 litres out of 35 litres

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Realistically how much internal fat do men have

5 litres out of 35 litres

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List the four types of lipids found in plasma

Steroids

Triacylglycerols

Fatty acids

Bioactive lipids

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List the three types of steroid lipids found in circulation

Cholesterol
Estrogen
Testosterone

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Give five examples of fatty acids found in circulation

Palmitate
Oleata
Linoleate
Linolenate
Docosahaeneoate

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List five bioactive lipids found in circulation

Prostaglandins
Eicosanoids
Plasmalogens
Isoprostanes
Leukotrienes

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What are triacylglycerols composed of?

Three acyl chains joined to one glycerol molecule by ester linkages

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Write about cholesterol

A 27 carbon sterol molecule

Rigid nucleus and flexible 8 carbon side chain

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Describe the absorption of lipids
(4)

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

They can become opaque

Lipemic serum

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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?

Through the use of lipoproteins

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

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What are lipoproteins

Complexes of protein and lipids

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What are lipoproteins composed of
(3)

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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Classify Lipoproteins
(5)

Chylomicron and chylomicron remnant (1000nm/largest)

Very Low Density Lipoprotein

Intermediate Density Lipoprotein

Low Density Lipoprotein

High Density Lipoprotein (10nm)

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What is considered the good type of lipoprotein

HDL

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Why do lipoproteins exist
(2)

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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What are the two systems of lipoprotein metabolism?

Distribution of exogenous lipids
Distrubition of endogenous lipids

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What is the common structure in all lipoproteins?

Outer monolayer of amphiphatic lipids

Inner cargo of highly hydrophobic lipids e.g. TAGs

Integral and peripheral proteins (apolipoproteins)

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What are amphiphatic lipids?

Lipids that are hydrophilic at one end and hydrophobic at the other end e.g. phospholipids or some cholesterols

How are lipoproteins calssified

According to density and electrophoretic mobility

What is low density lipoprotein composed of

Unesterified cholesterol Phospholipid Cholesteryl ester Apoprotein B-100

Which lipoprotein contains the most triglyceride

Chylomicrons

Which liporotein contains the most cholesterol

HDL

Which lipoprotein contains the least cholesterol

VLDL

Which lipoprotein contains the most protein

HDL

What is the primary source of chylomicrons

Gut

What is the principle lipid in chylomicrons

TAGs

What is the primary source of VLDL?

Liver

What is the principle lipid in VLDL

TAG

What is the primary source of LDL

From VLDL

What is the principle lipid in LDL

Cholesterol

What is the primary source of HDL

Many tissues

What is the principle lipids in HDL

P-lipids and cholesterol

Give five examples of apolipoproteins

ApoA1 ApoB48 ApoB100 ApoCII Apo E

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

Made in many tissues Activates LCAT Carries HDL

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

Carries chylomicrons Made by enterocytes Its a LRP-receptor ligand

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

Carries VLDL and LDL Made in the liver An LDL-receptor ligand

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

Carries VLDL and HDL Made in the liver Activates lipoprotein lipase

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

Carries VLDL and IDL Made by many tissues, especially the liver Its an LDL-receptor ligand

What is LCAT (2)

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

What is an LRP-receptor

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

What is an LDL-receptor?

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

What is lipoprotein lipase

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

What is the exogenous pathway of lipoprotein metabolism

Absorption and distribution of external lipids (chylomicrons)

What is the endogenous pathway of lipoprotein metabolism?

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

Where are chylomicrons formed and how? (3)

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

What happens after enterocytes form chylomicrons

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

What happens to chylomicrons in blood

Chylomicrons donate ApoA1 to HDL and pick up ApoCII and ApoE

What is ApoCII

An activator of lipoprotein lipase

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

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

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

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

What happens to chylomicron remnants (2)

They are taken up by the liver via receptor mediated endocytosis: LDLR or LRP-1 (LDL receptor related protein 1)

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

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

What apolipoproteins does VLDL contain? (3)

ApoB100 ApoE ApoCII

What does VLDL do?

Delivers TAG to tissues

What does VLDL rely on?

The activity of lipoprotein lipase

Describe the relationship between TAG and cholesterol

As TAG are delivered the relative cholesterol content increases

What happens when VLDL delivers TAGs?

A VLDL remnant particle is produced

What is a VLDL remnant particle also caleld

Intermediate density lipoprotein

What percentage of the TAGs from VLDL does IDL contain

10% from parent VLDL

What does IDL lack and what does this mean

IDL lacks ApoCII It cannot activate lipoprotein lipase

What happens to IDL

It can be taken up by the liver

How is IDL taken up by the liver

This is mediated by ApoE binding to LDLR or LRP1

What happens to IDL in the liver

It can be modified by hepatic lipase It eventually becomes low density lipoproteins

What are the properties of LDL

Rich in cholesterol Contain ApoB100 Can be taken up by cells expressing LDLR via receptor mediated endocytosis

What happens to LDLR after receptor mediated endocytosis of LDL

The LDLR is recycled to the cell surface

What is forward lipid transport

Movement of lipids from the liver to the periphery

What is reverse cholesterol transport

Cholesterol is transported from the periphery back to the liver

What is the key mediator of forward and reverse transport?

HDL

What initiates endogenous lipid metabolism

Lipid poor ApoA1 synthesis in the periphery ApoA1 formed is discoidal in shape and very protein rich

What is formed when ApoA1 is loaded with cholesterol?

Nascent HDL is formed This is also known as B-HDL

What is nascent HDL also known as

B-HDL

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

LCAT Lecithin:cholesterol acyltransferase

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

Via the HDL receptor SRB1