Lipids - Theory Flashcards
Define a lipid
An organic substance (carbon containing) which is poorly soluble in water, but which is soluble in organic solvents or oils
Where do we find lipids?
(3)
Found in cell membranes
Stored in adipocytes - distributed through the body
Fat sores
What are two major fat stores in humans
Subcutaneous
Internal (visceral/retroperitoneal)
What are the two types of internal fat
Visceral
Retroperitoneal
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
Realistically how much internal fat do women have?
3 litres of internal fat for a total of 37 litres
Realistically how much internal fat do men have
5 litres out of 35 litres
Realistically how much internal fat do men have
5 litres out of 35 litres
List the four types of lipids found in plasma
Steroids
Triacylglycerols
Fatty acids
Bioactive lipids
List the three types of steroid lipids found in circulation
Cholesterol
Estrogen
Testosterone
Give five examples of fatty acids found in circulation
Palmitate
Oleata
Linoleate
Linolenate
Docosahaeneoate
List five bioactive lipids found in circulation
Prostaglandins
Eicosanoids
Plasmalogens
Isoprostanes
Leukotrienes
What are triacylglycerols composed of?
Three acyl chains joined to one glycerol molecule by ester linkages
Write about cholesterol
A 27 carbon sterol molecule
Rigid nucleus and flexible 8 carbon side chain
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
What can happen to body fluids after ingestion of a high fat meal?
(2)
They can become opaque
Lipemic serum
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
What are lipoproteins
Complexes of protein and lipids
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
Classify Lipoproteins
(5)
Chylomicron and chylomicron remnant (1000nm/largest)
Very Low Density Lipoprotein
Intermediate Density Lipoprotein
Low Density Lipoprotein
High Density Lipoprotein (10nm)
What is considered the good type of lipoprotein
HDL
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
What are the two systems of lipoprotein metabolism?
Distribution of exogenous lipids
Distrubition of endogenous lipids
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)
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
