Lipid Transport Flashcards
What classes of lipids are normally found in the blood?
- Triacylglycerols
- Fatty acids
- Cholesterol
- Cholesterol esters
- Phospholipids
Why must lipids be transported with protein in the plasma?
As they are insoluble in water
How are lipids carried in the blood?
- 98% are carried as highly specialised non-covalent assemblies called lipoprotein particles
- 2% are carried bound non-covalently to albumin
What is the main class of lipid that travels bound to albumin?
Fatty acids
Where do the fatty acids bound to albumin come from?
They are released from adipose tissue during lipolysis
What are the fatty acids bound to albumin used for?
As a fuel by tissues, e.g. muscle
What is the result of the limited carrying capacity of albumin?
Blood fatty acid levels do not normally exceed 3mM
Why do plasma lipoproteins have a great significance in medicine?
Since disorders in their metabolism are associated with a number of important diseases, e.g. atherosclerosis and coronary artery disease
How do the classes of lipoprotein differ?
- In the lipid being transported
- In the origins of the lipid
- In the destination
What are the protein components of plasma lipoprotein particles?
Apoproteins
What are the apoproteins involved in structurally?
Packaging non-water soluble lipids into soluble form
What allows apoproteins to package non-water soluble lipids into soluble form?
They contain hydrophobic regions that interact with lipid molecules, and hydrophilic regions that interact with water
What are apoproteins involved in functionally?
May be involved in the action of enzymes or recognition of cell surface receptors
What determines the function of a lipoprotein particle
It’s apoprotein composition
Describe the structure of a lipoprotein
Sphreical particles that consist of a surface coat (shell), and a hydrophobic core
What does the surface coat of a lipoprotein particle contain?
- Phospholipids
- Cholestrol
- Apoproteins
What does the hydrophobic core of a lipoprotein contain?
Tryacylglycerol and cholesterol esters
What do lipoproteins require in order to remain stable?
Must keep their spherical shape
What is the maintenance of the spherical shape of lipoproteins dependant on?
The ratio of core to surface lipids, therefore as lipid from the hydrophobic core is removed, the surface coat must be reduced
Are the components of the surface coat of lipoproteins molecules free to transfer?
Many are, but the core components can only be removed by special proteins, e.g. lipases and transfer proteins
What are the types of lipoproteins?
- Chylomicrons
- VLDL
- LDL
- HDL
What is the transport functions of chylomicrons?
Transport dietary triacylglycerols from the intestine to tissues such as adipose tissue
What is the transport function of VLDL?
Transport of triacylglycerols synthesised in the liver to adipose tissue for storage
What is the transport function of LDL?
Transport of cholesterol synthesised in liver to the tissues
What is the transport function of HDL?
Transport of excess tissue cholesterol to the liver for disposal as bile salts
What must be done to dietary lipids to allow their absorption?
They cannot be absorbed directly, and are hydrolysed in the small intestine by the enzyme pancreatic lipase that release fatty acids and glycerol
What happens to the fatty acids produced by pancreatic lipase in the digestion of dietary lipids?
They enter the epithelial cells of the small intestine, where they’re re-esterified back to triacylglycerols using glycerol phosphate from glucose metabolism
What happens to the triacylglycerols produced in the epithelial cells of the small intestines?
They are packaged with other dietary lipids, e.g. cholesterol, fat soluble vitamins into chylomicrons
What happens to the chylomicrons containing the TAGs produced in the epithelial cells of the small intestines?
They are released from the epithelial cells into the blood stream via the lymphatic system, and carried tissues
What tissues are chylomicrons carried to?
Those that express extracellular enzyme lipoprotein lipase, e.g. adipose
What is the action of lipoprotein lipase?
It hydrolyses the triacylglycerols to release fatty acids that enter the cell
What happens to the fatty acids entering the cell after being hydrolysed by LPL?
They are converted to triacylglycerols for storage
What is lipoprotein lipase responsible for?
Removing the core triacylglycerols from lipoproteins such as chylomicrons and VLDLs
Where is lipoprotein lipase found?
It’s attached to the inner surface of capillaries in tissues such as adipose tissue and muscle
What molecule increases the synthesis of lipoprotein lipase?
Insulin
What is the action of lipoprotein lipase?
It hydrolyses triacylglycerols in lipoprotein particles, releasing fatty acids and glycerols
What happens to the products of triacylglycerol hydrolysis?
- The tissues take up fatty acids
- The glycerols go to the liver
What restores the stability of lipoproteins?
Lecithin:cholesterol acyltransferase (LCAT)
How does LCAT restore the stability of lipoproteins?
It converts the surface lipid to core lipid
What does LCAT convert cholesterol to?
Cholesterol ester
How does LCAT convert cholesterol to cholesterol ester?
Using fatty acid derived from lecithin (phophatidylcholine)
What does deficiency of LCAT result in?
Unstable lipoproteins of abnormal structure, therefore generally failure of lipid transport. Lipid deposits occur in many tissues, and atherosclerosis is a serious problem
How do tissues obbtain the cholesterol they need?
From LDL, by the process of receptor-mediated endolytosis
What happens in the receptor-mediated endocytosis of LDL particles?
LDL particles are taken up by the cell, and the cholesterol is released inside the cell
What cells are able to synthesise cholesterol from acetyl-CoA?
All apart from erythrocytes
Can cells satisfy their cholesterol requirements by biosynthesis?
Yes
What cells prefer the uptake of pre-formed cholesterol circulating in plasma lipoproteins, compared to biosynthesis?
All
How do cells obtain preformed cholesterol?
- Cells requiring cholesterol synthesise LDL receptors that are exposed to the cell surface
- The LDL receptor with its bound LDL is then endocytosed by the cell, and subjected to lysosomal digestion
- Cholesterol esters are converted to free cholesterol that is released within the cell
- The cholesterol can be stored as cholesterol esters, or used by the cell
What effect does the endocytosis of pre-formed cholesterol have on cholesterol biosynthesis?
It inhibits it, and reduces the synthesis and exposure of LDL receptors. This prevents the cell from accumulating too much cholesterol
What are the types of hyperlipoproteinaemias?
I-V
What is type I hyperlipoproteinaemia?
Chylomicrons are found in the fasting plasma
Is type I hyperlipoproteinaemia linked to coronary artery disease?
No
What is type I hyperlipoproteinaemia caused by?
Defective lipoprotein lipase
What is type IIa hyperlipoproteinaemia?
Raised LDL
Is type IIa hyperlipoproteinaemia associated with coronary artery disease?
Yes, may be severe
What is type IIa hyperlipoproteinaemia caused by?
Defective LDL receptor
What is type IIb hyperlipoproteinaemia?
Raised LDL and VLDL
Is type IIa hyperlipoproteinaemia associated with coronary artery disease?
Yes
What is the defect in type IIa hyperlipoproteinaemia?
Unknown
What is type III hyperlipoproteinaemia?
Raised IDL and chylomicron remnants
What is type III hyperlipoproteinaemia associated with?
Coronary artery disease
Is type III hyperlipoproteinaemia associated with coronary artery disease?
Yes
What is the defect in type III hyperlipoproteinaemia?
Defective apoprotein E
What is type IV hyperlipoproteinaemia?
Raised VLDL
Is type IV hyperlipoproteinaemia associated with coronary artery disease?
Yes
What is the defect in type IV hyperlipoproteinaemia?
Unknown
What is type V hyperlipoproteinaemia?
Raised chylomicrons and VLDL in fasting plasma
Is type V hyperlipoproteinaemia associated with coronary artery disease?
Yes
What is the defect in type V hyperlipoproteinaemia?
Unknown
What kind of hyperlipoproteinaemia is familial hypercholesterolaemia?
Type IIa
What is familal hypercholesterolaemia?
A condition in which there be absense (when homozygous trait) or deficiency (heterozygous) of functional LDL receptors
What is familial hypercholesterolaemia characterised by?
Elevated levels of LDL and cholesterol in the plasma
How does the course of the disease differ in homozygotes and heterozygotes?
Homozygotes develop extensive atherosclerosis early in life, and heterozygotes develop the condition in later life
How can hyperlipoproteinaemias be treated?
- Diet and lifestyle modifications
- Drug therapy
What diet and lifestyle changes are made in hyperlipoproteinaemias?
- Increase exercise
- Aiming to reduce/eliminate cholesterol from the diet
- Reduce the intake of triacylglycerols, especially those with saturated fatty acids
Are diet and lifestyle modifications effective in all patients with hyperlipoproteinaemias?
No, in some it will have little effect
What drug therapies are used in the treatment of hyperlipoproteinaemias?
- Statins
- Bile salt sequesterants
How do statins reduce plasma cholesterol?
They reduce the synthesis of cholesterol in tissues
Give an example of a bile salt sequestrant
Cholestyramine
How do bile salt sequesterants lower cholesterol?
By increasing its disposal from the body, by binding to bile salts in the GI tract, preventing them from being reabsorbed into the hepatic-portal circulation, and promoting their loss in faeces
