Lipid transport Flashcards
What three interlinked systems are lipid transported by?
The exogenous pathway transports lipids from the gut to the liver
The endogenous pathway transports lipids synthesised by the liver to non-hepatic tissue including adipocytes
The third pathway takes lipids from the circulation and from non-hepatic tissue back to the liver
What are the different fats and lipids in circulation?
Triglycerides (45%) Phospholipids (35%) Cholesterol esters and cholesterol (15%) Free fatty acids (5%) % in human plasma varies greatly with nutritional state All are insoluble in water
What are free fatty acids?
Formed from triglycerides stored in adipose tissue
Circulates bound to protein as Na+ salt particularly albumin as unbound FA would act as a detergent
Saturation occurs at about 2mM FA molecules
FA enter cells by simple diffusion
Intracellular concentration FFA kept low
What are lipoproteins?
Fatty acids are transported throughout the body as lipoproteins
Carried in the blood as plasma lipoproteins
There are five types of lipoproteins:
Chylomicrons
Low density lipoproteins (LDL)
Very low density lipoproteins (VLDL)
High density lipoproteins (HDL)
Intermediate density lipoproteins (IDL)
The composition of a particular lipoprotein is characterised by the apolipoprotein component(s)
What are apolipoproteins/apoproteins?
The protein that is associated with the lipoprotein
The composition of a particular lipoprotein is characterised by the apolipoprotein component(s)
Some of these apolipoproteins can be exchanged between lipoproteins
What are the functions of apolipoproteins?
Structural To solubilise lipids Act as enzymes or enzyme cofactors: Apo CII for lipoprotein lipase Apo AI for lecithin- cholesterol acyltransferase Tissue targeting: Apo B100 and Apo E to the LDL receptor Apo E binds to the HDL receptor
What happens to the dietary lipids in the body?
Dietary lipids enter the gut as primarily triglycerides which undergo enzymatic breakdown using lipases to form FA and monoacylglycerol which then enter the cell and reform triglycerides and these along with other lipids will form a chylomicron which also contain the protein Apo B48
The nascent chylomicron will be secreted by a process of reverse-pinocytosis into the lymphatic system then start to circulate the body
Following synthesis and release into the circulation, the nascent chylomicrons will interact with HDL where it will pick up a no. of apolipoproteins including Apo E and Apo CII
Summary:
Low density due to high TG
B48 added in the SER
Secreted by reverse pinocytosis in to the lymphatics
Apo C2, C3 and E transferred from HDLs
What happens to the chylomicrons during circulation?
As the chylomicrons circulates it will then undergo enzymatic degradation by interaction with an enzyme called lipoprotein lipase, expressed on tissues which predominantly metabolise lipids such as muscle, adipocytes and mammary glands
What happens to LPL in circulation?
Km of LPL isoform in adipocytes is greater than muscle
This means that the muscle will take up the FA in preference to the adipocytes
The LPL interacts with the LP via the Apo CII, acting as inactivation of the lipase
LPL on adipocytes is stimulated by insulin
What are the different types of hyperlipidaemia?
Type 1: deficiency in lipoprotein lipase or Apo C2- characterised by high plasma triglyceride
Type 2: Characterised by high LDL- most are caused by a genetic defect in the synthesis, processing or function of the LDL receptor
Type 4: Most common form results in raised VLDL concentration often due to obesity or alcohol abuse
What are some additional facts about chylomicrons?
Reflects meal composition
Low density due to high TG
Also contain fat soluble vitamins- Vit A and E
Life time in the circulation of 1h (TG 5mins)
Remnants removed by the liver with the involvement of Apo E
What are VLDLs?
Very low density lipoproteins
Synthesised by the liver when dietary intake of carbohydrates exceeds immediate needs
Triglycerides formed are packaged with FFA, phospholipids and cholesterol eaters and Apo B100 to form nascent VLDL
Formation stimulated by insulin and inhibited by glucagon
Nascent VLDLs receive Apo E and Apo CII from HDL
Remnants removed by the liver by Apo E (TG 15-60mins)
What are LDLs?
Low density lipoproteins
Are the major carrier of cholesterol
Metabolised slowly- 3 days
Carry cholesterol to the periphery and regulate de novo synthesis
Contain 1 Apo B100 which can bind to a specific receptor on hepatocytes
What are HDLs?
High density lipoproteins
Can be created in 3 ways:
As nascent particles by the liver and intestine
Budding of apolipoproteins from chylomicrons
From free Apo AI
Nascent HDL acquire cholesterol and phospholipids from endothelial cells
Most important function reverse cholesterol transport
This transfer does not require enzymes
HDL possess lecithin cholesterol acyltransferase LCAT which catalyses cholesterol esterification preventing it from returning to the cell
Particularly important in vascular cells- prevents foam cell formation
Cholesterol rich HDL can either deliver it to the liver or exchange it with other particles including VLDL and VLDL remnants
How are lipoproteins used diagnostically?
HDL/LDL Used diagnostically HDL is the 'good' cholesterol LDL is the 'bad' cholesterol HDL/LDL ration is used to assess susceptibility to heart disease Normal individuals have a ratio of 3.5
