Lipid Transport Flashcards
Name the major groups ‘lipids’ include
Triacylglycerol, fatty acids, cholesterol, phospholipids, vit A D E K
Outline the key characteristics of lipids
Hydrophobic,
~2% transported by albumin,
~98% carried as lipoproteins
What do lipoprotein particles consist of?
Phospholipids, cholesterol, cholesterol esters, proteins, TAG
What is cholesterol?
Essential component of membranes,
synthesised in liver,
precursor to steroids and bile acids,
transported as cholesterol ester
What are the 5 classes of lipoproteins?
Chylomicrons,
VLDL (very low density lipoproteins),
IDL (intermediate density lipoproteins),
LDL (low density lipoproteins),
HDL (high density lipoproteins)
What gives blood a creamy appearance?
High levels of chylomicrons
What are apolipoproteins?
Each lipoprotein class has a complement of associated proteins = A-H = apolipoproteins.
Integral: through phospholipid bilayer
Peripheral: on top
Function =
1) package hydrophobic lipid.
2) enzyme co-factors.
3) ligands.
How does VLDL change to LDL?
Through the addition of different apolipoproteins and by coming into contact with lipoprotein lipase LPL = triglycerides lost = when cholesterol content is greater than content of triglyceride = LDL
How is LDL linked to atherosclerosis?
Oxidised LDL is taken up by macrophages = become foam cells = contribute to formation of plaques
What is the function of LDL?
Provide cholesterol from liver to peripheral tissue
What is the function of chylomicrons?
Transport dietary triacylglycerol from intestine to adipose
Outline the role of VLDL
Transport triacylglycerol synthesised in liver to adipose
Describe the function of IDL
Transport cholesterol synthesised in liver to tissues
What is the function of HDL?
Transport excess cholesterol to liver for disposal in bile salts and to cell requiring additional amounts
Explain how disturbances to the transport of lipids can lead to clinical problems
Oxidised LDL is taken up by macrophages = become foam cells = contribute to formation of atherosclerotic plaques = rupture = thrombosis = stroke/MI.
Hypercholesterolemia = depositions = xanthelasma: yellow patches on eyelids, tendon xanthoma = nodules on tendons, corneal arcus = white circles around eyes
Explain how hyperlipoproteinaemias may be treated
Diet = reduce cholesterol intake.
Lifestyle = stop smoking, start exercising.
Statins = reduce cholesterol synthesis.
Bile salt sequestrants = bind bile salts in GI forcing liver to make more bile salts using up more cholesterol
How do statins work?
Inhibits HMG-CoA reductase needed for the first step in cholesterol synthesis
Which lipoprotein contains the most cholesterol?
LDL
Which enzyme releases FA from chylomicrons?
Lipoprotein lipase
By what mechanism are LDL taken up by peripheral tissues?
Receptor mediated endocytosis
What is a normal plasma [cholesterol], and the units?
<5mmol/L
What is a cholesterol ester?
Cholesterol + fatty acid = ester - for transport
Outline the role of apoB-48
Added to chylomicrons before entering lymphatic duct
Prod from same mRNA as ApoB100 = RNA editing adding premature stop codon
What are the characteristics of LDL?
Do not have ApoC or ApoE
Long half life = more susceptible to oxidative damage (macrophages then foam cells then atherosclerotic plaques)
What are the defects in hyperlipoproteinaemias I, IIa, III?
I = lipoprotein lipase defect
IIa = LDL receptor defect
III = ApoE defect (associated with CHD)
What are the signs of hypercholesterolaemia?
Xanthelasma
Tendon xanthoma
Corneal arcus