Introduction to Lipid Transport and Regulation of Uptake Flashcards
What are n-6 series acids? Give examples.
These are acids obtained from terrestrial plants. Although the most common n-6 acid is linoleic acid 18:2n-6, the most important for proper bodily function is arachidonic acid 20:4n-6.
What is arachidonic acid important for?
This is important for making inositol phosphoglycerides and in this role it can, if stimulated into cleavage by cytokines or hormones, be converted into the signalling molecules known as eicosanoids.
Depending on what it is stimulated by, this could cause a signalling cascade with a variety of effects. Ultimate products of the cleaved arachidonic acid include α prostaglandin and α leukotriene, produced by the enzymes cyclooxygenase and 5-lipoxygenase respectively.
A prostaglandin is involved in pain signalling, hence the effectiveness of aspirin which acts by inhibiting cyclooxygenase.
How are n-3 series acids obtained?
Acids such as α-linolenic are found in marine cold-water plant life, often obtained in the human diet through consumption of herbivorous fish. These fish modify the acids, meaning that the majority of the acids humans consume are DHA and EPA.
Give two examples of n-3 series acids and their roles.
DHAs (22:6n-3) are high in the phospholipids required for brain and retinal function. They are very flexible acids that are thought to be involved in the function of membrane embedded proteins.
EPAs (20:5n-3) acts as both an anti-thrombotic and anti-inflammatory, which is thought to be due to it competing with arachidonic acid for incorporation into phospholipids.
What are PUFAs?
The primary role of these fatty acids is in regulation of gene expression, largely repressing genes involved in lipogenesis and stimulating those involved in lipid oxidation. This is generally carried out through binding of the acids to nuclear receptors that in turn bind to response elements on the DNA.
One such group of nuclear receptors are PPARs, stimulation of which causes dimerisation with retinoid X receptors (RXRs) and subsequent binding to DNA response elements called PPREs (peroxisome proliferator hormone response elements).
What structural feature solubilises cholesterol?
Cholesterols possess a single hydroxyl group at one end, allowing them to orient themselves in mono- or bilayer lipid membranes by inserting the OH into the phosphate head layer. In lipid membranes it is often used to provide mechanical stability, and is often carried in the membrane of the lipoproteins. The hydroxyl also allows for esterification of fatty acids to the cholesterol.
Describe the VLDL cascade.
Nascent VLDL released from the liver contains ApoB100, apoC1, apoE, CH, CE, and TG. As it circulates in blood, it picks up apoC-II enabling LPL activation and additional apoE donated from high-density lipoprotein (HDL).
At this point, nascent VLDL becomes a mature VLDL. Once in circulation, VLDL will come in contact with lipoprotein lipase (LPL) in the capillary beds in the peripheral tissues and have its TG harvested.
Upon leaving the capillaries as an IDL it donates the ApoCII to HDLs, but retains ApoE for uptake by LDLRs in both the liver and peripheral tissues (~50% of the population).
Further lipids can be removed both by CETP and Hepatic Lipase to produce an LDL which leads to loss of ApoE and thus reduced LDLR uptake.
