Collisions occur between lipoproteins in circulation. Core contents are exchanged along their concentration gradients with some particles enlarging and others shrinking. Of concern is the production of HDLs that are so small they can be lost via excretion by the kidneys.
At the lower left corner of the diagram is a small, cholesterol ester-rich HDL3. The previous tutorial described its conversion to a larger sphere after picking up free cholesterol from a cholesterol-rich body cell. The enlargement leading to HDL2 involves SR-B1, LCAT and PLTP .
Included in this diagram is a large foam cell that has numerous cholesterol droplets. Foam cells form when macrophages become trapped beneath the endothelial lining of arteries and accumulate excessive cholesterol. If the droplets become too abundant an atherosclerotic plaque will develop. HDLs get their 'good cholesterol' label because they can remove free cholesterol from these cells just as they do from other cells.
In addition to the common SR-B1 transporter, foam cells have another transporter called ATP-binding cassette transporter G-1 (ABCG-1). This transporter functions in a manner similar to that of ABCA-1. It places rafts of free cholesterol in the foam cell's outer leaflet. LCAT facilitate the conversion of the new free cholesterol into cholesterol ester and PLTP adds additional coat material as sphere continues to enlarge.
There are frequent collisions (indicated by curved arrows coming together) among the various lipoproteins while circulating. There is evidence that a plasma protein called cholesterol ester transfer protein (CETP) binds lipoproteins and forms a hydrophobic channel between their cores. This allows diffusion of core lipids -- triglyceride and cholesterol ester -- to be exchanged between triglyceride-rich and cholesterol ester-rich lipoproteins.
As an example, the diagram shows what would result if an IDL and an HDL were involved in such a collision. Clearly the triglyceride (lavender) gradient favors diffusion from the IDL into the HDL and the cholesterol ester gradient favors diffusion in the opposite direction. After separation the IDL is shown having less triglyceride and more cholesterol ester while the HDL now has some triglyceride in its core.
In addition to the change in core composition of each particle there is also a size change. Because a triglyceride molecule occupies more space than a cholesterol ester molecule the HDL has enlarged and the IDL has shrunk. Note this change in the diagram.
Hepatic lipase (HL) is a plasma enzyme that hydrolyzes triglycerides into free fatty acids and glycerides. It also has phospholipid activity and can destroy lipoprotein coats. In this diagram it is shown changing a triglyceride-rich HDL to a smaller HDL3 with no triglyceride left.
A big concern is that an increase in CETP activity will create more HDLs with triglyceride in their core. Since triglyceride will be hydrolyzed by hepatic lipase the particle will shrink. The more triglyceride, the more it will shrink. Then, the smaller the particle the more likely it will be excreted by the kidneys. This means a loss in HDL -- the 'good cholesterol'.
Continue to Low Density Lipoproteins
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