Koo,

OK. I was trying to keep it simple. Now for more information than you probably wanted. There are two major classeses of lipoproteins: those containing apolipoprotein-AI (apo-AI) and those containing apolipoprotein-B (apoB).

The apo-AI containing lipoproteins are HDL. Although HDL particle size can vary and there is some evidence of functional differences between the small HDL and large HDL, they are clinically grouped together to give you an HDL-cholesterol value that sums them all up.

The apo-B containing lipoproteins are more complex. When we eat, the intestine packages and secretes an apoB-containing lipoprotein called a chylomicron. Chylomicrons contain a form of apoB called apoB48. These chylomicrons are transient molecules that will be cleared from the circulation in the post-meal phase. That's why docs want you to give a fasting blood sample....to get rid of these guys. The liver-derived apoB-containing lipoproteins are the ones we are looking at with our fasting blood sample and comprise the "non-HDL cholesterol" term that I used. These liver-derived particles contain a form of apoB called apoB100. ApoB100 and apoB48 are both derived from the same gene, but there is an mRNA editing enzyme in the intestine that modified the mRNA so that the protein product is shorter (apoB48) than the longer form (apoB100). 

ApoB-containing lipoproteins are assembled inside the cell prior to secretion. This is distinct from the apoAI/HDL pathway, in which the nascent apoAI molecule is secreted and then accumulates more cholesterol/phospholipid while in the circulation. ApoB-containing lipoproteins get loaded with a core of triglycerides and cholesterol esters. The size of this "core" can be variable.  The larger the core, the lower the density (easier to float). The largest secreted apoB particles will have the lowest density, and are called very-low density lipoproteins (VLDL). This is the major apoB particle that the liver secretes; however, some intermediary-density lipoproteins (IDL) get assembled and secreted as well. IDL are a wee bit smaller than VLDL, but both still larger than low-density lipoproteins (LDL). In the circulation, VLDL and IDL are metabolized by lipases (enzymes that break down fat) in a way that delivers triglycerides from the core to peripheral tissues. This both shrinks the size of the core of the VLDL/IDL and enriches the core for cholesterol ester. These smaller, more dense particles are LDL. LDL survive in the circulation longer relative to VLDL/IDL. So most of the "non-HDL cholesterol" in a fasting blood sample will be LDL. If one has a normal fasting triglyceride measurement, then most likely the contributioin of VLDL/IDL cholesterol to the non-HDL cholesterol number is negligible. However, if one has a fasting triglyceride value in the high normal or above normal range, then one may expect the contribution of the VLDL/IDL to the non-HDL cholesterol to be higher, since it will be the VLDL/IDL particles contributing to the increased plasma triglyceride.....and this VLDL/IDL core also contains cholesterol ester. To make things even more complicated, there are various subclasses of LDL. In general, the larger LDL don't present as much cardiovascular risk as the smallest, most dense LDL.

More info than you probably wanted, but hopefully that addresses your question. Now to catch up on today's news release and commentary on the Agoracom board!

BearDownAZ