WHAT ON EARTH IS A LIPOPROTEIN?
By Malcolm Kendrick MbChB, MRCGP (email - malcolm~llp.org.uk )
I have written a few columns on heart disease for Red Flags and the response has been very positive. However, there is a major problem that emerges quite clearly from e-mails that I get back. The problem is that there is an enormous level of confusion about the whole area of cholesterol, lipids, lipoproteins, fats etc. So I thought I should provide a simple primer on this area, as it makes debate and discussion a lot easier.
Before getting into the area, I must admit that I have a great deal of sympathy with the confusion. When I first started looking at the diet-heart/cholesterol hypothesis I found the science to be almost totally incomprehensible, and much of this is due to, what I refer to, as terminological inexactitude.
To provide a couple of simple examples. A high level of low density lipoprotein (LDL) in the blood is usually referred to as a high cholesterol level. A high level of very low density lipoprotein (VLDL) in the blood is usually referred to as a high triglyceride level. Frankly this is nuts, as LDL and VLDL contain both triglycerides and cholesterol - and neither triglycerides or cholesterol float free in the blood.
Let’s try another example. An LDL with a protein attached to it called apolipoprotein b-100 is called LDL. LDL with a protein attached to it called apolipoprotein (a) is called Lipoprotein (a). Or Lp(a)…. I sense confusion arising.
So, let’s start at the very beginning, it’s a very good place to start. Point number one. cholesterol is not a fat; it is called many different things, even an alcohol, but one thing it is not, is a fat, or a fatty acid. (Fats and fatty acids are the same thing, by the way). Nor can you make cholesterol from fats.
Cholesterol starts life as a chemical called Acetyl coenzyme a. A relatively ubiquitous building block that is used to make all sorts of things that the body needs. The vast majority of cholesterol in your body is synthesised by the liver from Acetyl coenzyme a. You only get about a quarter of your cholesterol from dietary sources.
Point number two: Triglycerides are three fat molecules stuck to a Glycerol molecule - which is where the tri and the glyceride come from. Although the fat part seems to have gone missing in the nomenclature. Most fats are transported around the body and stored as triglycerides.
When you eat cholesterol and/or fat, they are absorbed by the gut. But neither fat/triglyceride, nor cholesterol can be dissolved in blood - they are insoluble in water. So, they have to be wrapped up in a sphere known as a lipoprotein in order to transport them out of the gut.
Point three: Lipoproteins come in many sizes. The biggest is a chylomicron and the smallest is a high density lipoprotein (HDL). If a chylomicron were the size of a football (soccer ball), a VLDL would be the size of a baseball, an LDL would be the size of a golf ball, and an HDL the size of a pea, perhaps even a petit pois.
All lipoproteins contain cholesterol and triglyceride - in varying proportions. The basic function of a lipoprotein is to carry triglycerides from the gut, or the liver, to fat cells, where the triglyceride is then stored and used for energy when needed - in situations such as pressing the remote control for the television, or chewing a hamburger.
Lipoproteins also transport cholesterol and triglycerides to the liver. When a chylomicron reaches the liver, from the gut, it is grabbed, absorbed, and then smashed to pieces. The liver then reconstructs the component parts into VLDLs and sends them out into the bloodstream with an apolipoprotein b-100 protein stuck to the side.
As a VLDL travels around the body, fat cells snatch at it, chop bits off and it gets smaller and smaller, turning first into an intermediate density lipoprotein (IDL), then a low density lipoprotein (LDL). Once the lipoprotein has reached LDL size, it is either re-absorbed by the liver and re-used, or it is absorbed by other cells around the body that are in need of cholesterol.
The reason why LDL can be absorbed is all to do with the apolipoprotein b-100. This is the protein ‘key’ that the cells recognise. It is the key that fits exactly into the LDL receptor on the cell wall. Once the b-100 molecule locks to the receptor, the receptor closes around the LDL, draws it into the cell where the LDL is broken down into its component parts.
And what of High Density Lipoprotein (HDL)? HDL is not part of the same metabolic ‘loop’ as the other forms of lipoproteins. It is made separately, and appears to act as a cholesterol mop, scavenging loose cholesterol from broken down cells and suchlike, and transporting it back to the liver. Which is why it is often called ‘good’ cholesterol. It is called this even though HDL isn’t cholesterol, and cannot possibly have any effect on removing cholesterol deposits from arterial walls. In short, it is neither cholesterol, nor good. Apart from that it is a magnificently accurate form of nomenclature.
Anyway. In short, lipoproteins are the ‘taxis’ that are used to transport insoluble cholesterol and triglyercides around the body. Apart from HDL, lipoproteins start big, as chylomicrons, and gradually get smaller as they lose triglyceride. The VLDLs, produced by the liver get smaller and smaller until they become LDLs. At which point they are reabsorbed into the liver, or other cells.
What then, is the cholesterol level?
Well, it should be obvious by now that the cholesterol level doesn’t actually exist. For there is no cholesterol free in your bloodstream. You can have a level of LDL, or VLDL, or chylomicrons, but you can’t have a level of cholesterol. And so all measurements of ‘cholesterol’ are actually measurement of lipoproteins - which is where most of the terminological confusion arises.
Thus, when someone uses the term ‘total’ cholesterol, what they mean is the level of LDL, plus HDL, plus a few other lipoproteins e.g. Lipoprotein (a) and/or some intermediate density lipoproteins that aren’t quite LDLs, but get mixed up in the process.
When the term LDL/cholesterol, or ‘bad’ cholesterol level is used, this refers only to the level of LDL. This is usually about two thirds the level of ‘total’ cholesterol. Other laboratories will tell you both the LDL and HDL (good cholesterol) level, and give you the proportion of LDL to HDL. With a ratio greater than three seen as ‘bad’ and a ratio less than three as ‘good.’ This can be presented as LDL:HDL 3.2:1, or whatever.
Some people think the level of VLDL is important, and they will give you this measurement as well. But they will call it the level of triglyceride.
I think that is enough for one article. I hope that you find it a helpful dash through the nomenclature used in this area. If I get some positive feedback I could explain the difference between saturated fats and unsaturated fats, and what the terms Omega 3 and Omega 6 actually mean, and a few other things as well.
Hope this article helps. There's another one on saturated fats if you're interested, let me know.
|
Clarification
Linear Mode
