Plasma Lipoprotein Transport



Plasma Lipoprotein Transport

INTRODUCTION:

A discussion and understanding of plasma lipoprotein synthesis and transport is essential to understanding the lipogenic mechanisms that can contribute to atherosclerotic plaque in the body. Although the process of synthesis and transport involves several processes going on simultaneously we’re going to break it down into steps in order to simplify its explanation. So, we’ll begin by the digestion of fats in the digestive tract or gut.

Chapter I:

A:

The liver and the gut are the two major organs of lipoprotein synthesis and transport. They are connected by a cystic duct which empties bile from the gallbladder into the gut. The bile is formed in the liver, and stored in the gallbladder until a meal with fat enters the upper small intestine. Bile salts in the bile help emulsify the fats so they can be more easily digested and absorbed in the gut. Within the epithelial cells of the gut wall, a combination of triglycerides, and cholesterol, and fatty acids are coated with protein to form large lipoproteins known as chylomicrons.

B:

Chylomicrons are absorbed into the lymphatic system, which eventually drains into the circulation. Chylomicrons then circulate to the liver where they are absorbed and broken down to contribute to the triglyceride and the cholesterol pool within the liver.

C:

Bile salts are not absorbed into the gut wall along with the fats, but remain in the upper small intestine. The bile salts continue down the small intestine until they reach the terminal end of the small intestine, called the ileum. It is in the ileum that most of the bile salts are reabsorbed, entering the circulation in one of the original recycling efforts of the body. Bile salts are carried by the circulation back to the liver and are then stored once again with bile in the gallbladder to be utilized for future emulsification of fats in the gut. Bile salts which are not reabsorbed in the ileum are carried into the colon, and eventually exit the body with the fecal waste. To replace these lost bile salts, the liver will synthesize more from its cholesterol pool.

D:

In addition to dietary sources of cholesterol absorbed in the gut and delivered to the liver by chylomicrons, another major contributor to the cholesterol pool is cholesterol synthesis by the cells of the liver. Liver synthesis of cholesterol is roughly inverse to the amount of cholesterol contributed by the diet through chylomicrons. In other words, the liver synthesizes cholesterol even in the total absence of cholesterol in the diet. With an increased intake of cholesterol in the diet, there is a somewhat reduced synthesis of cholesterol in the liver, keeping the total cholesterol pool roughly constant. Liver synthesis of cholesterol is stimulated by a number of other factors, including diet and genetics.

Chapter II

E:

The liver’s cholesterol pool, regardless of the source, is used in two major ways. It’s used to form bile salts, which as we have seen, are then stored in the gallbladder as a part of the bile, and eventually emptied into the gut. The bile salts emulsify fats and help in fat digestion and absorption in the gut.

F:

The other use of cholesterol by the liver is to supply cholesterol for the rest of the body’s needs. In order to do this, cholesterol from the liver’s pool is combined with triglycerides and coated with a special protein that makes it soluble in our blood. These rather large molecular structures are called very low density lipoproteins, or VLDL, and they are released from the liver into the circulation to supply the body’s needs for triglycerides and cholesterol.

G:

Lipoprotein lipase is an enzyme found throughout the body, with high amounts in the arterial walls. Lipoprotein lipase helps to strip off triglycerides from the VLDL. Those triglycerides can be used in various tissues throughout the body. As triglycerides are removed from the VLDL, the VLDL gets smaller and becomes enriched with a higher percentage of its composition as cholesterol. In this stage the lipoproteins are referred to as intermediate density lipoproteins, or IDL. Further removal of triglycerides from IDL enriches the percentage of cholesterol even more, and results in an even more compact molecule called low density lipoprotein.

H:

Low density lipoprotein, or LDL, is thus formed by the removal of triglycerides from both VLDL and IDL in the circulation. The resulting LDL has a high percentage of cholesterol and still has its protein coating. The protein coating on the LDL allows it to interact with tissues that utilize the large amounts of cholesterol contained within this lipoprotein.

I:

Tissues that use large amounts of cholesterol have receptors on their cell surface that allow it to interact with LDL protein and receive cholesterol from the LDL. These regulated receptors are found on the cells of the adrenal glands, the gonads, the liver, and arterial lining throughout the body. Cholesterol metabolism begins in these tissues by the dropping off of cholesterol from LDL. The products of cholesterol metabolism include sex steroids, adrenal cortical steroids, Vitamin D, bile salts, and plasma membrane structures in all cells.

J:

The regulated receptors on the liver will help return some of the cholesterol to the liver from unused LDL. There are genetic changes in these regulated receptors and various tissues that allow LDL to accumulate within the circulation in large amounts. LDL is the so-called “bad cholesterol” and genetic differences in these regulated receptors can result in the accumulation or large amounts of LDL in the circulation. One such known genetic difference results in the condition of familial hyper-cholesterolemia.

Chapter III

K:

LDL within the circulation is subject to action by free radicals throughout the body. Free radicals are highly oxidative molecules that can oxidize LDL, one of the initial steps in the formation of atherosclerotic plaque. Where do free radicals come from? A variety of processes can result in the formation of free radicals within our body. For instance certain foods such as alcohol result in the formation of large amounts of free radicals. Exercise also causes the formation of free radicals and can increase oxidation of LDL. Free radicals also are formed by various pollutants. Tobacco, for instance, contains a number of toxic chemicals that form free radicals in our circulation and therefore increase oxidation of LDL. Free radical formation and oxidation can be combated by antioxidant molecules within our body, many of which are formed from vitamins and other nutrients in our diet. Vitamins C, E, and A are some important antioxidant molecules which act to reduce free radical formation and action, therefore reducing the oxidation of LDL.

L:

The reason that oxidized LDL is undesirable is because it is recognized by macrophage cells throughout the body that have receptors on their surface. Macrophage cells gather in areas of inflammation following injury, one of these areas being the endothelial lining of large-and medium-sized arteries. The macrophage cells have specialized scavenger receptors on their surface which recognize and absorb oxidized LDL. The cholesterol and triglycerides become a part of the macrophage cell, which then attempts to “digest” the excess molecules using its lysosomal activity.

M:

The macrophage cells having absorbed excessive oxidized LDL take on a foamy appearance and become foam cells, which die within the tissues. These dead macrophage cells are no longer capable of breaking down any of the fat and cholesterol, so it remains within the tissues the foam cells are found in. Foam cells are the characteristic first sign of atherosclerotic plaque forming white streaks under the arterial lining called the endothelium.

Chapter IV

N:

Another lipoprotein formed by the liver is called high density lipoprotein, sometimes referred to as the “good cholesterol.” High density lipoprotein is formed with very small amounts of cholesterol, small amounts of triglyceride and a special protein coat within the liver that makes it distinct from the VLDL, also formed in the liver. The HDL in the circulation acts like a sponge in picking up excess cholesterol from tissues that normally metabolize cholesterol but are receiving more than they can possibly use. An enzyme important in this process of reverse cholesterol transport is called lecithin-cholesterol acyl transferase. LCAT stimulates reverse cholesterol transport from tissues that have excessive amounts of cholesterol into the HDL molecules.

O:

Left over cholesterol from adrenal tissue, gonadal tissue, liver, and arteries all can be absorbed by the HDL, which acts something like a sponge. It has also been discovered that even oxidized LDL in the foam cells can, to some degree, be removed by the enzyme lecithin-cholesterol acyl transferase (LCAT) and HDL. Evidence suggests that it may be possible to reduce the development of atherosclerotic plaques, especially in their initial stages of formation, before scarring and calcification of the plaques has developed. Elevated levels of HDL in the circulation will absorb the cholesterol, even the oxidized LDL cholesterol found in atherosclerotic plaque, as long as the cholesterol remains available to the actions of the enzyme and HDL.

P:

As HDL absorbs cholesterol from many tissues it becomes mature and it returns to the liver. The lipoprotein coat of HDL helps the liver recognize it, and direct the cholesterol to the liver pool. In addition, there is some small exchange of cholesterol from HDL to LDL while it’s in the blood.

ALL:

As we’ve seen in this discussion of plasma lipoprotein transport and synthesis, there are good and bad forms of lipoproteins in terms of their effect in the formation of atherosclerotic plaque. The physiological function of LDL is not to form plaque, but to deliver cholesterol to those tissues that utilize it. When the LDL is oxidized by free radicals it can become an important component of foam cells. Accumulation of these foam cells at an inflammatory site in our blood vessels can lead to atherosclerotic plaque. That plaque can lead to coronary artery disease and other forms of atherosclerosis that are the leading cause of death in the United States. HDL, the so-called “good cholesterol,” is a normal physiological component of our metabolism to help balance the excessive cholesterol that would be left in tissues if we had too much in our diet, as many of us do. HDL is capable of helping us maintain a good balance of cholesterol delivery and removal. There are many risk factors for atherosclerosis that can be related to the factors of synthesis and transport that we’ve discussed here, and many others that can be explored with further study.

................
................

In order to avoid copyright disputes, this page is only a partial summary.

Google Online Preview   Download