Transport of Lipids in the Body Fluids
Almost all the fats in the diet, with the principal excep-tion of a few short-chain fatty acids, are absorbed from the intestines into the intes-tinal lymph. During digestion, most triglycerides are split into monoglycerides and fatty acids. Then, while passing through the intestinal epithelial cells, the mono-glycerides and fatty acids are resynthesized into new molecules of triglycerides that enter the lymph as minute, dispersed droplets called chylomicrons, whose diame-ters are between 0.08 and 0.6 micron. A small amount of apoprotein B is adsorbed to the outer surfaces of the chylomicrons. This leaves the remainder of the protein molecules projecting into the surrounding water and thereby increases the suspen-sion stability of the chylomicrons in the lymph fluid and prevents their adherence to the lymphatic vessel walls.
Most of the cholesterol and phospholipids absorbed from the gastrointestinal tract enter the chylomicrons. Thus, although the chylomicrons are composed prin-cipally of triglycerides, they also contain about 9 per cent phospholipids, 3 per cent cholesterol, and 1 per cent apoprotein B. The chylomicrons are then transported upward through the thoracic duct and emptied into the circulating venous blood at the juncture of the jugular and subclavian veins.
About 1 hour after a meal that contains large quantities of fat, the chylomicron concentration in the plasma may rise to 1 to 2 per cent of the total plasma, and because of the large size of the chylomicrons, the plasma appears turbid and sometimes yellow. However, the chylomi-crons have a half-life of less than 1 hour, so the plasma becomes clear again within a few hours. The fat of the chylomicrons is removed mainly in the following way.
Chylomicron Triglycerides Are Hydrolyzed by Lipoprotein Lipase, and Fat Is Stored in Adipose Tissue and Liver Cells. Most of thechylomicrons are removed from the circulating blood as they pass through the capillaries of adipose tissue or the liver. Both adipose tissue and the liver contain large quantities of the enzyme lipoprotein lipase. This enzyme is especially active in the capillary endothelium, where it hydrolyzes the triglycerides of chylomicrons as they come in contact with the endothelial wall, thus releas-ing fatty acids and glycerol.
The fatty acids, being highly miscible with the mem-branes of the cells, immediately diffuse into the fat cells of the adipose tissue and into the liver cells. Once inside these cells, the fatty acids are again synthesized into triglycerides, with new glycerol being supplied by the metabolic processes of the storage cells. The lipase also causes hydrolysis of phospholipids; this, too, releases fatty acids to be stored in the cells in the same way.
When fat that has been stored in the adipose tissue is to be used elsewhere in the body to provide energy, it must first be transported from the adipose tissue to the other tissue. It is transported mainly in the form of free fattyacids. This is achieved by hydrolysis of the triglyceridesback into fatty acids and glycerol.
At least two classes of stimuli play important roles in promoting this hydrolysis. First, when the amount of glucose available to the fat cell is inadequate, one of the glucose breakdown products, a-glycerophosphate, is also available in insufficient quantities. Because this substance is required to maintain the glycerol portion of triglycerides, the result is hydrolysis of triglycerides. Second, a hormone-sensitive cellular lipase can be acti-vated by several hormones from the endocrine glands, and this also promotes rapid hydrolysis of triglycerides.
On leaving fat cells, fatty acids ionize strongly in the plasma, and the ionic portion combines immediately with albumin molecules of the plasma proteins. Fatty acids bound in this manner are called free fatty acids or nonesterified fatty acids, to distinguish them from other fatty acids in the plasma that exist in the form of (1) esters of glycerol, (2) cholesterol, or (3) other substances.
The concentration of free fatty acids in the plasma under resting conditions is about 15 mg/dl, which is a total of only 0.45 gram of fatty acids in the entire circu-latory system. Strangely enough, even this small amount accounts for almost all the transport of fatty acids from one part of the body to another for the following reasons:
1.Despite the minute amount of free fatty acid in the blood, its rate of “turnover” is extremely rapid: half the plasma fatty acid is replaced bynew fatty acid every 2 to 3 minutes. One cancalculate that at this rate, almost all the normal energy requirements of the body can be provided by the oxidation of transported free fatty acids, without using any carbohydrates or proteins for energy.
2.Conditions that increase the rate of utilization of fat for cellular energy also increase the free fatty acid concentration in the blood; in fact, the concentration sometimes increases fivefold to eightfold. Such a large increase occurs especially in cases of starvation and in diabetes; in both theseconditions, the person derives little or no metabolic energy from carbohydrates.
Under normal conditions, only about 3 molecules of fatty acid combine with each molecule of albumin, but as many as 30 fatty acid molecules can combine with a single albumin molecule when the need for fatty acid transport is extreme. This shows how variable the rate of lipid transport can be under different physiologic conditions.
In the postabsorptive state, after all the chylomicrons have been removed from the blood, more than 95 per cent of all the lipids in the plasma are in the form of lipoprotein. These are small particles—much smaller than chylomicrons, but qualitatively similar in composition—containing triglycerides, cholesterol,phospholipids, and protein. The total concentrationof lipoproteins in the plasma averages about 700 mg per 100 ml of plasma—that is, 700 mg/dl. This can be broken down into the following individual lipoprotein constituents:
Types of Lipoproteins. Aside from the chylomicrons, whichare themselves very large lipoproteins, there are four major types of lipoproteins, classified by their densities as measured in the ultracentrifuge: (1) very low densitylipoproteins, which contain high concentrations oftriglycerides and moderate concentrations of both cho-lesterol and phospholipids; (2)intermediate-densitylipoproteins, which are very low density lipoproteinsfrom which a share of the triglycerides has been removed, so that the concentrations of cholesterol and phospholipids are increased; (3) low-density lipopro-teins, which are derived from intermediate-densitylipoproteins by the removal of almost all the triglyc-erides, leaving an especially high concentration of cholesterol and a moderately high concentration of phospholipids; and (4) high-density lipoproteins, which contain a high concentration of protein (about 50 per cent) but much smaller concentrations of cholesterol and phospholipids.
Formation and Function of Lipoproteins. Almost all thelipoproteins are formed in the liver, which is also where most of the plasma cholesterol, phospholipids, and triglycerides are synthesized. In addition, small quanti-ties of high-density lipoproteins are synthesized in the intestinal epithelium during the absorption of fatty acids from the intestines.
The primary function of the lipoproteins is to trans-port their lipid components in the blood. The very low density lipoproteins transport triglycerides synthesized in the liver mainly to the adipose tissue, whereas the other lipoproteins are especially important in the dif-ferent stages of phospholipid and cholesterol transport from the liver to the peripheral tissues or from the periphery back to the liver. Later, we discuss in more detail special problems of cholesterol transport in relation to the disease atherosclerosis, which is associated with the development of fatty lesions on the insides of arterial walls.
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