Triacylglycerols transport

Fatty acids Despite the fact that fatty acids are lipid soluble, so that they will diffuse across membranes without a transporter, one is present in the plasma membrane to speed up entry into the cells, so that it is sufficient to meet the demand for fatty acid oxidation. Triacylglycerol transport into cells also depends on the fatty acid transporter. Since it is too large to be transported per se, it is hydrolysed within the lumen of the capillaries in these tissues and the resultant fatty acids are taken up by the local cells via the fatty acid transporter (Chapter 7). Hence the fatty acid transporter molecule is essential for the uptake of triacylglycerol. 

Synthesis and secretion of chylomicrons are directly linked to the rate of dietary fat absorption. When fat is absent from the diet, small chylomicrons with a diameter of about 50 nm are secreted at a rate of approximately 4 g of triacylglycerol per day. On a high-fat diet, the mass of lymphatic triacylglycerol transport may increase 75-fold, owing partly to greater production of chylomicrons but primarily to a dramatic increase in size of the particles, which may have diameters of 1200 nm, and a 16-fold increase in the amount of triacylglycerol within their core. 

VLDL and LDL metabolism II endogenous triacylglycerol transport Lipids and llpid metabolism... 

When most lipids circulate in the body, they do so in the form of lipoprotein complexes. Simple, unesterified fatty acids are merely bound to serum albumin and other proteins in blood plasma, but phospholipids, triacylglycerols, cholesterol, and cholesterol esters are all transported in the form of lipoproteins. At various sites in the body, lipoproteins interact with specific receptors and enzymes that transfer or modify their lipid cargoes. It is now customary to classify lipoproteins according to their densities (Table 25.1). The densities are... 

HDL and VLDL are assembled primarily in the endoplasmic reticulum of the liver (with smaller amounts produced in the intestine), whereas chylomicrons form in the intestine. LDL is not synthesized directly, but is made from VLDL. LDL appears to be the major circulatory complex for cholesterol and cholesterol esters. The primary task of chylomicrons is to transport triacylglycerols. Despite all this, it is extremely important to note that each of these lipoprotein classes contains some of each type of lipid. The relative amounts of HDL and LDL are important in the disposition of cholesterol in the body and in the development of arterial plaques (Figure 25.36). The structures of the various... 

The fatty acids released on triacylglycerol hydrolysis are transported to mitochondria and degraded to acetyl CoA, while the glycerol is carried to the liver for further metabolism. In the liver, glycerol is first phosphorylated by reaction with ATP. Oxidation by NAD+ then yields dihydroxyacetone phosphate (DHAP), which enters the carbohydrate metabolic pathway. We ll discuss this carbohydrate pathway in more detail in Section 29.5. 

Figure 15-6. Transport and fate of major lipid substrates and metabolites. (FFA, free fatty acids LPL, lipoprotein lipase MG, monoacylglycerol TG, triacylglycerol VLDL, very low density lipoprotein.)...

Fat absorbed from the diet and lipids synthesized by the liver and adipose tissue must be transported between the various tissues and organs for utilization and storage. Since lipids are insoluble in water, the problem of how to transport them in the aqueous blood plasma is solved by associating nonpolar lipids (triacylglycerol and cholesteryl esters) with amphipathic hpids (phospholipids and cholesterol) and proteins to make water-miscible hpoproteins. 

TRIACYLGLYCEROL IS TRANSPORTED FROM THE INTESTINES IN CHYLOMICRONS FROM THE LIVER IN VERY LOW DENSITY LIPOPROTEINS... 

HDL concentrations vary reciprocally with plasma triacylglycerol concentrations and directly with the activity of lipoprotein lipase. This may be due to surplus surface constituents, eg, phospholipid and apo A-I being released during hydrolysis of chylomicrons and VLDL and contributing toward the formation of preP-HDL and discoidal HDL. HDLj concentrations are inversely related to the incidence of coronary atherosclerosis, possibly because they reflect the efficiency of reverse cholesterol transport. HDL, (HDLj) is found in... 

Four major groups of lipoproteins are recognized Chylomicrons transport lipids resulting from digestion and absorption. Very low density lipoproteins (VLDL) transport triacylglycerol from the liver. Low-density lipoproteins (LDL) deliver cholesterol to the tissues, and high-density lipoproteins (HDL) remove cholesterol from the tissues in the process known as reverse cholesterol transport. 

Why are triacylglycerols difficult to transport through human blood ... 

Chylomicron 99 80-95 2-6 3-9 1 Transport of fat absorbed in the intestine to the liver and adipose tissues (exogenous triacylglycerol)... 

Very low density lipoprotein (VLDL) 90 40-80 10-40 15-20 5-10 Transport of fat synthesized in the liver (endogenous triacylglycerol)... 

A summary of the sources and fates of fatty acids and ketone bodies is presented in Figure 7.1 and Table 7.1. A major problem with long-chain fatty acids and TAGs is their lack of solubility in the aqueous medium of the blood and interstitial fluid. How this is overcome for fatty acids is discussed in this chapter, and for triacylglycerol in Chapter 11. Unfortunately, the need to transport relatively large quantities of triacylglycerol in the blood can lead to pathological problems (Chapter 11). 

Medium-chain acyl-CoA synthetase, which is present within the mitochondrial matrix of the liver, activates fatty acids containing from four to ten carbon atoms. Medium-chain length fatty acids are obtained mainly from triacylglycerols in dairy products. However, unlike long-chain fatty acids, they are not esterified in the epithelial cells of the intestine but enter the hepatic portal vein as fatty acids to be transported to the liver. Within the liver, they enter the mitochondria directly, where they are converted to acyl-CoA, which can be fully oxidised and/or converted into ketone bodies. The latter are released and can be taken up and oxidised by tissues. 

The physiological pathway for oxidation of fatty acids in organs or tissues starts with the enzyme triacylglycerol lipase within adipose tissue, that is, the hormone-sensitive lipase. This enzyme, plus the other two lipases, results in complete hydrolysis of the triacylglycerol to fatty acids, which are transported to various tissues that take them up and oxidise them by P-oxidation to acetyl-CoA. This provides a further example of a metabolic pathway that spans more than one tissue (Figure 7.13) (Box 7.1). 

The packaging of triacylglycerol into chylomicrons or VLDL provides an effective mass-transport system for fat. On a normal Western diet, approximately 400 g of triacylglycerol is transported through the blood each day. Since these two particles cannot cross the capillaries, their triacylglycerol is hydrolysed by lipoprotein lipase on the luminal surface of the capillaries (see above). Most of the fatty acids released by the lipase are taken up by the cells in which the lipase is catalytically active. Thus the fate of the fatty acid in the triacylglycerol in the blood depends upon which tissue possesses a catalytically active lipoprotein lipase. Three conditions are described (Figure 7.23) ... 

Triacylglycerol in the forms of chylomicrons or very low density lipoproteins constitutes the mass transport system of fat in the blood. Excessive levels, particularly of VLDL, can give rise to various pathological problems which are grouped together under the title lipoproteinaemias and are discussed in Chapter 11 (Appendix 11.9). 

A variety of fuels are available to generate ATP for muscle activity phosphocreatine glycogen (which can be converted to lactic acid or completely oxidised to CO2) glucose (from liver glycogen, transported to the muscle via the blood and completely oxidised to CO2) triacylglycerol within the muscle (completely oxidised to CO2) and fatty acids from triacylglycerol in adipose tissue (completely oxidised to CO2). 

Sugar The hydrolysis of sucrose in the intestine produces both glucose and fructose, which are transported across the epithelial cells by specific carrier proteins. The fructose is taken up solely by the liver. Fructose is metabolised in the liver to the triose phosphates, dihydroxy-acetone and glycer-aldehyde phosphates. These can be converted either to glucose or to acetyl-CoA for lipid synthesis. In addition, they can be converted to glycerol 3-phosphate which is required for, and stimulates, esterification of fatty acids. The resulting triacylglycerol is incorporated into the VLDL which is then secreted. In this way, fructose increases the blood level of VLDL (Chapter 11). 

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