Triacylglycerols hepatic

Much of our need for fatty acids as constituents of phospholipids and other complex lipids is met by the diet. In addition, certain lipogenic tissues are capable of the de novo synthesis of fatty acids (Figure 6). These tissues include liver (hepatocytes), adipose tissue, and lactating mammary gland. Much of the fatty acids synthesized by all three tissues is incorporated into triacylglycerol. Hepatic synthesis is primarily for export to other tissues (in very low-density lipoproteins), while synthesis in adipocytes and mammary gland is for local storage. 

Fmctose bypasses the main regulatory step in glycolysis, catalyzed by phosphofmctokinase, and stimulates fatty acid synthesis and hepatic triacylglycerol secretion. 

Figure 25-2. The formation and secretion of (A) chylomicrons by an intestinal cell and (B) very low density lipoproteins by a hepatic cell. (RER, rough endoplasmic reticulum SER, smooth endoplasmic reticulum G, Golgi apparatus N, nucleus C, chylomicrons VLDL, very low density lipoproteins E, endothelium SD, space of Disse, containing blood plasma.) Apolipoprotein B, synthesized in the RER, is incorporated into lipoproteins in the SER, the main site of synthesis of triacylglycerol. After addition of carbohydrate residues in G, they are released from the cell by reverse pinocytosis. Chylomicrons pass into the lymphatic system. VLDL are secreted into the space of Disse and then into the hepatic sinusoids through fenestrae in the endothelial lining.

Medium-chain fatty acids are also present in bovine milk and some plant oils (e.g. coconut). After digestion of the triacylglycerol, they are taken up by the enterocytes in the small intestine but are not esterified. Instead they pass directly into the hepatic portal blood, from where they are taken up by the liver for complete oxidation or conversion to ketone bodies. 

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. 

Cholesterol ester transfer protein catalyses the transfer of triacylglycerol from VLDL or chylomicrons to LDL and to HDL. However, it is the removal of this triacylglycerol from LDL and HDL, which occurs in the liver, via hepatic lipase, that causes problems small and dense LDL particles, which are more atherogenic than normal... 

Cunnane SC. 1987. Hepatic triacylglycerol accumulation induced by ethanol and carbon tetrachloride interactions with essential fatty acids and prostaglandins. Alcoholism Clin Exp Res 11 25-31. 

Modification of nascent chylomicron particles The particle released by the intestinal mucosal cell is called a "nascent" chylomicron because it is functionally incomplete. When it reaches the plasma, the particle is rapidly modified, receiving apo E (which is recognized by hepatic receptors) and C apolipoproteins, The latter include apo C-ll, which is necessary for the activation of lipoprotein lipase, the enzyme that degrades the triacylglycerol contained in the chylomicron (see below). The source of these apolipoproteins is circulating HDL (see Figure 18.16). 

VLDLs are produced in the liver (Figure 18.17). They are composed predominantly of triacylglycerol, and their function is to carry this lipid from the liver to the peripheral tissues. There, the triacylglycerol is degraded by lipoprotein lipase, as discussed for chylomicrons (see p. 226). [Note "Fatty liver" (hepatic steatosis) occurs in conditions in which there is an imbalance between hepatic triacylglycerol synthesis and the secretion of VLDL. Such conditions include obesity, uncontrolled diabetes mellitus, and chronic ethanol ingestion.]... 

Increased protein synthesis The body cannot store protein in the same way that it maintains glycogen or triacylglycerol reserves. However, a transient increase in the synthesis of hepatic proteins does occur in the absorptive state, resulting in replacement of ary proteins that may have been degraded during the previous postabsorptive period (see Figure 24.3, ) ... 

Both lipoprotein lipase and the less well understood hepatic lipase are related structurally to pancreatic lipase.42,4213 In addition to hydrolysis of the triacylglycerols, the uptake of materials from lipoproteins probably involves shedding of intact phospholipids, perhaps as liposome-like particles 40... 

Letexier, D., Diraison, F., and Beylot, M., Addition of inulin to a moderately high-carbohydrates diet reduces hepatic lipogenesis and plasma triacylglycerol concentrations in humans, Am. J. Clin. Nutr., 77, 559-564, 2003. 

Kobayashi, T., Shimizugawa, T., Osakabe, T., Watanabe, S., Okuyama, H. 1997. A long-term feeding of sphingolipids affected the levels of plasma cholesterol and hepatic triacylglycerol but not tissue phospholipids and sphingolipids. Nutr. Res. 17, 111-114. 

Deckelbaum, R. J., Hamilton, J. A., Moser, A., Bengtsson-Olivecrona, G., Butbul, E., Carpentier, Y. A., Gutman, A., and Olivecrona, T. (1990), Medium-chain versus long-chain triacylglycerol emulsion hydrolysis by lipoprotein hpase and hepatic lipase Implications for the mechanisms of lipase action, Biochemistry, 29,1136-1142. 

Types of lipids can also affect toxicant metabolism, as a high proportion of phospholipids is unsaturated due to the presence of linoleic acid (18 2) in the /3-position of triacylglycerol. Thus, dietary 18 2 is important in determining the normal levels of hepatic cytochrome P-450 concentration and the rate of oxidative demethylation in rat liver. 

Yeh, Y.Y. and Yeh, S.M. (1994) Garlic reduces plasma lipids by inhibiting hepatic cholesterol and triacylglycerol synthesis. Lipids. 29 189-193. 

Although PLAj activity has been detected in many mammalian tissues and cells [7-14], only a few PLAjS have been purified and cloned. Some Upases that hydrolyze triacylglycerol such as hepatic lipase and lipoprotein hpase also show PLA, activity [15]. However, these lipases will not be considered here. 

D. Wiggins and G. F. Gibbons, The lipolysis/esterification cycle of hepatic triacylglycerol. Its role in the secretion of very-low-density lipoprotein and its response to hormones and sulphonylureas, Biochem. J., 1992, 284, 457-462. 

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