Glycerol triacylglycerols synthesized

Figure 32-3. Schematic representation of fuel mobilization during fasting. Catabolism of muscle proteins provides alanine for gluconeogenesis and glutamine for utilization by the gut and kidney, while branched chain amino acids are primarily oxidized within the muscle. Breakdown of adipocyte triacylglycerols provides glycerol and free fatty acids (not shown) the free fatty acids provide fuel for liver, muscle and most other peripheral tissues. The liver utilizes both alanine and glycerol to synthesize glucose which is required for the brain and for red blood cells (not shown). Adapted from Besser and Thirner (2002).

The enzymes for phosphatidate synthesis, acyl CoA synthetase, glycerol 3-phosphate acyltransferase and monoacylglycerol acyltransferase, are on both the outer mitochondrial membrane and the endoplasmic reticulum membrane. Diacylglycerol acyltransferase is only on the endoplasmic reticulum it may use either diacylglycerol phosphate synthesized on the endoplasmic reticulum or that synthesized on the mitochondrion. Triacylglycerol synthesized on the endoplasmic reticulum membrane may then enter lipid droplets either in the cytosol or, in the liver and intestinal mucosa, the lumen of the endoplasmic reticulum for assembly into lipoproteins - chylomicrons in the intestinal mucosa (section 4.3.2.2) and very low-density lipoprotein in the liver (section 5.6.2). 

Triacylglycerols and some phosphoglycerols are synthesized by progressive acylation of glycerol 3-phosphate. The pathway bifurcates at phosphatidate, forming inositol phospholipids and cardiolipin on the one hand and triacylglycerol and choline and ethanolamine phospholipids on the other. 

Triacylglycerol. Triglyceride a compound consisting of three molecules of fatty acids esterified to glycerol. It is a neutral fat synthesized from carbohydrates for storage in animal adipose cells. On enzymatic hydrolysis, it releases free fatty acids in the blood. Tuberculosis. Any of the infectious diseases of man and animals caused by species Mycobacterium and characterized by the formation of tubercles and caseous necrosis in the tissues. 

PA is the precursor of many other phosphoglycerides. The steps in its synthesis from glycerol phosphate and two fatty acyl CoAs were illustrated in Figure 16.14, p. 187, in which PA is shown as a precursor of triacylglycerol. [Note Essentially all cells except mature ery-. throcytes can synthesize phospholipids, whereas triacylglycerol synthesis occurs essentially only in liver, adipose tissue, lactating mammary glands, and intestinal mucosal cells.]... 

Hansen, H.O., Grunnet, I. and Knudsen, J. 1984a. Triacylglycerol synthesis in goat mammary gland. The effect of ATP, Mg2+ and glycerol 3-phosphate on the esterification of fatty acids synthesized de novo. Biochem J. 220, 513-519. 

After a meal, triacylglycerols are stored in adipose cells. They are synthesized from fatty adds (derived by the action of lipoprotein lipase on chylomicrons and VLDL) and from a glycerol moiety (derived from glucose). 

The phosphoglycerides are synthesized by a process similar in its initial steps to triacylglycerol synthesis—glycerol 3-phosphate combines with two fatty acyl CoAs to form phosphatidic acid. 

In a minor alternative pathway, triacylglycerol is synthesized from glycerol-3-phosphate and acyl-CoA by esterification at the 1,2-positions of glycerol, removal of the phosphate group, and esterification at C3 (Chapter 19). 

This reaction is responsible for formation of most of the cholesteryl ester in plasma. The preferred substrate is phosphatidylcholine, which contains an unsaturated fatty acid residue on the 2-carbon of the glycerol moiety. HDL and LDL are the major sources of the phosphatidylcholine and cholesterol. Apo A-I, which is a part of HDL, is a powerful activator of LCAT. Apo C-I has also been implicated as an activator of this enzyme however, activation may depend on the nature of the phospholipid substrate. LCAT is synthesized in the liver. The plasma level of LCAT is higher in males than in females. The enzyme converts excess free cholesterol to cholesteryl ester with the simultaneous conversion of lecithin to lysolecithin. The products are subsequently removed from circulation. Thus, LCAT plays a significant role in the removal of cholesterol and lecithin from the circulation, similar to the role of lipoprotein lipase in the removal of triacylglycerol contained in chylomicrons and VLDL. Since LCAT regulates the levels of free cholesterol, cholesteryl esters, and phosphatidylcholine in plasma, it may play an important role in maintaining normal membrane structure and fluidity in peripheral tissue cells. 

Phosphatidate is formed by successive acylations of glycerol 3-phosphate by acyl Co A. Flydrolysis of its phosphoryl group followed by acylation yields a triacylglycerol. CDP-diacylglycerol, the activated intermediate in the de novo synthesis of several phospholipids, is formed from phosphatidate and CTP. The activated phosphatidyl unit is then transferred to the hydroxyl group of a polar alcohol, such as inositol, to form a phospholipid such as phosphatidylinositol. In mammals, phosphatidylethanolamine is formed by CDP-ethanolamine and diacylglycerol. Phosphatidylethanolamine is methylated by S-adenosylmethionine to form phosphatidylcholine. In mammals, this phosphoglyceride can also be synthesized by a pathway that utilizes dietary choline. CDP-choline is the activated intermediate in this route. 

Most triacylglycerols are synthesized in liver and stored in adipose tissue. Glycerol-3-phosphate is required for de novo synthesis of triacylglycerols in the liver and reassembly of triacylglycerols (storage) in adipose tissue. The condensation product of glycerol-3-phosphate and two acyl-CoAs is phosphatidic acid which is used in phospholipid synthesis. In human triacylglycerols, palmitate is often attached at C-1 and oleate at C-2. 

The double bonds in soybean oil can be converted to reactive monomers (Khot et al., 2001 Wool et al., 2002a,b). These reactive monomers (maleates) are copolymerized with styrene through free radical mechanism to form rigid thermosetting resins. The maleates are obtained by glycerol transesterification of soybean oil followed by esterification with maleic anhydride. Several triacylglycerol-based polymers and composites were synthesized, and their properties compared. 

One of the toxic effects of acetaldehyde is inhibition of tubuhn polymerization. Tubulin is used in the liver for secretion of very low-density lipoprotein (VLDL) particles containing newly synthesized triacylglycerols. As a result, these triacyl-glycerols accumulate in the liver, and he has begun to develop a fatty liver. Acetaldehyde may also damage protein components of the inner mitochondrial membrane and affect its ability to pump protons to the cytosol. 

Very low density lipoprotein (VLDL) is produced in the liver, mainly from dietary carbohydrate. Lipogenesis is an insulin-stimulated process through which glucose is converted to fatty acids, which are subsequently esterified to glycerol to form the triacylglycerols that are packaged in VLDL and secreted from the liver. Thus, chylomicrons primarily transport dietary lipids, and VLDL transports endogenously synthesized lipids. 

Fig. 32.13. Fate of chylomicrons. Chylomicrons are synthesized in intestinal epithelial cells, secreted into the lymph, pass into the blood, and become mature chylomicrons (see Fig. 32.11). On capillary walls in adipose tissue and muscle, lipoprotein lipase (LPL) activated by ApoCn digests the triacylglycerols (TG) of chylomicrons to fatty acids and glycerol. Fatty acids (FA) are oxidized in muscle or stored in adipose cells as triacylglycerols. The remnants of the chylomicrons are taken up by the liver by receptor-mediated endocytosis. Lysosomal enzymes within the hepatocyte digest the remnants, releasing the products into the cytosol.

Gluconeogenic flux from glycerol, synthesis of glycogen, recycling of triacylglycerol, and stimulation of pentose cycle by phenazine metho-sulfate followed. 0 and gave same label distribution in newly synthesized glucose. 

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