Synthesis of Triacylglycerols

Fatty acyl-CoA is the donor of the fatty acyl group to the two nonphosphorylated positions of glycerol phosphate to make a phos-phatidic acid. 

The third fatty acid can be added after the removal of the phosphate of the phosphatidic acid. This scheme results in a triacylglyc-erol, although other phosphatidic acids can be used as precursors to various membrane lipids. 

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A synthesis of triacylglycerols has been described that begins with the substance shown... 

Phospholipids may be regarded as derivatives of phos-phatidic acid (Figure 14-8), in which the phosphate is esterified with the —OH of a suitable alcohol. Phos-phatidic acid is important as an intermediate in the synthesis of triacylglycerols as well as phosphoglycerols but is not found in any great quantity in tissues. 

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.

Thioesters play a paramount biochemical role in the metabolism of fatty acids and lipids. Indeed, fatty acyl-coenzyme A thioesters are pivotal in fatty acid anabolism and catabolism, in protein acylation, and in the synthesis of triacylglycerols, phospholipids and cholesterol esters [145], It is in these reactions that the peculiar reactivity of thioesters is of such significance. Many hydrolases, and mainly mitochondrial thiolester hydrolases (EC 3.1.2), are able to cleave thioesters. In addition, cholinesterases and carboxylesterases show some activity, but this is not a constant property of these enzymes since, for example, carboxylesterases from human monocytes were found to be inactive toward some endogenous thioesters [35] [146], In contrast, allococaine benzoyl thioester was found to be a good substrate of pig liver esterase, human and mouse butyrylcholinesterase, and mouse acetylcholinesterase [147],... 

Figure 4.10 Monoacylglycerol pathway for synthesis of triacylglycerol and formation of chylomicrons within the enterocyte.

FIGURE 21-21 Glyceroneogenesis. The pathway is essentially an abbreviated version of gluconeogenesis, from pyruvate to dihydroxyacetone phosphate (DHAP), followed by conversion of DHAP to glycerol 3-phosphate, which is used for the synthesis of triacylglycerol. 

Fatty acids are carried to tissues for use in synthesis of triacylglycerols, phospholipids, and other membrane lipids. The mobilization of fatty acids from triacylglycerol stores and from cholesterol esters depends upon hormone-sensitive lipase (p. 635).53b/ 53c This enzyme is activated by cAMP-dependent phos-... 

The synthesis of triacylglycerol takes place in the endoplasmic reticulum (ER). In liver and adipose tissue, fatty adds in the cytosol obtained from the diet or from de novo synthesis of palmitic add become inserted into the ER membrane. The reactions are shown in Fig. 13-10. Membrane-bound acyl-CoA synthetase activates two fatty acids, and membrane-bound acyl-CoA transferase esterifies them with glycerol 3-phosphate, to form phosphatidic acid. Phosphatidic acid phosphatase releases phosphate, and in the membrane, 1,2-diacylglycerol is esterified with a third molecule of fatty acid. 

Fig. 13-10 The synthesis of triacylglycerol in the endoplasmic reticulum of liver and fat cells.

Phosphatidylcholine, a major phospholipid constituent of membranes and lipoproteins, is synthesized de novo in liver cells. The synthesis occurs on the ER and is linked, through 1,2-diacylglycerol, with the synthesis of triacylglycerol. Three compounds specifically involved in the synthesis of phosphatidylcholine are ... 

The stimulation of phosphatidic acid phosphatase by ethanol stimulates the production of diacylglycerol which in turn stimulates the synthesis of triacylglycerol. Therefore, the triacylglycerol concentration increases in the liver cells. 

Triacylglycerols (Eigure 5.4) consist of a glycerol backbone to which three fatty acids are esterified (Ri.Ra.Rs). Eatty acids are stored as triacylglycerol in all cells, but primarily in adipocytes of adipose tissue. The fatty acids in triacylglycerols are predominantly saturated. The major building block for the synthesis of triacylglycerols, in tissues other than adipose,... 

The pathways diverge at phosphatidate. In the synthesis of triacylglycerols, phosphatidate is hydrolyzed by a specific phosphatase to give a diacylglycerol (DAG). This intermediate is acylated to a triacylglycerol in a reaction that is catalyzed by diglyceride acyltransferase. Both enzymes are associated in a triacylglycerol synthetase complex that is bound to the endoplasmic reticulum membrane. 

Synthesis of triacylglycerols from carbohydrate occurs in the liver in the... 

Figure 6-8. Synthesis of triacylglycerols in liver, adipose tissue, and intestinal cells. R = fatty acyl moiety. VLDL = very-low-density-lipoprotein.

Which of the following is involved in the synthesis of triacylglycerols in adipose tissue ... 

On the other hand, flavonoids without side chains such as quercetin (43), naringenin (69), hesperetin (70), and kaempferol (106) did not inhibit the enzyme activity at a final concentration of 800 xM. These results suggest that the lavandulyl side chain and the position of the hydroxy group might be important for the high DGAT inhibitory activity. Kurarinone (13) also inhibited de novo synthesis of triacylglycerol (TG) in Raji cells (Fig. 31) [22,33]. 

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