Diacylglycerol triacylglycerol synthesis

S Cases, S J Smith, Y-W Zheng, HM Myers, SR Lear, E Sande, S Novak, C Collins, CB Welch, AJ Lusis, SK Erickson, RV Farese Jr. Identification of a gene encoding an acyl CoA diacylglycerol acyltransferase, a key enzyme in triacylglycerol synthesis. Proc Natl Acad Sci (USA) 95 13018-13023, 1998. 

Methyl groups arc utilized in the de novo synthesis of phosphatidylcholine, a process that decreases the availability of 1,2-diacylglycerol for triacylglycerol synthesis. 

Lung, S.C. R.J. Weselake. Diacylglycerol acyltransferase a key mediator of plant triacylglycerol synthesis. Lipids 2QQ6, 41, 1073-1088. 

Ichihara, K., T. Takahashi, and S. Fujii. 1988. Diacylglycerol acyltransferase in maturing safflower seeds its influences on the fatty acid composition of triacyglycerol and on the rate of triacylglycerol synthesis. Biochim. Biophys. Acta 958 125-129. 

He, X., Chen, G.Q., Lin, J.-T, McKeon, T.A., 2006. Diacylglycerol acyltransferase activity and triacylglycerol synthesis in germinating castor seed cotyledons. Lipids 41, 281-285. 

The pathways for the synthesis of phosphoglycerides and triacylglycerol are identical up to the formation of diacylg-lycerol, after which they diverge. Hence there is an important branch-point at diacylglycerol (Figure 11.20). 

Figure 11.20 Diacylglycerol as a branch point in the synthesis of phosphoglycerides and triacylglycerol.

The energy state of the cell dictates the relative rates of phosphatidylcholine, phosphatidylethanolamine, and triacylglycerol biosynthesis. When energy is in short supply, the level of cAMP rises leading to inhibition of fatty acid biosynthesis (see chapter 18). This in turn decreases the supply of diacylglycerol, which limits the synthesis of phosphatidylcholine, phosphatidylethanolamine, and triacylglycerol. When sufficient diacylglycerol is pres-... 

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. 

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 de novo synthesis of phosphatidylcholine requires choline. In liver, phosphatidylcholine is synthesized and enters the membranes and lipoproteins. The dc novo synthesis of phosphatidylcholine also requires 1,2-diacylglycerol. If there is insufficient choline available, phosphatidylcholine production by the de novo pathway cannot occur. The 1,2-diacylglycerol is then converted to triacylglycerol. which accumulates, as it is not secreted in lipoproteins, by the liver. Therefore, the liver cells fill with triacylglycerol. 

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. 

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. 

Phosphatidate is formed by successive acylations of glycerol 3-phosphate by acyl CoA. Hydrolysis of its phosphoiyl group followed by acyl- ation yields a triacylglycerol. CDP-diacylglycerol, the activated intermediate in the de novo synthesis of several phosphoglycerides, is formed from phosphatidate and CTP. The activated phosphatidyl unit is then transferred to the hydroxyl group of a polar alcohol, such as serine, to form a phospholipid such as phosphatidyl serine. 

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