Acylglycerol synthesis

The membranes of the endoplasmic reticulum contain the enzyme system for acylglycerol synthesis, and the ribosomes are responsible for protein synthesis. 

Fig. 23.3. Major metabolic routes for long-chain fatty acyl Co As. Fatty acids are activated to acyl CoA compounds for degradation in mitochondrial P-oxidation, or incorporation into triacylglycerols or membrane lipids. When P-oxidation is blocked through an inherited enzyme deficiency, or metabolic regulation, excess fatty acids are diverted into tri-acylglycerol synthesis.

Various other blocking groups are discussed by Buchnea (1978) and Gunstone and Norris (1983) with respect to their use in acylglycerol synthesis. 

Figure 4.14). Once inside, they are esterified into acylglycerols. In discussing the control of acylglycerol synthesis, we shall be discussing the esterification of fatty acids synthesized de novo or released from circulating lipoproteins. The control of fatty acid synthesis itself is discussed in section 3.2.7. 

Fatty acids released by the lipase are transported out of the cell, bound to plasma albumin (section 5.3.5) and transported to those tissues, such as muscle, that utilize fatty acids as major sources of fuel. Whether fatty acids are directed into /3-oxidation or acylglycerol synthesis may be governed by the competition for available acyl-CoA molecules by the acyltransferases involved in the esterification of acylglycerols (section 4.6.2) and the carnitine palmitoyl transferase of the mitochondrial membrane (Figure 4.14... 

The triacylglycerols (Figure 14—6) are esters of the tri-hydric alcohol glycerol and fatty acids. Mono- and di-acylglycerols wherein one or two fatty acids are esteri-fied with glycerol are also found in the tissues. These are of particular significance in the synthesis and hydrolysis of triacylglycerols. 

The intestinal absorption of dietary cholesterol esters occurs only after hydrolysis by sterol esterase steryl-ester acylhydrolase (cholesterol esterase, EC 3.1.1.13) in the presence of taurocholate [113][114], This enzyme is synthesized and secreted by the pancreas. The free cholesterol so produced then diffuses through the lumen to the plasma membrane of the intestinal epithelial cells, where it is re-esterified. The resulting cholesterol esters are then transported into the intestinal lymph [115]. The mechanism of cholesterol reesterification remained unclear until it was shown that cholesterol esterase EC 3.1.1.13 has both bile-salt-independent and bile-salt-dependent cholesterol ester synthetic activities, and that it may catalyze the net synthesis of cholesterol esters under physiological conditions [116-118], It seems that cholesterol esterase can switch between hydrolytic and synthetic activities, controlled by the bile salt and/or proton concentration in the enzyme s microenvironment. Cholesterol esterase is also found in other tissues, e.g., in the liver and testis [119][120], The enzyme is able to catalyze the hydrolysis of acylglycerols and phospholipids at the micellar interface, but also to act as a cholesterol transfer protein in phospholipid vesicles independently of esterase activity [121],... 

Figure 8-1. Hormonal regulation of fat metabolism. A Control of fatty acid synthesis by reversible phosphorylation of acetyl CoA carboxylase. B Regulation of tri-acylglycerol degradation by reversible phosphorylation of hormone-sensitive lipase. cAMP, cyclic adenosine monophosphate HS, hormone-sensitive.

Fig. 21-20 see also Fig. 17-1). Flux through this tri-acylglycerol cycle between adipose tissue and liver may be quite low when other fuels are available and the release of fatty acids from adipose tissue is limited, but as noted above, the proportion of released fatty acids that are reesterified remains roughly constant at 75% under all metabolic conditions. The level of free fatty acids in the blood thus reflects both the rate of release of fatty acids and the balance between the synthesis and breakdown of triacylglycerols in adipose tissue and liver. 

The flow of intermediates through metabolic pathways is controlled by four mechanisms 1) the availability of substrates 2) allosteric activation and inhibition of enzymes 3) covalent modification of enzymes and 4) induction-repression of enzyme synthesis. In the fed state, these regulatory mechanisms ensure that available nutrients are captured as glycogen, tri-acylglycerol, and protein. 

As can be seen in Table 4.2, the fatty acids are not randomly distributed among the three positions of the TG in bovine milk. Control of esterification is not understood, but there are several factors known to affect it. The presence of glucose is known to stimulate the synthesis of milk TG (Dimmena and Emery 1981 Rao and Abraham 1975). In the mouse, Rao and Abraham concluded that glucose was supplying factors other than NADPH or acylglycerol precursors that stimulated milk fat synthesis. The fatty acid that is esterified is known to be affected by the concentration of the acyl donors present (Marshall and Knudsen 1980 Bickerstaffe and Annison 1971). However, in studies under various conditions, palmitic acid was consistently esterified at a greater rate than other fatty acids (Bauman and Davis 1974 Moore and Christie 1978 Smith and Abraham 1975). 

Considerable recent research has defined conditions for successful use of lipases and other enzymes in numerous lipid modification reactions, including a variety of types of interesterifications (69, 71, 76). For edible applications to date, they have been employed at industrial scales for the production of (1) cocoa butter substitutes, for which disaturated, monounsaturated acylglycerols with the unsaturated fatty acid in the sn-2 position are desired (77) (2) to produce human milkfat analogues, where 2-palmitoyl acylglycerols are desired (77) (3) in the synthesis of 1,3- di-acylglycerols (78) and in the production of diacylglycerols for edible applications. These reactions employ vegetable oils as feedstocks. 

Most biodiesel synthesis processes produce a fuel that has a slight contamination with acylglycerols, and this fact is recognized in most current biodiesel standards (Table 1). In spite of their low concentrations, these acylglycerols may contribute disproportionately to fuel lubricity. 

To date, lysophospholipase D (lysoPLD), autotoxin (ATX), phospholipase A1 (PLAl), phospholipase A2 (PLA2), and acylglycerol kinase (AGK) are enzymes reported to be involved in LP synthesis (Chun and Rosen, 2006). There are multiple pathways responsible for LPA production (Meyer zu Heringdorf and Jakobs, 2007). 

The next step in phospholipid biosynthesis is catalyzed by 1-acylglycerol phosphate acyltransferase (the plsC gene product) which acylates the product of the PlsB step to form phosphatidic acid (Fig. 5). Phosphatidic acid comprises only about 0.1% of the total phospholipid in E. coli and turns over rapidly, a property consistent with its role as an intermediate in phospholipid synthesis. The 1-acylglycerol phosphate acyltransferase is thought to transfer unsaturated fatty acids selectively to the 2-position. The plsC gene is universally expressed in bacteria. 

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