Triacylglycerol hydrolase

The process of triacylglycerol hydrolysis is a complex phenomenon that involves at least three lipases, lipid droplet associated proteins, and FABPs, although other adipocyte lipases (i.e., triacylglycerol hydrolase) may play a role in basal lipolysis. The data at this time support the model that three lipases are the major contributors to adipocyte lipolysis. Complete hydrolysis of triacylglycerol involves the hydrolysis of three ester bonds to liberate three fatty acids and a glycerol moiety. ATGL catalyzes hydrolysis of the first... 

Lipases (triacylglycerol hydrolases, EC 3.1.1.3) are enzymes that catalyze reactions such as hydrolysis, interesterification, esterification, alcoholysis, acidolysis, and aminolysis [1]. There is an increasing interest in the development of lipase applications to oleochemical transformations to obtain esters of long-chain fatty acids, as monoalkyl esters of fatty acids [2]. Utilization of lipase as a catalyst for the production of biodiesel, defined as a mixture of monoalkyl esters, is a clean technology due to its nontoxic and environmental fnendly nature, requiring mild operating conditions compared with chemical method [3]. 

Alam, M., Vance, D. E., and Lehner, R. (2002). Structure-function analysis of human triacylglycerol hydrolase by siic-directed mutagenesis identification of the catalytic triad and a glycosy-lation site, Biocfiemistry 41, 6679-6687. 

Dolinsky, V. W., Sipione, S, Lehner, R and Vance, D. E. (2001), The cloning and expression of a murine triacylglycerol hydrolase cDNA and the structure of iLs corresponding gene. BiocMm. Biophys. Acta 15J2, 162-172,... 

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],... 

Lipases (triacylglycerol acyl hydrolases, EC 3.1.1.3), have been well established as a valuable catalyst in organic synthesis.12 They are usually distinguished from carboxyl esterases (EC 3.1.1.1) by their substrate spectra, i.e. esterases prefer water soluble substrates and lipases show significantly higher activity towards their natural substrates,... 

Fig. 2. Targeted lipidomics of 2-AG metabolism. Postulated pathways for 2-AG metabolism. Abbreviations PLC, phospholipase C DAG, diacylglycerol DGL, diacylglycerol lipase MGL, monoacylglycerol lipase PLA, phospholipase A AT, acyltransferase TAGL, triacylglycerol lipase PIP2, phosphatidylinositol bisphosphate ABHD-6/12 hydrolase lyso-PL, lysophospholipid lyso-PA, lysophosphatidic acid PA, phosphatidic add P, phosphatase COX, cydooxygen-ase LOX, lipoxygenase CYP450, cytochrome P450 CDP, cytidine diphosphate.

During natural evolution, a broad variety of enzymes has been developed, which are classified according to the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (IUBMB). Thus, for each type of characterized enzyme an EC (Enzyme Commission) number has been provided (see http // www.expasy.ch/enzyme/). For instance, all hydrolases have EC number 3 and further subdivisions are provided by three additional digits, e.g. all lipases (official name triacylglycerol lipases) have the EC number 3.1.1.3 and are thus distinguished from esterases (official name carboxyl esterases) having the EC number 3.1.1.1. This classification is based on the substrate (and cofactor) specificity of an enzyme only, however often very similar amino acid sequences and also related three-dimensional structures can be observed. 

Lipases are ester hydrolases acting on triacylglycerols. They achieve their highest catalytic rate at oil-water interfaces. Though they widely differ in size, substrate and catalytic rate and show little sequence similarity, the Ser...His...Asp(Glu) triad in the active site is a structural feature common to serine proteases (cf. Section 3.1.1.) and lipases. Their mechanism of action is not yet fully revealed. X-ray diffraction studies suggest that the putative hydrolytic site is covered by a surface loop and is therefore inaccessible to solvent (Brady et al., 1990 Winkler et al., 1990). Therefore the enzyme... 

This enzyme (triacylglycerol acyl-hydrolase) has a molecular mass of approximately 42 kDa (Hide, Chan, and Li 1992) and a short half-life of about 1-3 h in dogs. Pancreatic lipase is secreted in its active form, and this activity is enhanced by colipase and bile salts the enzyme hydrolyzes triglycerides to monoglycerides. Other lipases— phospholipase a, phospholipase b, and cholesterol ester hydrolase—are also secreted by the pancreas. 

The breakdown of triacylglycerol is catalysed by lipases. A large number of such enzymes have been purified from animals, plants and microbes (cf. Brockerhoff and Jensen, 1974). It should be noted that the term lipase is frequently misused. A true lipase is one which attacks triacylglycerols and acts only at an oil-water interface. This definition therefore excludes enzymes acting on water-soluble esters (esterases) or those preferentially hydrolysing other lipids (acyl hydrolases). 

Although bacteria do not store energy as triacylglycerol, a number of bacterial lipases have been discovered and studied. An extensive review of microbial lipases (and esterases) has been made by Lawrence (1967). It should be emphasized also that many of the microbial Upases (e.g. the widely studied Rhizopus arrhizus enzyme) are, in fact, acyl hydrolases. 

Enzymes that attack mono- and diacylglycerols, but not triacylglycerols, are well known in animal tissues. However, Brockerhoff and Jensen (1974) point out that these are unlikely to be specific enzymes, and their action can be explained as being due to esterase or nonspecific acyl hydrolase activities. 

True lipases from plants will hydrolyze these partial glycerides, but other enzymes that attack monoacylglycerols (but not triacylglycerols) have been described. However, in most cases the full substrate specificities of these enzymes have not been studied. In one case a lipolytic acyl hydrolase from potato tubers was shown to hydrolyze mono- and diacylglycerols in addition to a range of polar lipids. Thus, to avoid introducing a class of hydrolytic... 

---