Monoacylglycerol acyltransferase

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). 

TAG content in vegetative tissue has also been increased throngh the introduction of a monoacylglycerol (MAG) pathway into a transient expression system in N. benthamiana leaves, which involves the utilization of MAG for biosynthesis of DAG (Petrie et al., 2012 Divi et al., 2014). Heterologous expression of two forms of mouse (Mus muse ulus) MONOACYLGLYCEROL ACYLTRANSFERASE resulted in DAG production, which in turn increased TAG content in the leaf. TAG increases of 9.2-fold and 7.3-fold were observed for the expression of MGATl and MGAT2, respectively (Petrie et al., 2012). 

Divi, U.K., El Tahchy, A., Vanhercke, T., Petrie, J.R., Robles-Martinez, J.A., Singh, S.P., 2014. Transcriptional and biochemical responses of monoacylglycerol acyltransferase-mediated oil synthesis and associated senescence-Uke responses in Nicotiana benthamiana. Eront. Plant Sci. 5 Article 204. 

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.

Figure 12.1 Some of the processes contributing to plasma lipoprotein metabolism. Abbreviations TG, triacylglycerol FFA, unesterified (free) fatty acids MG, monoacylglycerol VLDL , nascent VLDL VLDL, very-low-density lipoprotein HDL , nascent HDL HDL, high-density lipoprotein C, cholesterol LCAT, lecithin cholesterol acyltransferase LPL, lipoprotein lipase HL, hepatic lipase CE, cholesterol ester PL, phospholipid.

LPA can be produced by several enzymatic routes (Figure 4). However, the relative contributions of these to LPA production is not known since specific inhibitors for many of the enzymes involved are not available (Pages et al., 2001). Firstly, de novo biosynthesis of LPA occurs by acylation of glycerol 3-phosphate, catalysed by glycerophosphate acyltransferase, in both the endoplasmic reticulum and mitochondria. Alternatively, LPA can be synthesized by the phosphorylation of monoacylglycerol or, in peroxisomes, by the reduction of acyl dihydroxyacetone phosphate. Subsequently, acylation of LPA by monoacylglycerolphosphate acyltransferase produces the precursor of all glycerophospholipids, phosphatidic acid. The latter can also act as a precursor of LPA synthesis by phospholipase A-catalysed deacylation. 

Lehner, R, Kuksis, A and Itabashi, Y (1993) Stereospecificity of monoacylglycerol and diacylglycerol acyltransferases from rat intestine as determined by chiral phase high-performance liquid chromatography. Lipids, 28, 29-34. 

Yang, W, Pollard, M., Li-Beisson, Y, Beisson, F., Feig, M., Ohlrogge, J., 2010. A distinct type of glycerol-3-phosphate acyltransferase with sn-2 preference and phosphatase activity producing 2-monoacylglycerol. Proc. Natl. Acad. Sci. U. S. A. 107, 12040-12045. 

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