Diacylglycerol scheme

Figure 11-9 Scheme showing synthesis and release of diacylglycerol and inositol phosphates and their regulation of calcium concentration in response to hormonal stimulation. 

Two pathways from the activated receptor are shown. At the left is activation of phospholipase Cy and formation, at a membrane-bound site, of inositol trisphosphate and diacylglycerol (DAG). The main pathway, in the center, activates Ras with the aid of the G protein Sos. Activated Ras, in turn, activates Raf and successive components of the MAPK cascade. At the right a seven-helix receptor activates both phospholipase C(3 and Ras via interaction with a (3y subunit. (B) A generalized scheme for the MAP kinase pathway. See Seger and Krebs.380... 

Two of the more studied effector proteins of G-proteins are adenylate cyclase (AC) and phospholipase C (PLC). AC converts adenosine triphosphate (ATP, 5.4) into 3, 5 -cyclic adenosine monophosphate (cAMP, 5.5) (Scheme 5.4). cAMP is a secondary messenger that can activate certain kinases (phosphorylation enzymes) and stimulate the breakdown of fats and glycogen. PLC hydrolyzes phosphatidylinositol 3,4-bisphosphate (PIP2, 5.6) to form two secondary messengers, diacylglycerol (DAG, 5.7) and inositol... 

The two-step chemoenzymatic approach starting from glycerol to synthesize the symmetric MLM-type structured TAGs is illustrated in the scheme in Figure 24.2. In the first step lipase regioselectivity was exploited to synthesize symmetric 1,3-diacylglycerols (DAGs) of the MCFA. This was followed by chemical introduction of the PUFA into the mid-position. 

Lewis acid-mediated cleavage of p-methoxybenzyl ethers is much easier than benzyl ethers because of the additional resonance stabilisation afforded by the methoxy group in the p-methoxybenzyl carbocation. Consequently, p-methoxybenzyl ethers can be removed from sensitive substrates as in the final step of a synthesis of the anti-HIV-1 sulfolipid 186.2 [Scheme 4.186] wherein three p-methoxybenzyl ethers were expelled on treatment with excess iodotrimethyl-silane.342 Similarly, a synthesis of 1,2-diacylglycerols 187.2 [Scheme 4.187]343... 

Although not shown in the following simplified scheme, the phospatidic acid/ 1,2-diacylglycerol duo is also an intermediate in the pathway to the phospholipids (phosphatidylcholines, phosphatidylethanolamines, phosphatidylinositols, phospha-tidylinositols, and phosphatidylserines) and the mono- and digalactosyldiacylgly-cerols. 

In this process, an oil (triacylglycerol, also known as triglyceride) molecule reacts with a molecule of water, releasing a molecule of fatty acid (12), commonly known as free fatty acid (FFA), and a molecule of diacylglycerol (DG, also called diglyceride). The reaction scheme is shown below ... 

Supercritical CO2 column fractionation of soybean (57, 86, 88, 89) and rice bran oil (57) deodorizer distillates has been investigated to enrich their sterol and tocopherol contents. Brunner et al. (89) reported that the FFA were enriched in the top (in the extract), whereas the monoacylglycerols, tocopherols, and diacylglycerols were enriched in the bottom (in the raffinate) fraction during the fractionation of soybean oil deodorizer distillate. Saure and Brunner (88) achieved a tocopherol concentration of more than 70% (w/w) using continuous column fractionation of soybean deodorizer distillate where squalene was almost completely found in the top product, whereas sterols and tocopherols were enriched in the bottom product. King and Dunford (57) developed a two-step column fractionation scheme (13.6 MPa and 27.2 MPa at 313 K) for the enrichment of phytosterols from soybean and rice bran oil deodorizer distillates such that the FFA were removed in the first step and sterols were enriched in the oil fraction in the second step. 

Figure 2.12. A scheme for the indirect potentiation of cyclic AMP accumulation elicited by H, -receptor stimulation. Activation ofH,-receptors leads to the production of an intracellular second messenger (e.g., Ca2 + ions or diacylglycerol, DG) which subsequently acts on adenylate cyclase (AC) or phosphodiesterase (PDE) to amplify the cyclic AMP response to agonists acting on receptors directly coupled...

The same group further extended this chemistry to prepare lactones 40 and 41, and also used a modified approach towards other diacylglycerol (DAG) analogues 44 and 45. This latter approach involved synthesis of the spirocyclic lactone intermediate 43 by addition of a Grignard maganesium alkoxide to 42 and the PCC oxidation (Scheme 7). ... 

Figure 12.19 Simplified scheme of the pancreatic hydrolysis of structured lipids (top 1,3-diacylglycerols bottom human milk fat replacers).

A 17-step synthesis of the rigid e-lactone diacylglycerol analogue, (5R, 6S)-5-0-tetradecanoyl-6-hydroxymethyl-6-heptanolide 86, has been reported, starting from L-xylose and proceeding via L-2-deoxyribofuranoside 85 (Scheme 22). ... 

Scheme 5.32. SynthesUi of a constrained diacylglycerol analogue from v-xylose.

Fig. 1. Two alternative schemes proposed to explain the stimulated breakdown and labelling of PI. Abbreviations PA, phosphatidate 1,2-DG, 1,2-diacylglycerol P-CMP, CDP-diacylglycerol.

Thus it would appear that there is no existing experimental information which is incompatible with the view that a primary event brought about stimuli is the removal of the phosphorylinositol group of PI to release diacylglycerol, which then has a short lifetime (probably seconds rather than minutes) before being phosphorylated to phosphatidate. There are, however, a number of facts which are incompatible with the alternative proposal that simply envisages a cyclic interconversion of PI and phosphatidate. Obviously, one can add to the latter model a phosphatidate/diacylglycerol cyclic in ter conversion (bracketed in Scheme 2 of Fig. 1) and thus accomodate additional experimental data satisfactorily, but there is at present... 

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