Fatty acylated, selectively

Synthesis of a Fatty Acylated, Selectively Deprotected Disaccha-ride... 

Figure 6. Initial phase ofsynthesis of a fatty acylated, selectively deprotected disaccharide. Key to formulas same as for Figure I.

Constantinides, P. R, and J. M. Steim. 1988. Micellization of fatty acyl-CoA mixtures and its relevance to the fatty acyl selectivity of acyltransferase rch. Biochem. Biophy 61 430-436. 

Selected entries from Methods in Enzymology [vol, page(s)] Absorption maxima of disulfide bond, 251, 55 fatty acylation of... 

Selected entries from Methods in Enzymology [vol, page(s)] Application in fluorescence, 240, 734, 736, 757 convolution, 240, 490-491 in NMR [discrete transform, 239, 319-322 inverse transform, 239, 208, 259 multinuclear multidimensional NMR, 239, 71-73 shift theorem, 239, 210 time-domain shape functions, 239, 208-209] FT infrared spectroscopy [iron-coordinated CO, in difference spectrum of photolyzed carbonmonoxymyo-globin, 232, 186-187 for fatty acyl ester determination in small cell samples, 233, 311-313 myoglobin conformational substrates, 232, 186-187]. 

A simple approach for lipidation of peptides with di-fatty acid substituted glycerol moieties is based on the use of glyceric acid.119" For this purpose (2i )-glyceric acid is esterified at the two hydroxy groups with fatty acid acyl chlorides and the resulting lipophilic synthon (18) is used directly as an active ester, e.g. Pfp ester, to acylate selected amino groups of peptides, or is used to acylate suitably functionalized spacers. 

A very consistent chracteristic is the selective positioning of the fatty acyl residues on the glycerol backbone. Thus, in a very large percentage of the naturally ocurring phosphatidylcholines, the hydrocarbon chains on the C-l position are highly saturated—hence little or no olefinic bonds are present. On the other hand, when the acyl residues on C-2 are analyzed, well over 95%... 

Specificity is one of the most striking properties of enzyme molecules. Enzyme specificity can be defined as a comparative difference in rates of catalysis of certain reactions. After an enzyme is identified as a hpase, several specificities within the class are identified or can be expected to occur. The main advantage of lipases, which differentiate enzymatic reactions from chemically-catalyzed reactions, is lipase specificity. Lipases have turned out to be very useful enzymes for catalyzing various types of reactions with a rather wide substrate specificity. The fatty acid specificity of lipases has been exploited to produce structured lipids and to enrich lipids with specific fatty acids to improve the nutritional characteristics of lipids (24). Certain lipases display positional specificity (regiospecificity) toward fatty acyl groups in a TAG molecule as well as fatty acid selectivity. 

Additional complexity occurs at the level of the starter and extender units used for constructing the polyketide scaffold, where the typically 2-4 carbon building blocks such as acetyl-, malonyl-, and propionyl-CoA are selectively used by different PKSs, thus increasing the repertoire of potential products formed. For example, results obtained from work with plant enzymes have shown that larger and more complex starter units such as phenylpropanoid- as well as fatty acyl-CoAs can also serve as efficient substrates (22,23,24). 

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. 

After consumption of usual food fats, the major products of digestion that are absorbed are 2 in-MG and FFA. In the small intestinal cells, the sn-2-MG react with activated FFA to be converted by a multienzyme complex into TG. The excess FFA react with sn-3-glycerophosphate to form lysophospha-tidic acids, which are further converted into phosphatidic acids. Dephosphorylation results in ot-1, 2-DG, which are precursors of both TG and PL. What happens after the influx of sn-l,3-DG or sn-l(3)-MG into the intestinal cell is less clear. A series of competing reactions must be considered, such as complete digestion, acylation, transacylation, phosphorylation, and intact excretion out of the intestinal cells as well. Lipases are present in the intestinal cells but their action seems to be reduced by other intestinal cell constituents (28). The sn-1,2-DG seem to be poor substrates for intestinal TG synthesis (29), whereas in-l-MG can be phosphorylated into lysophosphatidic acid (30) and possibly be metabolized fur-dier as described above. It has to be realized, however, that j -3-glycerophosphate acyltransferase possesses fatty acid selectively, incorporating mainly palmitic acid at the sn-1... 

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