Cephalin synthesis

Baer, E. and Buchnea, D. (1959) Synthesis of L-a-(dioleoyl)-cephalin, with a comment on the stereochemical designation of glycerol phosphatides,./. Am. Chem. 

The reagent is useful for the synthesis of a-glycerylphosphorylethanolamine (4), a moiety of cephalin and plasmalogens. D-Acetone glycerol (1) is phosphorylated... 

Phosphatidylethanolamines, or cephalins (so-called because they were first obtained from brain tissue), can be synthesized by reactions analogous to those of de novo synthesis of phosphatidylcholine. Ethanolamine is first phosphorylated by ATP and ethanolamine kinase to phosphoethanolamine, which then reacts with CTP to form CDP-ethanolamine. CTPrphosphoethanolamine cytidylyltransferase is not located on the endoplasmic reticulum, nor do fatty acids activate it as they do the analogous enzyme of phosphatidylcholine synthesis. Finally, 1,2-diacylglycerol phosphoethanolamine transferase catalyses the reaction of diacylglycerol with CDP-ethanolamine to form phosphatidylethanolamine. 

Baer and Stanacev (1964) have reported the synthesis of dipalmitoyl L-a-glyceryl (2-aminoethyl) phosphonate, the first synthesis of a complex lipid containing phosphonic acid, and have shown spectra of L-a-(dipalmitoyl)cephalin and of dipalmitoyl L-a-phosphono(deoxy)cephalin. 

This report described the synthesis of diether phosphonolipids which resemble cephalins structurally. Infrared spectra were given for dihexadecanoyl L-a-glyceryl-(-2-aminoethyl) phosphonate and dihexadecanoyl L-a-glycerylphosphorylethanola-mine. 

This subject has been extensively studied in the case of the lecithins (phosphatidylcholines) and it has been shown that, in the presence of certain enzymes of different specificity, the same mechanism is responsible for the synthesis of cephalins (phosphatidylethanolamines). As with the formation of glycerides, the starting point is a phosphatidic acid. The... 

Both the a,/3-diglyceride and the phosphatidic acid may be used for the synthesis of phospholipids. The choline and ethanolamine required respectively for the synthesis of lecithins and cephalins must be available in an active form as their cytidine diphosphate derivatives. 

The above considerations lead to the conclusion that the liver should be capable of synthesizing plasma phospholipides in toto from its various components. This appears to be the case, for a purified enzyme preparar-tion of rat liver has been shown to form diacylphosphatidic acids from fatty acids and L-a-glycerophosphate. i The diacylphosphatidic acids need only a nitrogenous base in ester linkage with the phosphate to form lecithin (or a cephalin). The following mechanism was postulated for the synthesis of distearylphosphatidic acid from stearic acid-l-C and L-o-glycerophosphate-P (a-G-P) by the rat liver preparation ... 

Phospholipides.— Lecithin and other phospholipides of the diet are important nutritional somces of choUne and of phosphoric acid, and are resolved into their components by the esterases of the small intestine previous to absorption. Within the intestinal mucosa, a re-synthesis occiun, or a new phospholipide is assembled containing units derived from the saponified fats of the diet, and as such participates in the lipide transport in the lymph and the portal blood. By use of a phosphate containing a radioactive isotope of phosphorus as indicator, Artom and his colleagues (1937) have shown that phospholipides of the lecithin and cephalin type are synthesised in large quantities during fat absorption, and accumulate in the intestinal mucosa, the liver, and to a lesser extent, the kidney, but not in the spleen, heart or skeletal muscles. 

The path of conversion of inorganic phosphate to phosphatide is not known. Glycerophosphate, diglycerides, neutral fat, choline phosphate, phosphoproteins, or other compounds may be involved as intermediates. That aminoethylphosphoric acid can be excluded from this group of substances follows from the work of Chargaff and Keston (38). Experiments in which 80 mg. of labeled disodium aminoethyl phosphate was administered to adult rats by subcutaneous injection showed that the body was unable to utilize aminoethylphosphoric acid as such for the synthesis of cephalin. Of the administered as aminoethylphosphoric acid, 28% was found to be excreted through the kidneys in the course of eight hours in these experiments. 

Enzymic hydrolysis of aminoethylphosphoric acid in the tissues is presumably followed by utilization of the inorganic phosphate for synthesis of lecithin and of demethylation of lecithin to form cephalin. The aminoethylphosphoric acid normally occurring in the body tissue may be a product of catabolism of cephalin. 

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