Phosphatidylethanolamine action

Lysophospholipids have been found in butter serum by Cho et al. (1977). They characterized the sn-1 and -2 lysophosphatidylcholines and phosphatidylethanolamines. It is not known if these compounds are products of degradation or remnants of biosynthesis. Cho et al. (1977) searched for, but did not find, another possible product of enzymatic degradation of milk, phosphatidic acid. Phosphatidic acid can be formed by the action of phospholipase D on phosphatidylcholine, for example, but this enzymatic activity was not detected. The compound is also an important intermediate in the biosynthesis of lipids, but the concentration in tissue is always very low. The amount is also low in milk. Cho et al. (1977) found 1.2 and 0.9 (percent of total lipid P) of the lyso compounds above. The quantities of the other phospholipids were phosphatidylethanolamine, 27.3 -choline, 29.1 -serine, 13.4 -inositol, 2.5 and sphingomyelin, 25.6. 

The remainder of the radioactivity is associated with three main phospholipid classes, namely, phosphatidylcholine, phosphatidylethanolamine, and the phosphoinositides, mainly PIP2. Nonetheless, this type of result is commonly attributed to the action of a phospholipase A2, which is activated upon agonist interaction with the platelet. The other presumed product, a lysolecithin, would not be labeled in the above experimental protocol and thus, due to the very small amount formed in the reaction, could not be detected. Though one could potentially label the polar head group of the parent phosphoglycerides, there is little need to do so since the arachidonic acid is associated almost exclusively with the sn-2 ester position on phosphoglycerides. Consequently, the release of free arachidonic acid can be safely attributed to phospholipase A2 activity. While the yield of arachidonic acid is very low, the activation of the cell occurs only over a short time span, anywhere from 5 sec to 1 min. Thus self-control of cell activation is evident. 

Phospholipase A2 Action. As in the case of phosphatidylcholine, the above-mentioned phospholipases will attack only the sn-3 form of naturally occurring (as well as synthetic) phosphatidylethanolamine. The products are, of course, lysophosphatidylethanolamine (1 -6>-acyl-2-lyso-.rn-glycero-3-phosphoethanolamine) and the fatty acids (liberated from the sn-2 position). The latter can be analyzed for composition and structure, as the methyl esters, by gas-liquid chromatography coupled with mass spectrometry. Usually these acyl groups are largely the unsaturated types. 

Phosphatidylethanolamines can also be synthesized by decarboxylation of phosphatidylserine and in mammals principally through action of the Ca -mediated base exchange enzyme (Figure 19-3). Phosphatidylserine production in liver occurs at the cytosolic face of the endoplasmic reticulum. In brain tissue, this phospholipid accounts for up to 15% of the total phospholipid content. 

Kakiki et ai. (1969) reported that EBP inhibited the incorporation of glucosamine-into the cell wall of Piricularia orysae. This suggested that a mode of action of this compound might be the inhibition of chitin biosynthesis. According to the experiments of Akatsuka et al. (1977) and of Kodama et al. (1979) the specific inhibition of conversion from phosphatidylethanolamine to phos-phatidylcholin by the transmethylation of S-adenosylmethionine might be one of the modes of action of IBP. 

Although phosphatidylserine is in general asymmetrically distributed in cell membranes with the bulk of this lipid in the cytoplasmic leaflet of the bilayer, some phosphatidylserine appears to reside in the outer lipid monolayer of the axonal membrane. Furthermore, this phosphatidylserine is involved in the nerve action potential. Treatment of an axon with extracellular serine decarboxylase converts phosphatidylserine to -ethanolamine, which results in a decrease in the action potential spike height. Catalysis of the reversed reaction by this enzyme in the presence of excess L-serine converts phosphatidylethanolamine to -serine. This produces an average of 28% increase in the action potential amplitude. It is worth noticing that several anaesthetic compounds have been shown to bind phosphatidylserine in vitroThe role of phosphatidylserine phase behavior in the nerve action potential will be discussed in somewhat more detail in Section 7. 

HPLC is the most common technique applied to the determination of the chemical composition of lecithin. Normal phase HPLC is convenient for the determination of the major constituents (i.e., phosphatidylcholine, phosphatidylethanolamine, etc), as described in Chapter 7. P NMR is also suitable for this analysis, as discussed in Chapter 14. The biochemical literature contains many enzymatic methods, mainly for specific determination of phosphatidylcholine and its hydrolysis product, choline (32). For instance, phosphatidylcholine can be hydrolyzed by phospholipase C to a diacylglycerol and the phosphate ester of choline, which itself can be hydrolyzed by alkaline phosphatase to form choline and phosphate ion. Alternatively, action of phospholipase D on phosphatidylcholine yields phosphatidic acid and choline. These methods are not applied to analysis of the commercial lecithin used as a surfactant. 

Phosphatidylethanolamine can also be formed by an analogous series of reactions to phosphatidylcholine that is by the successive actions of ethanolamine kinase, ethanolamine phosphate cytidylyltransferase and ethanolamine phosphotransferase (Figure 7.1). As in the synthesis of phosphatidylcholine, the activity of the cytidyltransferase appears to be rate limiting for phosphatidylethanolamine synthesis and also the final enzyme, the ethanolamine phosphotransferase, catalyses a freely reversible reaction. 

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