Disease relevance of phosphatidylethanolamine

• Upon expression of the bradyrhizobial pmtA gene in Escherichia coli, predominantly monomethylphosphatidylethanolamine was formed from PE [1].
• Phosphatidylethanolamine (PE) was isolated from Bacillus megaterium grown at 20 and 55 degrees C (PE-20 and PE-55) [2].
• This method was applied to the separation of PE isolated from HT29 human colon cancer cells and roughly 30 PE species were resolved [3].
• Fusion between Sendai virus and liposomes containing phosphatidylethanolamine (PE) and different mole fractions of ganglioside GD1a has been investigated [4].
• In both M.9.1.1 and hepatoma cells transfected with PSS2 cDNA the rate of synthesis of PtdSer and PtdSer-derived PtdEtn did not exceed that in parental CHO cells or control McArdle cells respectively, in contrast to cells expressing similar levels of murine PSS1 [5].

High impact information on phosphatidylethanolamine

• Most notably, the plasma membrane is enriched in saturated species of PS and PE [6].
• In situ hybridization in E11.5 embryos showed that Pcyt1a is expressed ubiquitously, with the highest level in fetal liver, and CCTalpha transcripts are significantly more abundant than transcripts encoding CCTbeta or phosphatidylethanolamine (PtdEtn) N-methyl transferase, two other enzymes capable of producing PtdCho [7].
• Reduction of the CCTalpha transcripts in heterozygous E11.5 embryos was accompanied by upregulation of CCTbeta and PtdEtn N-methyltransferase transcripts [7].
• Moreover, elimination of PE production in mitochondria causes fragmented, misshapen mitochondria, an abnormality that likely contributes to the embryonic lethality [8].
• In the yeast Saccharomyces cerevisiae, the primary route for the biosynthesis of PC consists of three consecutive methylation steps of phosphatidylethanolamine (PE) catalyzed by the phospholipid N-methyltransferases Cho2p and Opi3p [9].

Biological context of phosphatidylethanolamine

• The combined results indicate that the selective methylation of PE species by the methyltransferases plays an important role in shaping the steady-state profile of PC molecular species in yeast [9].
• Control experiments showed that differences in [3H]PS and -PE molecular species profiles are not due to (i) incorporation of 3H label to some PE species via alternative pathways, (ii) differences in degradation or remodeling among species, or (iii) selective decarboxylation of PS molecular species by the enzyme [10].
• The BK effect was significantly higher in old cells and, very likely, PKC-independent, since phorbol 12-myristate 13-acetate failed to induce PtdEtn hydrolysis [11].
• Late pregnancy in the rat (gestational ages 16-21 days) was accompanied by a specific increase in hepatic phosphatidylcholine (PC) and phosphatidylethanolamine (PE) molecular species containing C16:0 at the sn-1 position and polyunsaturated essential fatty acids (PUFA), in particular C22:6(n-3), at the sn-2 position [12].
• In summary, our results indicate that serum cholesterol and phospholipid fractions (except PE) are increased during hibernation in bears [13].

Anatomical context of phosphatidylethanolamine

• Interestingly, the hydrophilic diacyl molecular species were found to be much more abundant in PE than in PS, suggesting that hydrophilic PS species may be more readily transported to mitochondria than the hydrophobic ones [10].
• In strains with a psd1Delta allele for the mitochondrial PtdSer decarboxylase, the conversion of nascent PtdSer to PtdEtn can serve as an indicator of lipid transport to the locus of PtdSer decarboxylase 2 (Psd2p) in the Golgi/vacuole [14].
• A similar preferential conversion of di-C16:1 PE to PC was found in vitro upon incubating isolated microsomes with S-adenosyl[methyl-D3]methionine [9].
• In addition, the impaired VLDL secretion from the choline-deficient hepatocytes could also be corrected by supplementation of betaine (0.2 mM) and homocysteine (0.2 mM), indicating the utilization of a methyl group from betaine for PC formation via methylation of PE [15].
• In the ROS disk membranes the value for S perpendicular was marginally higher than in the PC membranes, perhaps reflecting the influence of PE [16].

Associations of phosphatidylethanolamine with other chemical compounds

• We have demonstrated that hepatic very low density lipoprotein (VLDL) secretion requires active phosphatidylcholine (PC) synthesis via either the CDP-choline pathway or phosphatidylethanolamine (PE) methylation pathway (Yao, Z., and Vance, D.E. (1988) J. Biol. Chem. 263, 2998-3004) [15].
• Activation of PLD by free radicals was further confirmed by quantitation of ethanolamine released from PE [17].
• Free radical exposure did not alter neutral lipids, but among the phospholipids, phosphatidylethanolamine (PE) content was decreased on exposure to superoxide anion, generated by xanthine-xanthine oxidase or menadione with a concomitant increase in the level of phosphatidic acid (PA), suggesting activation of phospholipase D (PLD) [17].
• Our results reveal that cholesterol induces the formation of a liquid-ordered phase in POPE membranes, similar to those observed for various PC/cholesterol systems [18].
• Both phosphatidylethanolamine (PE) and phosphatidylserine (PS) enhanced the hydrolase activity at pH 6 [19].

Gene context of phosphatidylethanolamine

• Standard phenotypic analyses indicate that inactivation of the phosphatidylethanolamine (PtdEtn) pathway for PtdCho biosynthesis, however, does not rescue the growth and secretory defects associated with Sec14p deficiency [20].
• Furthermore, the concentration of mitochondrial phospholipids such as phosphatidylcholine (PC) and phosphatidylethanolamine (PE) was increased and the content of phosphatidic acid (PA), a product of PLD activity, was up-regulated in the mitochondrial membrane fractions of AD brain compared with that of control brain [21].
• These data suggest that PC, rather than PE and PG, is the major in vivo substrate of PLD alpha [22].
• PS can be decarboxylated to PE, and PC is synthesized from PE by phosphatidylethanolamine N-methyltransferase (PEMT) [23].
• The PE-directed PLD activity is abolished by antibodies against the IL-1 type I receptor and against IL-1 [24].

Analytical, diagnostic and therapeutic context of phosphatidylethanolamine

• The cells were pulse labeled with [3H]serine whereafter the distribution of the labels among PS and PE molecular species was determined by reverse phase high performance liquid chromatography and liquid scintillation counting [10].
• To investigate how these biosynthetic enzymes contribute to the composition of the PC species profile, the precursor-product relationships between PE and newly synthesized PC were determined at the level of the molecular species by using electrospray ionization tandem mass spectrometry and stable isotope labeling [9].
• Ca2(+)-dependent binding of adseverin to PS liposomes but not to PC or PE liposomes was observed by a centrifugation assay [25].
• This conclusion was substantiated by analysing the molecular species by electrospray ionization-mass spectrometry (ESI-MS/MS), which revealed that PE and NaCl-induced PBut share a unique (18 : 1)2-structure [26].
• Using receptor-based microtiter well immunoassays, we observed binding to be equal, specific, and saturable for PE and Gg 4 but low and nonspecific for PS [27].

References