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PubMed2001

Plasmalogens: workhorse lipids of membranes in normal and injured neurons and glia.

Plasmalogens are unique glycerophospholipids because they have an enol ether double bond at the sn-1 position of the glycerol backbone. They are found in all mammalian tissues, with ethanolamine plasmalogens 10-fold higher than choline plasmalogens except in muscles. The enol ether double bond at the sn-1 position makes plasmalogens more susceptible to oxidative stress than the corresponding ester-bonded glycerophospholipids. Plasmalogens are not only structural membrane components and a reservoir for second messengers but may also be involved in membrane fusion, ion transport, and cholesterol efflux. Plasmalogens may also act as antioxidants, thus protecting cells from oxidative stress. Receptor-mediated degradation of plasmalogens by plasmalogen-selective phospholipase A2 results in the generation of arachidonic acid, eicosanoids, and platelet activating factor. Low levels of these metabolites have trophic effects, but at high concentration they are cytotoxic and may be involved in allergic response, inflammation, and trauma. Levels of plasmalogens are decreased in several neurological disorders including Alzheimer's disease, ischemia, and spinal cord trauma. This may be due to the stimulation of plasmalogen-selective phospholipase A2. A deficiency of plasmalogens in peroxisomal disorders and Niemann-Pick type C disease indicates that this deficiency may be due to the decreased activity of plasmalogen synthesizing enzymes that occur in peroxisomes.

Alzheimer Disease↗
PubMed1996

Plasmalogen phospholipids in plasma lipoproteins of normolipidemic donors and patients with hypercholesterolemia treated by LDL apheresis.

Recent evidence indicates that plasmalogen phospholipids are particularly sensitive to oxidation and may possess antioxidative properties. Approximately 4.4%-5.5% of phosphatidylcholine (PC), and 53%-60% of phosphatidylethanolamine (PE) consisted of the plasmalogen phospholipids, plasmenylcholine and plasmenylethanolamine, respectively, in whole plasma, low density lipoprotein (LDL) and high density lipoprotein (HDL) of 11 normolipidemic donors. Of total plasmalogen phospholipids in plasma, slightly more was associated with LDL particles (about 42%) than with HDL (36%). Plasmalogen phospholipid levels were analyzed in 12 patients with familial hypercholesterolemia (FH) regularly treated by LDL apheresis, of whom 6 were supplemented with vitamin E (alpha tocopherol, 400 IU/day), the remaining 6 not receiving the antioxidant. Before apheresis (pre), total plasmalogen phospholipid levels in plasma and LDL (expressed as mumol/mmol cholesterol of compartment) decreased as follows: patients receiving vitamin E > normolipidemia > patients not receiving vitamin E. In both hypercholesterolemic groups, the contents of plasmalogen phospholipids in whole plasma and LDL were 3-5-fold higher than those of vitamin E. Directly after apheresis (post), plasmalogen phospholipid levels in plasma were raised by about 50% in the two hypercholesterolemic groups, mostly due to increases in plasmenylethanolamine levels. Two days after apheresis (48 h post), plasmalogen contents were still elevated in plasma and red blood cell membranes of patients receiving vitamin E, while they had already reached pre-apheresis values in those not supplemented with alpha tocopherol. Molecular species of plasma diacyl phospholipids containing polyunsaturated fatty acids were elevated at pre in patients receiving vitamin E as compared to patients without supplementation. At 48 h post, LDL apheresis induced an increase in these molecular species only in patients receiving vitamin E. In conclusion, the contents of plasmalogen phospholipids in plasma lipoproteins are at least three times higher than those of vitamin E. LDL apheresis raises the level of plasmalogen phospholipids in plasma, the increase persisting longer in patients supplemented with vitamin E. Supplementation with vitamin E appears to protect plasmalogen phospholipids in plasma lipoproteins against oxidative degradation.

Adult↗
PubMed1992

Polyunsaturated fatty acid incorporation into plasmalogens in plasma membrane of glioma cells is preceded temporally by acylation in microsomes.

Plasmalogens (1-O-alk-1'-enyl-2-acyl-sn-glycero-3-phosphoethanolamine) are major phospholipids in many tissues and cells, particularly of neural origin. Using cultured C6 glioma cells and subcellular fractions isolated on Percoll gradients we investigated selectivity for esterification of several polyunsaturated fatty acids (PUFA) in the sn-2 position of plasmalogens compared to [1-14C]hexadecanol, representative of de novo synthesis of the ether-linked sn-1 position. In whole cells at a final concentration of 105 microM PUFA, 2-4 nmol plasmalogen/mg protein was labeled in 4 h and 10-14 nmol in 24 h, representing 8-15% and 35-50%, respectively, of initial plasmalogen mass. Incorporation of label from hexadecanol was lower than PUFA incorporation (20:5(n-3) greater than 20:4(n-6) greater than 18:3(n-3) much greater than 18:2(n-6)) suggesting deacylation-reacylation at the sn-2 position. Plasmalogens accounted for 50% of total cell ethanolamine phospholipids and 75% in plasma membrane. Using a novel, improved method for extraction of subcellular fractions containing Percoll, plasma membrane also was enriched in plasmalogen relative to microsomes (107.4 +/- 5.2 vs. 40.0 +/- 2.9 nmol/mg protein). Selectivity for esterification at the sn-2 position of plasmalogens with respect to chain length and unsaturation of the fatty acyl chain was similar in both subcellular fractions and reflected that of whole cells. Labeling of plasma membrane with PUFA and fatty alcohol lagged behind that of microsomes. Chase experiments in cells prelabeled with [1-14C]18:3(n-3) for 2 h showed no significant reduction of label in plasmalogen of any subcellular fraction although accumulation of label in the microsomal fraction was slowed initially. Reduction of plasmalogen label (40-50%) did occur in microsomes and plasma membrane when cells prelabeled for 24 h were switched to chase medium with or without chase fatty acid. Our data suggest that esterification of PUFA to plasmalogen may occur at the endoplasmic reticulum with subsequent translocation to plasma membrane resulting in accumulation of relatively stable pools of plasmalogen that are not readily accessible for deacylation-reacylation exchange with newly appearing PUFA. Alternatively, deacylation-reacylation may occur in a more stable phospholipid pool within the plasma membrane but would involve a slower process than at the endoplasmic reticulum.

Acylation↗
PubMed1991

Synthesis of phosphatidylethanolamine and ethanolamine plasmalogen by the CDP-ethanolamine and decarboxylase pathways in rat heart, kidney and liver.

Studies with mammalian cell lines have led to suggestions that mammalian tissues may derive all of their phosphatidylethanolamine (PE) from the decarboxylation of phosphatidylserine (PS), and also that the physiological significance of the CDP-ethanolamine pathway was the synthesis of ethanolamine plasmalogen. We have therefore investigated the biosynthesis of PE and ethanolamine plasmalogen via the CDP-ethanolamine and decarboxylation pathways in vivo in three rat tissues (heart, kidney and liver), which differ in ethanolamine plasmalogen content. In all three tissues [14C]ethanolamine was incorporated into both PE and ethanolamine plasmalogen, whereas [3H]serine was incorporated into only PS and PE fractions. When [14C]ethanolamine was introduced into the animals, the specific radioactivity of ethanolamine plasmalogen in the kidney was always greater than that of the PE fraction; in the heart the specific radioactivity of the ethanolamine plasmalogen fraction was similar to that of the PE fraction, whereas in the liver the specific radioactivity of the PE fraction was always greater than that of the ethanolamine plasmalogen fraction. The results obtained in this study indicate that: (1) the CDP-ethanolamine pathway is utilized for the synthesis of both PE and ethanolamine plasmalogen in all three tissues; (2) the decarboxylation pathway is utilized solely for the synthesis of PE; (3) serine plasmalogens are not formed by base-exchange reactions; (4) the relative utilization of the CDP-ethanolamine pathway for the synthesis of PE and ethanolamine plasmalogen varies among tissues. Our studies also revealed that the hypolipidaemic drug MDL 29350 is a potent inhibitor of PE N-methyltransferase activity in vitro and in vivo.

Animals↗
PubMed1991

Differential turnover of polyunsaturated fatty acids in plasmalogen and diacyl glycerophospholipids of isolated cardiac myocytes.

To investigate the relative turnover of esterified polyunsaturated fatty acids in diacylglycerophospholipids and plasmalogens in isolated cardiac myocytes, we characterized the phospholipid composition and distribution of radiolabel in different phospholipid classes and in individual molecular species of diradyl choline (CGP) and ethanolamine (EGP) glycerophospholipids after incubation of isolated cardiac myocytes with [3H]arachidonate or [14C]linoleate. Plasmalogens in CGP (55%) and EGP (42%) quantitatively accounted for the total plasmalogen content (39%) of cardiac myocyte phospholipids. Plasmalogens comprised 86% and 51% of total arachidonylated CGP and EGP mass, respectively, and [3H]arachidonate was primarily incorporated into plasmalogens in both CGP (65%) and EGP (61%) classes. The specificity activity of [3H]arachidonylated diacyl-CGP was approximately 2- to 5-fold greater than that of [3H]arachidonylated choline plasmalogen, whereas comparable specific activities were found in the [3H]arachidonate-labeled ethanolamine plasmalogen and diacyl-EGP pools. Of the total linoleate-containing CGP and EGP mass, 54% and 57%, respectively, was esterified to plasmalogen molecular species. However, [14C]linoleate was almost exclusively incorporated into diacyl-CGP (96%) and diacyl-EGP (86%). The specific activities of [14C]linoleate-labeled diacyl-CGP and diacyl-EGP were 5- to 20-fold greater than that of the [14C]linoleate-labeled plasmalogen pools. The differential incorporation of polyunsaturated fatty acids in plasmalogens and diacylglycerophospholipids demonstrates that the metabolism of the sn-2 fatty acyl moiety in these phospholipid subclasses is differentially regulated, possibly fulfilling separate and distinct physiologic roles.

Animals↗
PubMed1990

Incorporation of polyunsaturated fatty acids into plasmalogens, compared to other phospholipids of cultured glioma cells, is more dependent on chain length than on selectivity between (n - 3) and (n - 6) families.

In several tissues and cells, polyunsaturated fatty acids (PUFA) are esterified to plasmalogens (1-O-alk-1'-enyl-2-acyl-sn-glycero-3 phosphoethanolamine). Some studies have implicated selectivity for (n - 3) fatty acids, particularly of 20- and 22-carbons, over the (n - 6) family of fatty acids. We have investigated selectivity for esterification of both families of PUFA to plasmalogens in cultured C6 glioma cells. By 24 h, approx. 40% of cell-associated label from [1-14C]18:3(n - 3) was incorporated into plasmalogens and that label consisted almost exclusively of desaturation and chain elongation products [80% 20:5(n - 3) and 15% 22:5(n - 3)]. Relative incorporation of label from PUFA into plasmalogens was 20:5(n - 3) greater than 20:4(n - 6) greater than 18:3(n - 3) much greater than 18:2(n - 6); incorporation of unaltered 18-carbon chains was highly restricted. Cells incubated with [1-14C]18:3(n - 3) and 20-150 microM competing unlabeled fatty acids showed 20:5(n - 3) greater than 20:4(n - 6) greater than or equal to 22:4(n - 6) greater than 18:3(n - 3) as inhibitors of plasmalogen labeling. Chase experiments in cells prelabeled with [1-14C]18:3(n - 3) for 2 h showed limited reduction of label in plasmalogen. Reduction of plasmalogen label did occur when (n - 3) or (n - 6) fatty acids were added to cells prelabeled for 48 h, accounting for losses of 20-35% compared to controls. Accordingly, little selectivity occurs in esterification of plasmalogens from mixtures of (n - 3) and (n - 6) fatty acyl chains. Subsequent remodeling of (n - 3) acyl chains occurs, but is more dependent on acyl chain length than on selectivity between (n - 3) and (n - 6) families. Our data are consistent with a stable plasmalogen pool enriched in PUFA, but not specifically with (n - 3) fatty acids.

Binding, Competitive↗
PubMed1998

Isolation of a Chinese hamster fibroblast variant defective in dihydroxyacetonephosphate acyltransferase activity and plasmalogen biosynthesis: use of a novel two-step selection protocol.

We have developed a two-step selection protocol to generate a population of Chinese hamster ovary (CHO) cell variants that are plasmalogen-deficient, but contain intact, functional peroxisomes (plasmalogen-/peroxisome+). This involved sequential exposures of a mutagenized cell population to photodynamic damage by using two different pyrene-labelled sensors, 9-(1'-pyrene)nonanol and 12-(1'-pyrene)dodecanoic acid. By this procedure we generated several isolates, all except one of which displayed a severe decrease in plasmalogen biosynthesis. Further characterization of one of the plasmalogen-deficient isolates, NRel-4, showed that it contained intact, functional peroxisomes. Whole-cell homogenates from NRel-4 displayed severely decreased dihydroxyacetone phosphate acyltransferase, which catalyses the first step in plasmalogen biosynthesis. NRel-4 and another, recently described, plasmalogen-deficient cell line, NZel-1 [Nagan, Hajra, Das, Moser, Moser, Lazarow, Purdue and Zoeller (1997) Proc. Natl. Acad. Sci. U.S. A. 94, 4475-4480] were hypersensitive to singlet oxygen, supporting the notion of plasmalogens as radical oxygen scavengers. Wild-type-like resistance could be conferred on NRel-4 upon restoration of plasmalogen content by supplementation with a bypass compound, sn-1-hexadecylglycerol. NRel-4 and other plasmalogen-/peroxisome+ strains will allow us to examine further the role of ether lipids in cellular functions without complications associated with peroxisome deficiency, and might serve as an animal cell model for certain forms of the human genetic disorder rhizomelic chondrodysplasia punctata.

Acyltransferases↗
PubMed2004

Plasmalogens: targets for oxidants and major lipophilic antioxidants.

Cellular membranes and plasma lipoproteins are less efficiently protected against oxidative stress than the various aqueous compartments of mammalian organisms. Here, previous results on the role of plasmalogens in lipid oxidation are evaluated on the basis of criteria required for an antioxidant. The plasmalogen-specific enol ether double bond is targeted by a vast variety of oxidants, including peroxyl radicals, metal ions, singlet oxygen and halogenating species. Oxidation of the vinyl ether markedly prevents the oxidation of highly polyunsaturated fatty acids, and products of plasmalogen degradation do not propagate lipid oxidation. This protection is also demonstrated intramolecularly, thus ascertaining the function of plasmalogens as a major storage pool for polyunsaturated fatty acids. Although cells rapidly incorporate and synthesize plasmalogens de novo, their plasmalogen contents can be deliberately increased by supplementation with precursors. Thus plasmalogens terminate lipid-oxidation processes, are present in adequate locations at sufficient concentrations, and are rapidly regenerated, classifying them as efficient antioxidants in vitro. Future work should address the in vivo role of plasmalogens in lipid oxidation and the biological function of plasmalogen interactions with oxidants.

Animals↗
PubMed2003

Lymphatic absorption of plasmalogen in rats.

Plasmalogen is a subclass of phospholipids that is widely distributed in man and animals. Many physiological roles have been proposed for this lipid; however, there have been no reports on the intestinal absorption of plasmalogen. In the present study, we examined lymphatic absorption of plasmalogen after the duodenal infusion of emulsified brain phospholipids (BPL) containing plasmalogen (22 mol % of total phospholipids) and soyabean lecithin (SPL) (100 g emulsified phospholipid/l). Male Wistar rats with implanted cannulas in the mesenteric lymph duct and the duodenum were kept in a Bollman-type restraining cage, and were infused the emulsion after 1 d recovery with duodenal infusion of a glucose-NaCl solution. Lymphatic plasmalogen output was increased at 2-4 h after the switch to BPL emulsion, and peaked at 4-6 h. However, no increases were observed after SPL infusion. Lymphatic recovery of plasmalogen for 8 h was 198 nmol, which was 0.22 mol % of the total plasmalogen disappeared from the intestine. We did not detect any increases in long-chain fatty aldehydes, which are the degradation product of plasmalogen, either in the blood or the small intestine. We conclude that a small percentage but a significant amount of the plasmalogen was absorbed into the lymph.

Animals↗
PubMed1984

Deficiency of plasmalogens in the cerebro-hepato-renal (Zellweger) syndrome.

We have analyzed the phospholipid composition of various organs of patients with the cerebro-hepato-renal (Zellweger) syndrome. The phospholipid composition of tissues from controls and patients was very similar except for their plasmalogen contents. In controls about 50% of the phosphatidylethanolamine fraction of brain, heart, kidney and skeletal muscle and about 10% of that fraction in control liver tissue was found to consist of plasmalogen. In control heart muscle, but not in other control tissues about 25% of the phosphatidylcholine fraction consist of plasmalogens. In contrast, plasmalogens were nearly absent in the corresponding tissues of Zellweger patients. The amount of phosphatidylethanolamine plasmalogens in both erythrocytes and fibroblasts of Zellweger patients is lowered significantly compared to control erythrocytes and control fibroblasts respectively, although this reduction is not as dramatic as in brain, heart, kidney, skeletal muscle and liver of patients. Phosphatidylcholine-plasmalogens are only present in low amounts in both controls, heterozygotes and patients. In recent years considerable evidence has accumulated to show that peroxisomes are involved in cellular lipid metabolism. Notably, the key enzymes of ether lipid (plasmalogen) biosynthesis in rodents were recently found to be located in peroxisomes. Since electronmicroscopic studies have shown that peroxisomes are absent in liver and kidney of patients with the cerebro-hepato-renal syndrome, our results suggest that an inability to integrate these key enzymes in a functional peroxisome leads to a severe disturbance in plasmalogen biosynthesis. We propose that the multiple clinical and biochemical defects in Zellweger patients are secondary to a deficiency in peroxisomal function.

Brain Diseases↗
PubMed1994

Serine and ethanolamine incorporation into different plasmalogen pools: subcellular analyses of phosphoglyceride synthesis in cultured glioma cells.

In cultured glioma cells, plasma membrane (PM) is enriched in phosphatidylserine (PtdSer) and plasmalogens (1-O-alk-1'-enyl-2-acyl-sn-glycero-3-phosphoethanolamine). Serine can be a precursor of headgroups of both PtdSer and ethanolamine phosphoglycerides (PE) including plasmalogens and non-plasmalogen PE (NP-PE). Synthesis of phospholipids was investigated at the subcellular level using established fractionation procedures and incorporation of [3H(G)]L-serine and [1,2-14C]ethanolamine. Specific radioactivity of PtdSer from [3H]serine was 2-fold greater in PM than in microsomes, reaching maximum by 2-4 h. Labeled plasmalogen from [3H]serine appeared in PM by 4 h and increased to 48 h, whereas almost no plasmalogen accumulated in microsomes within 12 h. In contrast, labeled plasmalogen from [1,2-14C]ethanolamine appeared in both PM and microsomes at early incubation times and became enriched in PM beyond 12 h. Thus, in glioma cells: (1) greater and faster accumulation of labeled PtdSer in PM may reflect direct synthesis from serine within PM; (2) PM is a major source of PtdSer for decarboxylation and PE synthesis; (3) NP-PE in both PM and microsome provides headgroup for synthesis of plasmalogen; and, (4) plasmalogen synthesis may involve different intracellular pools depending on headgroup origin.

Animals↗
PubMed2004

Determination of choline and ethanolamine plasmalogens in human plasma by HPLC using radioactive triiodide (1-) ion (125I3-).

For the purpose of developing highly sensitive and convenient determination of plasmalogens, the high-performance liquid chromatography (HPLC) method using radioactive iodine ((125)I) was investigated. Radioactive triiodide (1-) ion ((125)I(3)(-)), which is an actual iodine form capable of reacting with vinyl ether bond ([bond]CH(2)[bond]O[bond]CH[double bond]CH[bond]) of plasmalogens, could be safely and efficiently produced by oxidizing a commercial radioactive sodium iodine (Na(125)I) with hydrogen peroxide (H(2)O(2)) under acid condition (pH 5.5-6.0), which is called iodine-125 reagent. I(3)(-) specifically reacted with plasmalogens at the molar ratio of 1:1 in methanol, and 1 or 2 mol of plasmalogens was involved in the binding with iodine per iodine atom, resulting in the formation of stable iodine-binding phospholipids. The HPLC system with Diol column and acetonitrile/water as a mobile phase was available for separating iodine-binding phospholipids from nonbinding free iodine and for separately eluting iodine-binding phospholipids derived from choline and ethanolamine plasmalogens. Using iodine-125 reagent (1.85 MBq/ml), plasmalogens were detectable at high sensitivity of 10,000-15,000 cpm/nmol, which is more than 1000-fold higher sensitivity than the classical determination with nonradioactive iodine. Plasmalogen concentrations in human plasma were measured with the HPLC system and determined as, on average, 129.1+/-31.3 microM (n=8) in a 1.2 content ratio of choline to ethanolamine plasmalogens, a concentration that nearly agrees with the value reported previously.

Choline↗
PubMed1997

Dramatic increase of alpha-hydroxyaldehydes derived from plasmalogens in the aged human brain.

Plasmalogens-substantial compounds of brain tissue--suffer degradation either by hydrolysis under production of aldehydes or by oxidation with lipid peroxylradicals by generation of plasmalogen epoxides. The latter react by addition of pentafluorobenzylhydroxylamine HCl (PFBHA HCL) under hydrolysis to alpha-hydroxyaldehydes which are immediately transformed to pentafluorobenzyloximes (PFBO). Likewise, free aldehydes are transformed to PFBO-derivatives. PFBO-derivatives of free aldehydes and PFBO-derivatives of alpha-hydroxyaldehydes were extracted and after trimethylsilylation quantified by GC/FID and by GC/MSD. The remaining aqueous phase, containing plasmalogens besides other lipids, was hydrolyzed by treatment with acid. The hydrolysis products of plasmalogens, long chain aldehydes, react with PFBHA HCl to produce PFBO-derivatives. These were also quantified by GC/FID. This method allows the quantification of plasmalogens, free aldehydes and plasmalogenepoxides in human brain samples to study changes in the relation of these compounds with increasing age. While the ratio of plasmalogens in respect to derived aldehydes seems to remain constant during life time, the quotient of plasmalogenepoxides to plasmalogens increases with age, indicating that lipid peroxidation processes are involved in the damage of plasmalogens in the brain of aged individuals, starting at an age of about 70 years.

Adolescent↗
PubMed1999

Inhibition of peroxyl radical-mediated lipid oxidation by plasmalogen phospholipids and alpha-tocopherol.

The recently discovered peroxyl radical scavenging properties of plasmalogen phospholipids led us to evaluate their potential interactions with alpha-tocopherol. The oxidative decay of plasmalogen phospholipids and of polyunsaturated fatty acids as induced by peroxyl radicals (generated from 2,2'-azobis-2-amidinopropane hydrochloride; AAPH) was studied in micelles using 1H-NMR and chemical analyses. In comparison with alpha-tocopherol, a 20- to 25-fold higher concentration of plasmalogen phospholipids was needed to induce a similar inhibition of peroxyl radical-mediated oxidation of polyunsaturated fatty acids. Plasmalogen phospholipids and alpha-tocopherol protected each other from oxidative degradation. In low-density lipoproteins (LDL) and micelles supplemented with plasmalogen phospholipids plus alpha-tocopherol, the peroxyl radical-promoted oxidation was additively diminished. The differences in the capacities to inhibit oxidation processes induced by peroxyl radicals between the plasmalogen phospholipids and alpha-tocopherol were less pronounced in the LDL particles than in the micelles. In conclusion, plasmalogen phospholipids and alpha-tocopherol apparently compete for the interaction with the peroxyl radicals. Oxidation processes induced by peroxyl radicals are inhibited in an additive manner in the presence of the two radical scavengers. The contribution of the plasmalogen phospholipids to the protection against peroxyl radical promoted oxidation in vivo is expected to be at least as important as that of alpha-tocopherol.

Amidines↗
PubMed1998

Plasmalogens effectively reduce the surface tension of surfactant-like phospholipid mixtures.

The alkenyl-acyl subclass of phosphatidylethanolamine (PtdEtn) and phosphatidylcholine (plasmalogens) are minor components of alveolar surfactant. Plasmalogens promote and stabilize hexagonal structures of phospholipids. In another study (W.R. Perkins, R.B. Dause, R.A. Parente, S.R. Michey, K.C. Neuman, S.M. Gruner, T.F. Taraschi, and A.S. Janoff. Science 273: 330-332, 1996), it was shown that polymorphic phase behavior may have an important role in the effective functioning of pulmonary surfactant. Therefore, we hypothesized that surface properties of phospholipid mixtures that contain plasmalogens are superior to plasmalogen-free mixtures. The effect of plasmalogens on surface tension of surfactant-like phospholipid mixtures (70 mol% dipalmitoyl phosphatidylcholine, 10 mol% phosphatidylglycerol, and 20 mol% PtdEtn) was measured. Using the pulsating bubble surfactometer, we show that an increasing amount of ethanolamine plasmalogens [plasmenylethanolamine (PlsEtn) results in reduction of surface tension (0 mol% PlsEtn 44.7 +/- 1.7, 2 mol% 33.5 +/- 1.7, 4 mol% 36 +/- 3.1, 6 mol% 26.2 +/- 2.9, and 8 mol% 22.2 +/- 0.3 mN/m). By means of the captive bubble surfactometer, minimal surface tension reached with 8 mol% PlsEtn was even lower (3.8 +/- 0.7 mN/m). With regard to morphological studies (B. Fringes, K. Gorgas, and A. Reith. Eur. J. Cell Biol. 46: 136-143, 1988), clofibrate treatment of rats might increase the plasmalogen content of alveolar surfactant. However, in the present study, we could not show that synthesis and secretion of plasmalogens are affected by clofibrate treatment.

1,2-Dipalmitoylphosphatidylcholine↗
PubMedDate not supplied

Plasmalogens, phospholipase A2, and docosahexaenoic acid turnover in brain tissue.

Plasmalogens are glycerophospholipids of neural membranes containing vinyl ether bonds. Their synthetic pathway is located in peroxisomes and endoplasmic reticulum. The rate-limiting enzymes are in the peroxisomes and are induced by docosahexaenoic acid (DHA). Plasmalogens often contain arachidonic acid (AA) or DHA at the sn-2 position of the glycerol moiety. The receptor-mediated hydrolysis of plasmalogens by cytosolic plasmalogen-selective phospholipase A2 generates AA or DHA and lysoplasmalogens. AA is metabolized to eicosanoids. The mechanism of signaling with DHA is not known. The plasmalogen-selective phospholipase A2 differs from other intracellular phospholipases A2 in molecular mass, kinetic properties, substrate specificity, and response to glycosaminoglycans, gangliosides, and sialoglycoproteins. A major portion of [3H]DHA incorporated into neural membranes is found at the sn-2 position of ethanolamine glycerophospholipids. Studies with a mutant cell line defective in plasmalogen biosynthesis indicate that the incorporation of DHA is reduced in this RAW 264.7 cell line by 50%. In contrast, the incorporation of AA remains unaffected. This is reversed completely when the growth medium is supplemented with sn-1-hexadecylglycerol, suggesting that DHA can be selectively targeted for incorporation into plasmalogens. We suggest that deficiencies of DHA and plasmalogens in peroxisomal disorders, Alzheimer's disease (AD), depression, and attention deficit hyperactivity disorders (ADHD) may be responsible for abnormal signal transduction associated with learning disability, cognitive deficit, and visual dysfunction. These abnormalities in the signal-transduction process can be partially corrected by supplementation with a diet enriched with DHA.

Animals↗
PubMed1988

Plasmalogen biosynthesis in peroxisomal disorders: fatty alcohol versus alkylglycerol precursors.

In recent years a growing number of inherited diseases have been recognized to originate from an impairment in one or more peroxisomal functions. Since it is well established that the first two steps in the biosynthesis of plasmalogens proceed in peroxisomes, we studied the biosynthesis of plasmalogens in cultured skin fibroblasts from patients with different peroxisomal and related disorders. When de novo plasmalogen biosynthesis was studied by growing the cells in the presence of [14C]hexadecanol, impaired plasmalogen biosynthesis was found in rhizomelic chondrodysplasia punctata, cerebrohepatorenal (Zellweger) syndrome, neonatal adrenoleukodystrophy, and infantile Refsum disease. In all these cases, alkyl-acyl phospholipids, the precursors of plasmalogens, did not accumulate and 1-O-[9,10-3H2]octadecylglycerol was converted into plasmalogens with equal efficiency as in controls. This indicated that impaired de novo plasmalogen biosynthesis as measured by [14C]hexadecanol incorporation was due to a deficient formation of the glycero-ether bond. Using this procedure, normal de novo plasmalogen biosynthesis was found in X-linked adrenoleukodystrophy, adrenomyeloneuropathy, X-linked chondrodysplasia punctata, adult Refsum disease, as well as in heterozygotes for Zellweger syndrome and infantile Refsum disease. The data have indicated that the average extent of the deficiency in glycero-ether bond formation is different in Zellweger syndrome, chondrodysplasia punctata, neonatal adrenoleukodystrophy, and infantile Refsum disease.

Cells, Cultured↗
PubMed1993

Identification of a lysophospholipase C that may be responsible for the biosynthesis of choline plasmalogens by Madin-Darby canine kidney cells.

The biosynthesis of choline plasmalogens was investigated in Madin-Darby canine kidney cells to determine the source of the vinyl ether linkage. 1-O-[3H] Alk-1'-enyl-2-lyso-sn-glycero-3-phosphoethanolamine was a better precursor than 1-O-[3H]alkyl-2-lyso-sn-glycero-3-phosphocholine for the synthesis of 1-O-[3H]alk-1'-enyl-2-acyl-sn-glycero-3-phosphocholine; this suggests that the vinyl ether linkage in choline phosphoglycerides originates from ethanolamine plasmalogens. The contribution of N-methylation and base exchange enzymes to choline plasmalogen biosynthesis was assessed using 1-O-[3H]alkenyl-2-lyso-sn-glycero-3-[32P]phosphoethanolamine. While 1-O-[3H]alkenyl-2-acyl-sn-glycero-3-phosphocholine was formed from this precursor, the 32P was lost indicating that N-methylation and base exchange enzymes do not contribute significantly to the synthesis of choline plasmalogens. The conversion of a phosphono analog of 1-O-[3H]alkyl-2-lyso-sn-glycero-3-phosphoethanolamine, which is resistant to phospholipase D hydrolysis, to 1-O-[3H]alkenyl-2-acyl-sn-glycero-2-phosphocholine was observed demonstrating that phospholipase D is not required for choline plasmalogen biosynthesis. A Mg(2+)-dependent lysophospholipase C activity was detected in microsomes that actively hydrolyzed ether-linked lysophosphoglycerides as well as the lysophosphono analog. To assess the role of lysophospholipase C in shuttling 1-O-alk-1'-enyl-sn-glycerol (alkenylglycerol) from ethanolamine plasmalogens to choline plasmalogens, cells prelabeled with 1-O-[3H]alkenyl-2-lyso-sn-glycero-3-phosphoethanolamine were treated with 12-O-tetradecanoylphorbol-13-acetate. This resulted in the rapid deacylation of 1-O-[3H]alkenyl-2-acyl-sn-glycero-3-phosphoethanolamine to 1-O-[3H]alkenyl-2-lyso-sn-glycero-3-phosphoethanolamine and the subsequent generation of 1-O-[3H]alkenylglycerol. A concomitant 2-3-fold increase in 1-O-[3H]alkenyl-2-acyl-sn-glycero-3-phosphocholine was observed. These studies suggest that the alkenyl linkage in choline phosphoglycerides may originate from 1-O-alkenyl-2-lyso-sn-glycero-3-phosphoethanolamine through an enzymatic pathway involving lysophospholipase C to generate alkenylglycerol that is subsequently converted to choline plasmalogens.

Animals↗