Plasmalogens account for the major portion of the ethanolamine glycerophospholipids in the adult human brain (50%), but the brain of newborn babies has low levels (7% of total phospholipids mass) (Horrocks and Sharma, 1982). Levels of ethanolamine plasmalogen (PlsEtn) increase rapidly during the intense period of myelination and ethanolamine glycerophospholipids of myelin sheath contain up to 70% PlsEtn. An eight-fold increase in PlsEtn levels per gram of brain tissue occurs in white matter during first year of life so that PlsEtn accounts for 20% of the glycerophospholipid mass and 70% of the ethanolamine glycerophospholipids (Balakrishnan et al., 1961). At that time, myelination is rapid. The highest level of myelin is between 30 and 40 years of age (Toews and Horrocks, 1976). In human brain, there is a steep rise in PlsEtn content, followed by a further rise up to 30–40 years of age. This is followed by a decline of PlsEtn levels during normal aging. At 70 years of age, the levels of PlsEtn are 18% less than at 40 years of age (Rouser and Yamamoto, 1968; Horrocks et al., 1981). In chicks, there is a marked increase in plasmalogen levels in synaptosomes during the first 3 days after hatching (Getz et al., 1968). Collectively, these studies suggest that plasmalogens are major glycerophospholipids in brain tissue. Their metabolism may be involved in signal transduction processes associated with neural cell functions such as synaptogenesis, myelination, and ion transport (Farooqui and Horrocks, 2001).
Plasmalogens impart membranes with different biophysical properties such as phase transition temperature, bilayer thickness, acyl chain packing free volume, and lateral domain. The perpendicular orientation of the sn-2 acyl chain at the membrane surface and the lack of a carbonyl group at the sn-1 position in plasmalogens affect the hydrophilicity of the head group, resulting in stronger intermolecular hydrogen bonding between the head groups (Lohner, 1996). These properties allow PlsEtns to adopt the inverse hexagonal phase and may be responsible for a different membrane potential compared with other glycerophospholipids (Lohner, 1996). This property affects lipid packing, fluidity, and interaction with neural membrane receptors and ion channels. In cellular membranes and lipoproteins, plasmalogens account for 15–20% and 5% of all phospholipids, respectively (Nagan and Zoeller, 2001; Engelmann et al., 1994). PlsEtn and PlsCho are the two major plasmalogen species found in mammalian cell membranes. In most cells, PlsEtns exceed the choline plasmalogens by 10-fold, with the exception of cardiac and skeletal muscle where choline plasmalogen dominates. The level of plasmalogens in brain tissue depends on the degree of myelination and increases rapidly during myelinogenesis (Horrocks, 1972; Horrocks and Sharma, 1982). Factors that modulate the levels of plasmalogens in neurons, astrocytes, and oligodendrocytes during myelination and aging remain unknown.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Acar N., Gregoire S., Andre A., Juaneda P., Joffre C., Bron A. M., Creuzot-Garcher C. P., and Bretillon L. (2007). Plasmalogens in the retina: In situ hybridization of dihydroxyacetone phosphate acyltransferase (DHAP-AT)–the first enzyme involved in their biosynthesis–and comparative study of retinal and retinal pigment epithelial lipid composition. Exp. Eye Res. 84:143–151.
Aguado B. and Campbell R. D. (1998). Characterization of a human lysophosphatidic acid acyltransferase that is encoded by a gene located in the class III region of the human major histocompatibility complex. J. Biol. Chem. 273:4096–4105.
Albi E., Cataldi S., Magni M. V., and Sartori C. (2004). Plasmalogens in rat liver chromatin: New molecules involved in cell proliferation. J. Cellular Physiol. 201:439–446.
Albi E. and Magni M. P. V. (2004). The role of intranuclear lipids. Biol. Cell. 96:657–667.
André A., Chanséaume E., Dumusois C., Cabaret S., Berdeaux O., and Chardigny J. M. (2006a). Cerebral plasmalogens and aldehydes in senescence-accelerated mice P8 and R1: A comparison between weaned, adult and aged mice. Brain Res. 1085:28–32.
André A., Juanéda P., Sébédio J. L., and Chardigny J. M. (2005a). Effects of aging and dietary n-3 fatty acids on rat brain phospholipids: Focus on plasmalogens. Lipids 40:799–806.
André A., Juanéda P., Sébédio J. L., and Chardigny J. M. (2006b). Plasmalogen metabolism-related enzymes in rat brain during aging: influence of n-3 fatty acid intake. Biochimie 88:103–111.
André A., Tessier C., Brétillon L., Sébédio J. L., and Chardigny J. M. (2005b). In situ hybridization of dihydroxyacetone phosphate acyltransferase, the regulating enzyme involved in plasmalogen biosynthesis. Mol. Brain Res. 136:142–147.
Antony P., Freysz L., Horrocks L. A., and Farooqui A. A. (2003). Ca2+-independent phospholipases A2 and production of arachidonic acid in nuclei of LA-N-1 cell cultures: A specific receptor activation mediated with retinoic acid. Mol. Brain Res. 115:187–195.
Balakrishnan S., Goodman H., and Cumings J. N. (1961). The distribution of phosphorus-containing lipid compounds in the human brain. J. Neurochem. 8:276–284.
Biermann J., Just W. W., Wanders R. J., and van den Bosch H. (1999). Alkyl-dihydroxyacetone phosphate synthase and dihydroxyacetone phosphate acyltransferase form a protein complex in peroxisomes. Eur. J. Biochem. 261:492–499.
Biermann J., Schoonderwoerd K., Hom M. L., Luthjens L. H., and van den Bosch H. (1998). The native molecular size of alkyl-dihydroxyacetonephosphate synthase and dihydroxyacetonephosphate acyltransferase. Biochim. Biophys. Acta 1393:137–142.
Blank M. L., Smith Z. L., Cress E. A., and Snyder F. (1994). Molecular species of ethanolamine plasmalogens and transacylase activity in rat tissues are altered by fish oil diets. Biochim. Biophys. Acta Lipids Lipid Metab. 1214:295–302.
Brites P., Waterham H. R., and Wanders R. J. A. (2004). Functions and biosynthesis of plasmalogens in health and disease. Biochim. Biophys. Acta Mol. Cell Biol. Lipids 1636:219–231.
Brosche T. (2001). Plasmalogen levels in serum from patients with impaired carbohydrate or lipid metabolism and in elderly subjects with normal metabolic values. Arch. Gerontol. Geriatr. 32:283–294.
Cai J., Nelson K. C., Wu M., Sternberg P., Jr., and Jones D. P. (2000). Oxidative damage and protection of the RPE. Prog. Retin. Eye Res. 19:205–221.
Causeret C., Bentejac M., Albet S., Teubner B., and Bugaut M. (1997). Copurification of dihydroxyacetone-phosphate acyl-transferase and other peroxisomal proteins from liver of fenofibrate-treated rats. Biochimie 79:423–433.
Chang L., Ernst T., Poland R. E., and Jenden D. J. (1996). In vivo proton magnetic resonance spectroscopy of the normal aging human brain. Life Sci. 58:2049–2056.
Datta S. C., Ghosh M. K., and Hajra A. K. (1990). Purification and properties of acyl/alkyl dihydroxyacetone-phosphate reductase from guinea pig liver peroxisomes. J. Biol. Chem. 265:8268–8274.
de Vet E. C., Hilkes Y. H., Fraaije M. W., and van den Bosch H. (2000). Alkyl-dihydroxyacetonephosphate synthase. Presence and role of flavin adenine dinucleotide. J. Biol. Chem. 275:6276–6283.
de Vet E. C., IJlst L., Oostheim W., Dekker C., Moser H. W., van den Bosch H., and Wanders R. J. (1999). Ether lipid biosynthesis: Alkyl-dihydroxyacetonephosphate synthase protein deficiency leads to reduced dihydroxyacetonephosphate acyltransferase activities. J. Lipid Res. 40:1998–2003.
de Vet E. C. and van den Bosch H. (2000). Alkyl-dihydroxyacetonephosphate synthase. Cell Biochem. Biophys. 32:117–121.
El Bassiouni E. A., Piantadosi C., and Snyder F. (1975). Metabolism of alkyldihydroxyacetone phosphate in rat brain. Biochim. Biophys. Acta 388:5–11.
Engelmann B., Bräutigam C., and Thiery J. (1994). Plasmalogen phospholipids as potential protectors against lipid peroxidation of low density lipoproteins. Biochem. Biophys. Res. Commun. 204:1235–1242.
Farooqui A. A., Antony P., Ong W. Y., Horrocks L. A., and Freysz L. (2004). Retinoic acid-mediated phospholipase A2 signaling in the nucleus. Brain Res. Rev. 45:179–195.
Farooqui A. A. and Horrocks L. A. (2001). Plasmalogens: Workhorse lipids of membranes in normal and injured neurons and glia. Neuroscientist 7:232–245.
Farooqui A. A. and Horrocks L. A. (2004). Plasmalogens, platelet-activating factor, and other ether lipids. In: Nicolaou A. and Kokotos G. (eds.), Bioactive Lipids. Oily Press, Bridgwater, England, pp. 107–134.
Favrelière S., Stadelmann-Ingrand S., Huguet F., De Javel D., Piriou A., Tallineau C., and Durand G. (2000). Age-related changes in ethanolamine glycerophospholipid fatty acid levels in rat frontal cortex and hippocampus. Neurobiol. Aging 21:653–660.
Fleming P. J. and Hajra A. K. (1977). 1-Alkyl-sn-glycero-3-phosphate:acyl-CoA acyltransferase in rat brain microsomes. J. Biol. Chem. 252:1663–1672.
Getz G. S., Bartley W., Lurie D., and Notton B. M. (1968). The phospholipids of various sheep organs, rat liver and of their subcellular fractions. Biochim. Biophys. Acta 152:325–339.
Ghosh M. K. and Hajra A. K. (1986). Subcellular distribution and properties of acyl/alkyl dihydroxyacetone phosphate reductase in rodent livers. Arch. Biochem. Biophys. 245:523–530.
Hajra A. K., Larkins L. K., Das A. K., Hemati N., Erickson R. L., and MacDougald O. A. (2000). Induction of the peroxisomal glycerolipid-synthesizing enzymes during differentiation of 3T3–L1 adipocytes–Role in triacylglycerol synthesis. J. Biol. Chem. 275:9441–9446.
Hoffman-Kuczynski B. and Reo N. V. (2004). Studies of myo-inositol and plasmalogen metabolism in rat brain. Neurochem. Res. 29:843–855.
Hoffman-Kuczynski B. and Reo N. V. (2005). Administration of myo-inositol plus ethanolamine elevates phosphatidylethanolamine plasmalogen in the rat cerebellum. Neurochem. Res. 30:47–60.
Horrocks L. A. (1972). Content, composition, and metabolism of mammalian and avian lipids that contain ether groups. In: Snyder F. (ed.), Ether Lipids: Chemistry and Biology. Academic Press, New York, pp. 177–272.
Horrocks L. A. and Farooqui A. A. (2004). Docosahexaenoic acid in the diet: Its importance in maintenance and restoration of neural membrane function. Prostaglandins Leukot. Essent. Fatty Acids 70:361–372.
Horrocks L. A. and Sharma M. (1982). Plasmalogens and O-alkyl glycerophospholipids. In: Hawthorne J. N. and Ansell G. B. (eds.), Phospholipids, New Comprehensive Biochemistry, Vol. 4. Elsevier Biomedical Press, Amsterdam, pp. 51–93.
Horrocks L. A., VanRollins M., and Yates A. J. (1981). Lipid changes in the ageing brain. In: Davison A. N. and Thompson R. H. S. (eds.), The Molecular Basis of Neuropathology. Edward Arnold Ltd., London, pp. 601–630.
Horrocks L. A., Yeo Y. K., Harder H. W., Mozzi R., and Goracci G. (1986). Choline plasmalogens, glycerophospholipid methylation, and receptor-mediated activation of adenylate cyclase. In: Greengard P. and Robison G. A. (eds.), Advances in Cyclic Nucleotide and Protein Phosphorylation Research, Vol. 20. Raven Press, New York, pp. 263–292.
Ide H. and Nakazawa Y. (1985). Phosphatidate phosphatase in rat liver: the relationship between the activities with membrane-bound phosphatidate and aqueous dispersion of phosphatidate. J Biochem. 97:45–54.
Jamal Z., Martin A., Gomez-Munoz A., and Brindley D. N. (1991). Plasma membrane fractions from rat liver contain a phosphatidate phosphohydrolase distinct from that in the endoplasmic reticulum and cytosol. J. Biol. Chem. 266:2988–2996.
Jones C. L. and Hajra A. K. (1983). Solubilization and partial purification of dihydroxyacetone-phosphate acyltransferase from guinea pig liver. Arch. Biochem. Biophys. 226:155–165.
Kirschner D. A. and Ganser A. L. (1982). Myelin labeled with mercuric chloride. Asymmetric localization of phosphatidylethanolamine plasmalogen. J. Mol. Biol. 157:635–658.
Kofman O., Agam G., Shapiro J., and Spencer A. (1998). Chronic dietary inositol enhances locomotor activity and brain inositol levels in rats. Psychopharmacology (Berl) 139:239–242.
Korey S. R. and Orchen M. (1959). Plasmalogens of the nervous system. I. Deposition in developing rat brain and incorporation of 14C isotope from acetate and palmitate into the α, β-unsaturated ether chain. Arch. Biochem. Biophys. 83:381–389.
Lee T. C. (1998). Biosynthesis and possible biological functions of plasmalogens. Biochim. Biophys. Acta Lipids Lipid Metab. 1394:129–145.
Liu D. L., Nagan N., Just W. W., Rodemer C., Thai T. P., and Zoeller R. A. (2005). Role of dihydroxyacetonephosphate acyltransferase in the biosynthesis of plasmalogens and nonether glycerolipids. J. Lipid Res. 46:727–735.
Lohner K. (1996). Is the high propensity of ethanolamine plasmalogens to form non-lamellar lipid structures manifested in the properties of biomembranes? Chem. Phys. Lipids 81:167–184.
Mancini A., Del Rosso F., Roberti R., Orvietani P., Coletti L., and Binaglia L. (1999). Purification of ethanolaminephosphotransferase from bovine liver microsomes. Biochim. Biophys. Acta Lipids Lipid Metab. 1437:80–92.
Marinetti G. V. and Crain R. C. (1978). Topology of amino phospholipids in the red cell membrane. J. Supramol. Struct. 8:191–213.
Mozzi R., Gramignani D., Andriamampandry C., Freysz L., and Massarelli R. (1989). Choline plasmalogen synthesis by the methylation pathway in chick neurons in culture. Neurochem. Res. 14:579–583.
Murphy R. C. (2001). Free-radical-induced oxidation of arachidonoyl plasmalogen phospholipids: Antioxidant mechanism and precursor pathway for bioactive eicosanoids. Chem. Res. Toxicol. 14:463–472.
Nagan N., Hajra A. K., Das A. K., Moser H. W., Moser A., Lazarow P., Purdue P. E., and Zoeller R. A. (1997). A fibroblast cell line defective in alkyl-dihydroxyacetone phosphate synthase: a novel defect in plasmalogen biosynthesis. Proc. Natl. Acad. Sci. USA 94:4475–4480.
Nagan N., Hajra A. K., Larkins L. K., Lazarow P., Purdue P. E., Rizzo W. B., and Zoeller R. A. (1998). Isolation of a Chinese hamster fibroblast variant defective in dihydroxyacetonephosphate acyltransferase activity and plasmalogen biosynthesis: Use of a novel two-step selection protocol. Biochem. J. 332:273–279.
Nagan N. and Zoeller R. A. (2001). Plasmalogens: Biosynthesis and functions. Prog. Lipid Res. 40:199–229.
Nonaka M., Kohmura E., Yamashita T., Yamauchi A., Fujinaka T., Yoshimine T., Tohyama M., and Hayakawa T. (1999). Kainic acid-induced seizure upregulates Na+/myo-inositol cotransporter mRNA in rat brain. Brain Res. Mol. Brain Res. 70:179–186.
Ofman R., Hettema E. H., Hogenhout E. M., Caruso U., Muijsers A. O., and Wanders R. J. (1998). Acyl-CoA:dihydroxyacetonephosphate acyltransferase: Cloning of the human cDNA and resolution of the molecular basis in rhizomelic chondrodysplasia punctata type 2. Hum. Mol. Genet. 7:847–853.
Ofman R., Hogenhout E. M., and Wanders R. J. (1999). Identification and characterization of the mouse cDNA encoding acyl-CoA:dihydroxyacetone phosphate acyltransferase. Biochim. Biophys. Acta 1439:89–94.
Ofman R., Lajmir S., and Wanders R. J. A. (2001). Etherphospholipid biosynthesis and dihydroxyactetone-phosphate acyltransferase: Resolution of the genomic organization of the human GNPAT gene and its use in the identification of novel mutations. Biochem. Biophys. Res. Commun. 281:754–760.
Ofman R. and Wanders R. J. A. (1994). Purification of peroxisomal acyl-CoA:dihydroxyacetonephosphate acyltransferase from human placenta. Biochim. Biophys. Acta Protein Struct. Mol. Enzymol. 1206:27–34.
Paltauf F. (1994). Ether lipids in biomembranes. Chem. Phys. Lipids 74:101–139.
Patel N. C., DelBello M. P., Cecil K. M., Adler C. M., Bryan H. S., Stanford K. E., and Strakowski S. M. (2006). Lithium treatment effects on myo-inositol in adolescents with bipolar depression. Biol. Psychiat. 60:998–1004.
Patishi Y., Lubrich B., Berger M., Kofman O., Van Calker D., and Belmaker R. H. (1996). Differential uptake of myo-inositol in vivo into rat brain areas. Eur. Neuropsychopharmacol. 6:73–75.
Pettegrew J. W., Panchalingam K., Levine J., McClure R. J., Gershon S., and Yao J. K. (2001). Chronic myo-inositol increases rat brain phosphatidylethanolamine plasmalogen. Biol. Psychiat. 49:444–453.
Pike L. J., Han X. L., Chung K. N., and Gross R. W. (2001). Lipid rafts are enriched in plasmalogens and arachidonate-containing phospholipids and the expression of caveolin does not alter the lipid composition of these domains. FASEB J. 15:A20.
Rodemer C., Thai T. P., Brugger B., Kaercher T., Werner H., Nave K. A., Wieland F., Gorgas K., and Just W. W. (2003). Inactivation of ether lipid biosynthesis causes male infertility, defects in eye development and optic nerve hypoplasia in mice. Hum. Mol. Genet. 12:1881–1895.
Rouser G. and Yamamoto A. (1968). Curvilinear regression course of human brain lipid composition changes with age. Lipids 3:284–287.
Schlossman D. M. and Bell R. M. (1977). Microsomal sn-glycerol 3-phosphate and dihydroxyacetone phosphate acyltransferase activities from liver and other tissues. Evidence for a single enzyme catalizing both reactions. Arch. Biochem. Biophys. 182:732–742.
Shaldubina A., Buccafusca R., Johanson R. A., Agam G., Belmaker R. H., Berry G. T., and Bersudsky Y. (2007). Behavioural phenotyping of sodium-myo-inositol cotransporter heterozygous knockout mice with reduced brain inositol. Genes Brain Behav. 6:253–259.
Snyder F., Lee T.-C., and Wykle R. L. (1985). Ether-linked glycerolipids and their bioactive species: Enzymes and metabolic regulation. In: Martonosi A. N. (Ed.), The Enzymes of Biological Membranes. Plenum, New York, pp. 1–58.
Stamps A. C., Elmore M. A., Hill M. E., Kelly K., Makda A. A., and Finnen M. J. (1997). A human cDNA sequence with homology to non-mammalian lysophosphatidic acid acyltransferases. Biochem. J. 326 (Pt 2):455–461
Stoffel W., LeKim D., and Heyn G. (1970). Metabolism of sphingosine bases. XIV. Sphinganine (dihydrosphingosine), an effective donor of the alk-1-enyl chain of plasmalogens. Hoppe Seylers. Z. Physiol. Chem. 351:875–883.
Suzuki T. (2002). Lipid rafts at postsynaptic sites: Distribution, function and linkage to postsynaptic density. Neurosci. Res. 44:1–9.
Thai T. P., Heid H., Rackwitz H. R., Hunziker A., Gorgas K., and Just W. W. (1997). Ether lipid biosynthesis: isolation and molecular characterization of human dihydroxyacetonephosphate acyltransferase. FEBS Lett. 420:205–211.
Toews A. D. and Horrocks L. A. (1976). Developmental and aging changes in protein concentration and 2 , 3,-cyclic nucleosidemonophosphate phosphodiesterase activity (EC 3.1.4.16) in human cerebral white and gray matter and spinal cord. J. Neurochem. 27:545–550.
Visser W. F., van Roermund C. W., Waterham H. R., and Wanders R. J. (2002). Identification of human PMP34 as a peroxisomal ATP transporter. Biochem. Biophys. Res. Commun. 299:494–497.
Wanders R. J. A. and Waterham H. R. (2006). Peroxisomal disorders: The single peroxisomal enzyme deficiencies. Biochim. Biophys. Acta Mol. Cell Res. 1763:1707–1720.
Webber K. O. and Hajra A. K. (1993). Purification of dihydroxyacetone phosphate acyltransferase from guinea pig liver peroxisomes. Arch. Biochem. Biophys. 300:88–97.
Wells M. A. and Dittmer J. C. (1967). A comprehensive study of the postnatal changes in the concentration of the lipids of developing rat brain. Biochemistry 6:3169–3175.
West J., Tompkins C. K., Balantac N., Nudelman E., Meengs B., White T., Bursten S., Coleman J., Kumar A., Singer J. W., and Leung D. W. (1997). Cloning and expression of two human lysophosphatidic acid acyltransferase cDNAs that enhance cytokine-induced signaling responses in cells. DNA Cell Biol. 16:691–701.
Whitehouse P. J. (1997). Genesis of Alzheimer’s disease. Neurology 48:2–7.
Williams S. D., Hsu F. F., and Ford D. A. (2000). Electrospray ionization mass spectrometry analyses of nuclear membrane phospholipid loss after reperfusion of ischemic myocardium. J. Lipid Res. 41:1585–1595.
Zheng H., Duclos R. I. J., Smith C. C., Farber H. W., and Zoeller R. A. (2006). Synthesis and biological properties of the fluorescent ether lipid precursor 1-O-[9′–(1″–pyrenyl)]nonyl-sn-glycerol. J. Lipid Res. 47:633–642.
Zomer A. W. M., De Weerd W. F. C., Langeveld J., and van den Bosch H. (1993). Ether lipid synthesis: Purification and identification of alkyl dihydroxyacetone phosphate synthase from guinea-pig liver. Biochim. Biophys. Acta Lipids Lipid Metab. 1170:189–196.
Rights and permissions
Copyright information
© 2008 Springer Science+Business Media, LLC
About this chapter
Cite this chapter
(2008). Biosynthesis of Plasmalogens in Brain. In: Metabolism and Functions of Bioactive Ether Lipids in the Brain. Springer, New York, NY. https://doi.org/10.1007/978-0-387-77401-5_2
Download citation
DOI: https://doi.org/10.1007/978-0-387-77401-5_2
Publisher Name: Springer, New York, NY
Print ISBN: 978-0-387-77400-8
Online ISBN: 978-0-387-77401-5
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)