Ethanolamine plasmalogens

In multiple sclerosis, which is a demyelinating disease, there is loss of both phospholipids (particularly ethanolamine plasmalogen) and of sphingolipids from white matter. Thus, the lipid composition of white matter resembles that of gray matter. The cerebrospinal fluid shows raised phospholipid levels. 

Fig. 9.4 Chemical structures of cellular lipids that act as endogenous antioxidants. Choline plasmalogens (a) ethanolamine plasmalogens (b) ganglioside (c) and vitamin E (a-tocopherol) (d)...

Farooqui A. A., Rapoport S. I., and Horrocks L. A. (1997). Membrane phospholipid alterations in Alzheimer disease deficiency of ethanolamine plasmalogens. Neurochem. Res. 22 523-527. 

Latorre E., Collado M. P, Fernandez I., Aragones M. D., and Catalan R. E. (2003). Signaling events mediating activation of brain ethanolamine plasmalogen hydrolysis by ceramide. Eur. 

Maeba R. and Ueta N. (2004). A novel antioxidant action of ethanolamine plasmalogens in lowering the oxidizability of membranes. Biochem. Soc. Trans. 32 141-143. 

Zommara M., Tachibana N., Mitsui K., Nakatani N., Sakono M., Ikeda I., and Imaizumi K. (1995). Inhibitory effect of ethanolamine plasmalogen on iron- and copper-dependent lipid peroxidation. Free Radical Biol. Med. 18 599-602. 

Myelin is modified plasma membrane. Myelin of the PNS resembles that of the CNS with respect to lipid composition. There is an enrichment in such specialized lipids as cerebroside and ethanolamine plasmalogen, and the high content of cholesterol plays an important role in control of membrane fluidity. The protein composition of PNS myelin is, however, distinct from that of CNS myelin. A single protein, P0, accounts for half of all protein of PNS myelin. Of the other proteins present, most are expressed in the CNS as well as the PNS but in quantitatively different amounts. Prominent among these proteins are myelin basic proteins and myelin-associated glycoprotein. 

Biosynthesis of ethanolamine plasmalogen. Enzymes (1) acyltransferase (2) synthase (3) oxidoreductase (4) acyltransferase (5) phosphatase (6) transferase (7) A -alkyl desaturase. 

Ginsberg L, Rafique S, Xuereb JH, Rapoport SI, Gershfeld NL. Disease and anatomic specificity of ethanolamine plasmalogen deficiency in Alzheimer s disease brain. Brain Res 1995 698 223-226. 

Nieto, M. L., Venable, M. E Bauldry, S. A., Greene, D. G., Kennedy, M., Bass, D. A., Wykle, R. L. (1991). Evidence that hydrolysis of ethanolamine plasmalogens triggers synthesis of plateletactivating factor via a transacylation reaction. J. Biol. Chem. 266, 18699-18706. 

It was not until the 1950s that the precise chemical structure of the alk-l -enyl linkage in ethanolamine plasmalogens was proven, primarily through the combined efforts of... 

In model membranes, ether-linked lipids decrease ion permeability and surface potential, and lower the phase temperature of membrane bilayers when compared to their diacyl counterparts. Ethanolamine plasmalogen is enriched, along with cholesterol, in membrane lipid rafts. These domains have a distinct hydrophobic environment with ordered lipid packing, and plasmalogen can serve to stabilize the interaction of specific raft proteins (Chapter 1). 

The r-alkyl desaturase system, a microsomal mixed-function oxidase responsible for the biosynthesis of ethanolamine plasmalogens from alkyl lipids (Fig. 6), was initially characterized in the early 1970s (F. Snyder, 1971 A. Paltauf, 1973). The reverse of this reaction (i.e., conversion of an alk-l -enyl moiety to an alkyl chain via a reductase) has not been observed. The alkyl desaturase is a unique activity since it can specifically and stereospecifically abstract hydrogen atoms from C-1 and C-2 of the 0-alkyl chain of an intact phospholipid molecule to form the cis double bond of the O-alk-l -enyl moiety. Only intact l-alkyl-2-acyl-in-glycero-3-phosphoethanolamine is known to serve as a substrate for the alkyl desaturase. As with other reactions in complex ether phospholipid synthesis, the molecular identity of the responsible enzyme is unknown. 

Like the acyl-CoA desaturases (Chapter 7), the 1 -alkyl desaturase exhibits the typical requirements of a microsomal mixed-function oxidase. Molecular oxygen, a reduced pyridine nucleotide, cytochrome b, cytochrome reductase, and a terminal desaturase protein that is sensitive to cyanide are all required. The precise reaction mechanism responsible for the biosynthesis of ethanolamine plasmalogens is unknown, but it is clear from an investigation with a tritiated fatty alcohol that only the 15 and 25 (erythro)-labeled hydrogens are lost during the formation of the alk-l -enyl moiety of ethanolamine plasmalogens. 

Fig. 6. Biosynthesis of ethanolamine plasmalogens by I -alkyl desaturase. Components of the enzyme complex responsible for this unusual desaturation between carbons 1 and 2 of the 0-alkyl chain are (I) NADH cytochrome h, reductase, (II) cytochrome b, and (III) Al -alkyl desaturase, which is cyanide-sensitive. GPE, jn-glycero-3-phosphoethanolamine.

Fig. 7. Biosynthesis of choline plasmalogens (plasmenylcholines) via modification of the sn-3 polar head group of ethanolamine plasmalogens (plasmenylethanolamines). These reactions are proposed to be catalyzed directly by (1) a base exchange enzyme or (II) At-methyltransferase. A combination of other enzymatic reactions could also result in replacement of the ethanolamine moiety of plasmenylethanolamine to produce plasmenylcholines the enzymes responsible include (IB) phospholipase C, (IV) the reverse reaction of ethanolamine phosphotransferase, (V) phospholipase D, (VI) phosphohydtolase, and (VII) cholinephosphotransferase. AdoMet, 5-adenosyl-L-methionine AdoHcy, 5-adenosyl-L-homocysteine Etn, ethanolamine GPE, sn-glycero-...

Farooqui AA, Rapoport SI, Horrocks LA (1997) Membrane phospholipid alterations in Alzheimer s disease deficiency of ethanolamine plasmalogens. Neurochem Res 22 523-527 Farooqui AA, Horrocks LA (1998) Lipid peroxides in the free radical pathophysiology of brain diseases. Cell Mol Neurobiol 18 599-608... 

The synthesis of ether phosphatidylethanolamines is analogous to that for the formation of the corresponding phosphatidylcholines (Rosenthal, 1975). The iV-methyl-and AW-dimethyl derivatives have been synthesized from their corresponding phosphatidic acids (Aneja et aL, 1970). The formation of AT-acylphosphatidylethanolamines and other analogues is detailed by Slotboom and Bonsen (1970) and that of ethanolamine plasmalogens in Section 7.5.8. 

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