Ethanolamine plasmalogen, biosynthesis

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

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-...

Information concerning the biosynthesis of choline plasmalogen is somewhat limited. Most of the work on the biological formation of plasmalogens has been done on ethanolamine plasmalogen (see below) rather than choline plasmalogen. An exception is the report of Keenan, Brown and Marks (1961), who showed that C -labelled fatty acids are incorporated in both the acyl ester group and the... 

The a,jS-unsaturated fatty ether is an aldehydogenie group because its hydrolysis releases an a -unsaturated primary alcohol that readily tautomerizes to an aldehyde. Choline, ethanolamine, and serine plasmalogens are found in cardiac and skeletal muscle, brain, and liver. The biosynthesis of phosphatidylethanolamine is shown in Figure 19-5. 

P ADP -I- l-alkyl-sn-glycero-3-phosphate <1> (<1> the product l-alkyl-2-lyso-sn-glycero-3-phosphate is the branch point intermediate in the de novo biosynthesis of ether-linked glycerolipids, plasmanylcholine, i.e. ethanolamine, and corresponding plasmalogenic analogs in membranes or platelet-activating factor PAF [2]) [1, 2]... 

Figure 2. Biosynthesis of plasmalogens in mammalian tissues. Enzymes (1) dihydroxyacetone phosphate acyltransferase (2) 1-acyldihydroxyacetone phosphate synthase (3) 1-alkyldihydroxyacetone phosphate oxidoreductase (4) l-alkyl-5n-glycero-3-phosphate acyltransferase (5) 1-afkyl 2-acyl-5w-glycero-3-phosphohydrolase (6) CDP-ethanolamine transferase (7) l-alkyl-2-acyl-5w-glycero-3-phosphoethanolamine desaturase (8) methyltransferases and base-exchange enzymes. CDP-ethanolamine, cytidine diphosphoethanolamine. CMP, cytidine monophosphate. CoA, coenzyme A. DHAP, dihydroxyacetone phosphate. NADH, nicotinamide adenine dinucleotide, reduced form. NAD, nicotinamide adenine dinucleotide, oxidized form. Pi, phosphate.

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