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. 2013 Jan;95(1):59-65.
doi: 10.1016/j.biochi.2012.06.027. Epub 2012 Jul 4.

Orphan Enzymes in Ether Lipid Metabolism

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Orphan Enzymes in Ether Lipid Metabolism

Katrin Watschinger et al. Biochimie. .
Free PMC article


Ether lipids are an emerging class of lipids which have so far not been investigated and understood in every detail. They have important roles as membrane components of e.g. lens, brain and testis, and as mediators such as platelet-activating factor. The metabolic enzymes for biosynthesis and degradation have been investigated to some extent. As most involved enzymes are integral membrane proteins they are tricky to handle in biochemical protocols. The sequence of some ether lipid metabolising enzymes has only recently been reported and other sequences still remain obscure. Defined enzymes without assigned sequence are known as orphan enzymes. One of these enzymes with uncharacterised sequence is plasmanylethanolamine desaturase, a key enzyme for the biosynthesis of one of the most abundant phospholipids in our body, the plasmalogens. This review aims to briefly summarise known functions of ether lipids, give an overview on their metabolism including the most prominent members, platelet-activating factor and the plasmalogens. A special focus is set on the description of orphan enzymes in ether lipid metabolism and on the successful strategies how four previous orphans have recently been assigned a sequence. Only one of these four was characterised by classical protein purification and sequencing, whereas the other three required alternative strategies such as bioinformatic candidate gene selection and recombinant expression or development of an inhibitor and multidimensional metabolic profiling.


Fig. 1
Fig. 1
Ether lipid metabolism including biosynthesis and degradation of PAF and plasmalogens. Reactions catalysed by orphan enzymes (i.e. enzymes with unknown sequence) are shown in black circles with white lettering and enzymes with recent sequence assignments in grey circles with white lettering. R, carbon side chain of R1, mostly 15 or 17 atoms (=acyl); R2, 14 or 16 atoms (=alkyl); R3, at least 15 atoms, single- or poly-unsaturated (=acyl). For a description of the enzymatic reactions (capital letters) and the metabolites (Arabic numerals, underlined, italic) see text. ENZYMES (A) glycerone-phosphate O-acyltransferase (E.C., (A2) phospholipase A2 (E.C., (B) alkylglycerone-phosphate synthase (E.C., (C) acylglycerone-phosphate reductase (E.C., (D) alkylglycerol kinase (E.C., (E) alkylglycerolphosphate 2-O-acyltransferase (E.C. 2.3.1.-), (F) phosphatidate phosphatase (E.C., (G) ethanolamine-phosphotransferase (E.C., (H) diacylglycerol cholinephosphotransferase (E.C., (I) plasmanylethanolamine desaturase (E.C., (J) a not further characterised transferase (E.C. 2.6.-.-), (K) phospholipase C (E.C., (L) 1-alkylglycerophosphocholine O-acyltransferase (E.C., (M) alkenylglycerophosphocholine hydrolase (E.C., (N) alkenylglycerophosphoethanolamine hydrolase (E.C., (O) 1-O-alkyl-2-acetylglycerophosphocholine esterase (E.C., (P) alkylglycerol monooxygenase (E.C., (Q) long-chain-aldehyde dehydrogenase (E.C., (R) 1-alkenylglycerophosphocholine O-acyltransferase (E.C., (S) 1-alkylglycerophosphocholine O-acyltransferase (E.C., (T) 1-alkenylglycerophosphoethanolamine O-acyltransferase (E.C., (U) alkylglycerophosphate 2-O-acetyltransferase (E.C., (V) alkylacetylglycerophosphatase (E.C., (W) diacylglycerol cholinephosphotransferase (E.C., (X) acetylalkylglycerol acetylhydrolase (E.C., (Y) 1-alkyl-2-acetylglycerol O-acyltransferase (E.C., (Z) alkylglycerophosphocholine O-acetyltransferase (E.C. METABOLITES (1) glycerone phosphate (dihydroxyacetone phosphate), (2) 1-acyl-glycerone 3-phosphate, (3) 1-O-alkyl-glycerone 3-phosphate, (4) 1-O-alkyl-sn-glycero-3-phosphate, (5) 1-O-alkyl-sn-glycerol, (6) 1-O-alkyl-2-acyl-sn-glycero-3-phosphate, (7) 1-O-alkyl-2-acyl-sn-glycerol, (8) 1-O-alkyl-2-acyl-sn-glycero-3-phosphoethanolamine (plasmanylethanolamine), (9) 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine (plasmanylcholine), (10) 1-O-alk-1′-enyl-2-acyl-sn-glycero-3-phosphoethanolamine (plasmenylethanolamine), (11) 1-O-alk-1′-enyl-2-acyl-sn-glycero-3-phosphocholine (plasmenylcholine), (12) 1-O-alkenyl-2-acyl-sn-glycerol, (13) 1-O-alk-1′-enyl-sn-glycero-3-phosphocholine (lysoplasmenylcholine), (14) 1-O-alk-1′-enyl-sn-glycero-3-phosphoethanolamine (lysoplasmenylethanolamine), (15) fatty aldehyde, (16) sn-glycero-3-phosphocholine, (17) sn-glycero-3-phosphoethanolamine, (18) 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (PAF), (19) 1-O-alkyl-sn-glycero-3-phosphocholine (lyso-PAF), (20) 1-O-alkyl-sn-glycero-3-phosphoethanolamine, (21) glycerol or sn-glycero-3-phosphocholine or sn-glycero-3-phosphoethanolamine, (22) long-chain fatty acid, (23) 1-O-alkyl-2-acetyl-sn-glycero-3-phosphate, (24) 1-O-alkyl-2-acetyl-sn-glycerol, (25) 1-O-alkyl-sn-glycerol, (26) 1-O-alkyl-2-acetyl-3-acyl-sn-glycerol.

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