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Pathway Description
Plasmalogen Synthesis
Rattus norvegicus
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2018-08-10
Last Updated: 2023-10-25
Plasmalogens are a class of phospholipids found in animals. Plasmalogens are thought to influence membrane dynamics and fatty acid levels, while also having roles in intracellular signalling and as antioxidants. Plasmalogens consist of a glycerol backbone with an vinyl-ether-linked alkyl chain at the sn-1 position, an ester-linked long-chain fatty acid at the sn-2 position, and a head group attached to the sn-3 position through a phosphodiester linkage. It is the vinyl-ether-linkage that separates plasmalogens from other phospholipids. Plasmalogen biosynthesis begins in the peroxisomes, where the integral membrane protein dihydroxyacetone phosphate acyltransferase (DHAPAT) catalyzes the esterification of the free hydroxyl group of dihydroxyacetone phosphate (DHAP) with a molecule any of long chain acyl CoA. Next, alkyl-DHAP synthase, a peroxisomal enzyme associated with DHAPAT, replaces the fatty acid on the DHAP with a long chain fatty alcohol. The third step of plasmalogen biosynthesis is catalyzed by the enzyme acyl/alkyl-DHAP reductase, which is found in the membrane of both the peroxisome and endoplasmic reticulum (ER). Acyl/alkyl-DHAP reductase uses NADPH as a cofactor to reduce the ketone of the 1-alkyl-DHAP using a classical hydride transfer mechanism. The remainder of plasmalogen synthesis occurs using enzymes in the ER. Lysophosphatidate acyltransferases (LPA-ATs) transfer the acyl component of a polyunsaturated acyl-CoA to the the 1-alkyl-DHAP, creating a 1-alkyl-2-acylglycerol 3-phosphate. The phosphate is then removed by lipid phosphate phosphohydrolase I (PAP-I), and the head group is attached by a choline/ethanolaminephosphotransferase. The majority of plasmalogens have either ethanolamine or choline as a headgroup, although a small amount of serine and inositol-linked ether-phospholipids can also be found. In the final step, the vinyl-ether linkage is created by plasmanylethanolamine desaturase, which catalyzes the formation of a double bond in the alkyl chain of the plasmalogen.
References
Plasmalogen Synthesis References
Lundby A, Secher A, Lage K, Nordsborg NB, Dmytriyev A, Lundby C, Olsen JV: Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues. Nat Commun. 2012 Jun 6;3:876. doi: 10.1038/ncomms1871.
Pubmed: 22673903
Gunawan J, Rabert U, Volkl A, Debuch H: Kinetic studies of alkyl-dihydroxyacetone-phosphate (alkyl-glycerone-phosphate) synthase in peroxisomes of rat liver. Biol Chem Hoppe Seyler. 1990 Apr;371(4):339-44.
Pubmed: 2340111
Zomer AW, de Weerd WF, Langeveld J, van den Bosch H: Ether lipid synthesis: purification and identification of alkyl dihydroxyacetone phosphate synthase from guinea-pig liver. Biochim Biophys Acta. 1993 Oct 13;1170(2):189-96. doi: 10.1016/0005-2760(93)90070-p.
Pubmed: 8399344
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Pubmed: 15057822
Jasinska R, Zhang QX, Pilquil C, Singh I, Xu J, Dewald J, Dillon DA, Berthiaume LG, Carman GM, Waggoner DW, Brindley DN: Lipid phosphate phosphohydrolase-1 degrades exogenous glycerolipid and sphingolipid phosphate esters. Biochem J. 1999 Jun 15;340 ( Pt 3):677-86.
Pubmed: 10359651
Nanjundan M, Possmayer F: Molecular cloning and expression of pulmonary lipid phosphate phosphohydrolases. Am J Physiol Lung Cell Mol Physiol. 2001 Dec;281(6):L1484-93. doi: 10.1152/ajplung.2001.281.6.L1484.
Pubmed: 11704545
Waggoner DW, Gomez-Munoz A, Dewald J, Brindley DN: Phosphatidate phosphohydrolase catalyzes the hydrolysis of ceramide 1-phosphate, lysophosphatidate, and sphingosine 1-phosphate. J Biol Chem. 1996 Jul 12;271(28):16506-9. doi: 10.1074/jbc.271.28.16506.
Pubmed: 8663293
This pathway was propagated using PathWhiz -
Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.
Propagated from SMP0000479
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