Figure 3

Initial steps of plasmalogen biosynthesis. Plasmalogen biosynthesis requires enzymes located in peroxisomes and the endoplasmic reticulum. The initial step, catalyzed by the peroxisomal enzyme dihydroxyacetonephosphate acyltransferase (GNPAT), is the acylation of dihydroxyacetone phosphate (DHAP) at the sn-1 position to form 1-acyl-DHAP [34]. Fatty acyl-CoA reductase (FAR1 and/or FAR2), located on the cytoplasmic aspect of the peroxisomal membrane, catalyzes the NADPH-dependent conversion of a fatty acyl-CoA to the corresponding fatty alcohol [33]. The fatty alcohol enters the peroxisome and displaces the sn-1 fatty acid in a reaction catalyzed by alkyl-dihydroxyacetone phosphate synthase (AGPS), resulting in formation of 1-akyl-DHAP, which has an ether linkage [35]. Subsequent enzymatic steps occur outside the peroxisome, including the reduction of alkyl-dihydroxyacetone phosphate to alkyl-glycerophosphate, addition of an acyl group in the sn-2 position, desaturation of the alkyl group to an alkenyl group, and addition of choline or ethanolamine head groups [31]. PEX7 is required for the import of AGPS into peroxisomes and PEX7 mutations, which are the primary cause of RCDP, lead to impaired plasmalogen biosynthesis.