The acyl- and alkyl-glycerone phosphate reductase DHRS7 is involved in the production of distinct plasmalogen species from DHRS7B.

Plasmalogens are ether lipids that constitute mammalian membranes. In their biosynthetic pathway, DHRS7B functions as an alkylglycerone phosphate reductase. Here, we have investigated whether DHRS7, which shares high sequence similarity with DHRS7B, also contributes to plasmalogen production. We generated DHRS7 and DHRS7B knockout (KO) cells, as well as double-KO cells, and quantified ethanolamine plasmalogens (PE[P]s). DHRS7 and DHRS7B were involved in the production of distinct fatty acid species: in the de novo synthesis pathway, DHRS7 contributed most strongly to the synthesis of C18:1 species, followed by C16:0 and C22:4 species, whereas DHRS7B contributed to the synthesis of all species examined. These differences in contribution in the de novo pathway resulted in further differences in the steady-state composition of PE[P]s. DHRS7 and DHRS7B also showed different intracellular localization: endoplasmic reticulum for DHRS7 and peroxisomes for DHRS7B. In vitro, DHRS7 exhibited both alkyl- and acyl-glycerone phosphate reductase activities, similar to DHRS7B. Collectively, our findings indicate that DHRS7 is a previously unreported acyl- and alkyl-glycerone (acyl/alkyl-glycerone) phosphate reductase that differs from DHRS7B in both subcellular localization and the profile of plasmalogen species produced.