alkylDHAP

alkylDHAP is the abbreviated form of alkyl‑dihydroxyacetone phosphate, an essential intermediate in the biosynthesis of ether‑phospholipids, including plasmalogens and alkyl‑acyl‑glycerophospholipids. The molecule consists of the glycerol backbone of dihydroxyacetone phosphate in which the 1‑position aldehyde group is replaced by an alkyl chain linked via an ether bond. The addition of the alkyl group converts the diol phosphate into a tetrahedral alkyl‑DHA, which can thereafter be converted into the phospholipid headgroup.

The formation of alkylDHAP is catalysed by the enzyme alkyl‑dihydroxyacetone phosphate synthase (ADAPS) in the peroxisomal membrane. ADAPS uses a substrate of dihydroxyacetone phosphate and a fatty alkyl‑CoA to exchange the acyl group of a diacylglycerol‑3‑phosphate substrate with the alkyl chain, releasing malonyl‑CoA as a by‑product. In mammalian cells this pathway is the first committed step of plasmalogen synthesis, which ultimately yields vinyl‑ether bonds characteristic of plasmalogens.

After formation, alkylDHAP undergoes phosphorylation and reduction steps mediated by alkyl‑DHA‑phosphate reductase and related phosphatases, producing alkyl‑glycerone phosphate that is incorporated into the phosphatidylethanolamine or phosphatidylserine backbones. The resulting ether lipids are crucial for membrane fluidity, antioxidant activity, and signal transduction.

Defects in the enzymes that generate or metabolise alkylDHAP are linked to peroxisomal disorders such as rhizomelic chondrodysplasia punctata and rhizomelic acrotelism, which are characterised by reduced plasmalogen levels and skeletal abnormalities. Consequently, alkylDHAP represents a key metabolic crossroads and a target for therapeutic intervention in disorders of peroxisomal lipid metabolism.