DHAPAcyltransferase

DHAP acyltransferase, also referred to as glyceronephosphate O-acyltransferase (GNPAT) or dihydroxyacetone phosphate acyltransferase (DHAPAT), is a peroxisomal enzyme that catalyzes the acylation of dihydroxyacetone phosphate (DHAP) with a fatty acyl-CoA to form acyl-DHAP. This reaction marks the first committed step in the ether lipid biosynthesis pathway, contributing to the production of plasmalogens, a class of ether phospholipids prominent in many tissues.

Acyl-DHAP is subsequently transformed by alkyl-DHAP synthase to form alkyl-DHAP, in which the acyl chain is replaced with an alkyl group. Through reductions, acylation, and head-group modifications, plasmalogens are produced, providing structural components of membranes and participating in oxidative stress responses and signaling.

In humans, GNPAT encodes DHAP acyltransferase, and the enzyme localizes to peroxisomes. It is closely associated with the ether lipid biosynthesis pathway and interacts with downstream peroxisomal enzymes such as AGPS (alkylglycerone phosphate synthase).

Defects in DHAP acyltransferase or related ether lipid pathway enzymes reduce plasmalogen levels and contribute to peroxisomal disorders, most notably rhizomelic chondrodysplasia punctata (RCDP). Mutations in GNPAT cause RCDP type 1, while mutations in AGPS cause RCDP type 2; both are characterized by skeletal abnormalities, neurologic impairment, and reduced plasmalogen levels.