Acyloxyacyl hydrolase (AOAH)

Acyloxyacyl hydrolase (AOAH) is a eukaryotic enzyme produced by myeloid lineage cells such as macrophages, dendritic cells, NK cells, neutrophils, and select renal epithelial cells[1]. AOAH consists of two disulfide-linked subunits derived from a single mRNA: a saposin-like small subunit thought to facilitate lipid binding, and a large catalytic GDSL-lipase subunit with a serine-based active site[1][2][3]. AOAH is uniquely responsible for detoxifying lipopolysaccharide (LPS, endotoxin) from the outer membrane of Gram-negative bacteria by cleaving secondary fatty acyl chains from the lipid A moiety, converting immunostimulatory hexaacyl LPS to a non-stimulatory tetraacyl form[1][2][3][4]. This enzymatic action is crucial for shutting down excessive Toll-like receptor 4 (TLR4)-mediated inflammation and for recovery from LPS-induced immune tolerance after infection. In addition to its central role in defense against Gram-negative bacteria, AOAH activity affects the risk and progression of inflammatory diseases such as asthma and chronic rhinosinusitis, as evidenced by genetic studies associating AOAH polymorphisms with these conditions. Current research suggests that targeted modulation of AOAH activity may have therapeutic potential in infections and inflammatory disorders, but no approved drugs directly targeting AOAH are available[2][4].

Other names

Acyloxyacyl hydrolase small subunitAcyloxyacyl hydrolase large subunitAOAHacyloxyacyl hydrolase (neutrophil)

Enzymatic hydrolysis of the secondary (acyloxyacyl-linked) fatty acyl chains from lipid A of LPS, neutralizing its immunostimulatory effects[1][2][3][4]