AOAH

Acyloxyacyl hydrolase, also known as AOAH, is a is_associated_with::protein which in humans is encoded by the AOAH is_associated_with::gene.

Function
Acyloxyacyl hydrolase (AOAH) is a 2-subunit is_associated_with::lipase which selectively hydrolyzes the secondary (acyloxyacyl-linked) fatty acyl chains from the lipid A region of bacterial is_associated_with::lipopolysaccharides (LPSs, also called endotoxins). This action inactivates LPSs that are sensed by MD-2--Toll-like Receptor 4 (is_associated_with::TLR 4) on animal cells. The enzyme's 2 disulfide-linked subunits are encoded by a single mRNA. The smaller subunit is a member of the saposin-like (SAPLIP) proteins and the larger subunit is a GDSL lipase.

Absence of the enzyme in genetically engineered mice has been associated with distinctive phenotypes. AOAH-deficient animals are unable to inactivate even small amounts of LPS in tissues; it remains bioactive and may pass from cell to cell in vivo for weeks. The LPS-exposed mice develop strikingly high titers of polyclonal antibodies, prolonged hepatomegaly, and innate immune “tolerance” that gives them slow and inadequate responses to bacterial challenge.

AOAH has been highly conserved through evolution; the amino acid sequence of the human enzyme is almost 50% identical to that of the AOAH found in Dictyostelium discoideum, with 100% identity in the GDSL lipase consensus sequences. The enzyme has been found in many invertebrates and all vertebrates studied to date except fish.

A polymorphism in the gene has been associated with chronic rhinosinusitis in 2 different ethnic groups. Other studies have found that AOAH mRNA abundance is linked to HLA-DR alleles that, in turn, have been associated strongly with colitis.