Platelet-activating factor acetyltransferase (LPCAT2) (LPCAT2)

Platelet-activating factor acetyltransferase, specifically the Lysophosphatidylcholine acyltransferase 2 (LPCAT2) isoform, is a critical enzyme in the biosynthesis of Platelet-Activating Factor (PAF), a potent phospholipid mediator of inflammation and anaphylaxis [UniProt, 2024]. It catalyzes the transfer of an acetyl group from acetyl-CoA to 1-alkyl-lyso-sn-glycero-3-phosphocholine (lyso-PAF) via the remodeling pathway, a process that is significantly upregulated during inflammatory responses [Shindou et al., 2007]. Unlike the constitutively active LPCAT1, LPCAT2 is highly inducible in inflammatory cells such as macrophages and neutrophils following stimulation by Toll-like receptor 4 (TLR4) or other pro-inflammatory cytokines [Harayama et al., 2014]. This enzyme plays a pivotal role in the pathogenesis of asthma, allergic reactions, and chronic inflammatory pain by driving the rapid production of PAF [Yamamoto et al., 2011]. Pharmacological inhibition of LPCAT2, currently explored through experimental compounds like TSI-01, aims to selectively reduce PAF levels to treat inflammatory conditions without disrupting the basal lipid metabolism handled by other acyltransferases [Shindou et al., 2013]. Consequently, it is considered a promising therapeutic target for managing acute and chronic inflammation where PAF overproduction is a key driver [Tsoupras et al., 2018].

Other names

1-alkyl-2-lyso-sn-glycero-3-phosphocholine acetyltransferaseLyso-PAF acetyltransferaseLysophosphatidylcholine acyltransferase 2Acetyl-CoA:lyso-PAF acetyltransferaseLPCAT2

Inhibition of the enzymatic conversion of lyso-PAF to PAF, thereby reducing the levels of the pro-inflammatory mediator PAF.