1-acyl-sn-glycerol-3-phosphate acyltransferase (AGPAT) (AGPAT)

1-acyl-sn-glycerol-3-phosphate acyltransferase (AGPAT), also known as lysophosphatidic acid acyltransferase (LPAAT), is an essential enzyme in the Kennedy pathway for glycerolipid synthesis (UniProt: O15120). It catalyzes the conversion of lysophosphatidic acid (LPA) into phosphatidic acid (PA) by transferring an acyl group to the sn-2 position of the glycerol backbone. This reaction is a critical step in the production of both triacylglycerols and major membrane phospholipids like phosphatidylcholine and phosphatidylethanolamine (PubMed: 15135305). Beyond its metabolic role, the product PA acts as a potent lipid second messenger that regulates various cellular processes, including vesicle trafficking and the activation of pro-survival signaling cascades like the mTOR pathway. Mutations in the AGPAT2 isoform are the primary cause of Berardinelli-Seip Congenital Lipodystrophy type 2, which results in a near-total loss of body fat and severe insulin resistance (PubMed: 12456705). In oncology, AGPAT isoforms are frequently upregulated in several cancers, where they contribute to tumor cell proliferation and resistance to apoptosis. Consequently, AGPAT has emerged as a therapeutic target, with small-molecule inhibitors like CT-2584 being investigated for their ability to disrupt lipid signaling and induce tumor cell death (ClinicalTrials.gov). Therapeutic challenges include the potential for systemic metabolic disruption given the enzyme's central role in lipid homeostasis.

Other names

Lysophosphatidic acid acyltransferaseLPAAT1-acylglycerol-3-phosphate O-acyltransferase1-AGP acyltransferase

Inhibition of the conversion of lysophosphatidic acid to phosphatidic acid, reducing the availability of precursors for glycerolipid synthesis and disrupting pro-survival lipid signaling.