LPIAT1/MBOAT7 contains a catalytic dyad transferring polyunsaturated fatty acids to lysophosphatidylinositol

Human membrane bound O-acyltransferase domain-containing 7 (MBOAT7), also known as lysophosphatidylinositol acyltransferase 1 (LPIAT1), is an enzyme involved in the acyl-chain remodeling of phospholipids via Lands' cycle. The MBOAT7 rs641738 variant has been associated with entire spectrum fatty liver disease (FLD) and neurodevelopmental disorders, but exact enzymatic activity catalytic site protein are still unestablished. wild type three mutants missing putative residues (N321A, H356A, N321A + H356A) were produced into Pichia pastoris, purified using Ni-affinity chromatography. was assessed measuring incorporation radiolabeled acids lipid acceptors. preferentially transferred 20:4 20:5 polyunsaturated (PUFAs) to (LPI). On contrary, showed weak for transferring saturated unsaturated acids, regardless substrate. Missense mutations result a loss activity. Thus, catalyzes transfer PUFAs shows highest affinity LPI, missense at dyad inhibit protein. Our findings support hypothesis that association between increased risk NAFLD mediated by changes hepatic phosphatidylinositol remodeling. Taken together, knowledge gives insights understanding on basis FLD.