The antidepressant drug sertraline is a novel inhibitor of yeast Pah1 and human lipin 1 phosphatidic acid phosphatases.

ABSTRACT: Phosphatidic acid phosphatase (PAP) is an evolutionarily conserved eukaryotic enzyme that catalyzes the Mg²⁺-dependent dephosphorylation of phosphatidic acid to produce diacylglycerol. The product and substrate of PAP are key intermediates in the synthesis of triacylglycerol and membrane phospholipids. PAP activity is associated with lipid-based cellular defects indicating the enzyme is an important target for regulation. We identified that the antidepressant sertraline is a novel inhibitor of PAP. Using Saccharomyces cerevisiae Pah1 as a model PAP, sertraline inhibited the activity by a noncompetitive mechanism. Sertraline also inhibited the PAP activity of human lipin 1 (α, β, and γ), an orthologue of Pah1. The inhibitor constants of sertraline for the S. cerevisiae and human

SUBMITTER: Stukey GJ 

PROVIDER: S-EPMC11721541 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature