Functional Roles of Metabolic Intermediates in Regulating the Human Mitochondrial NAD(P)⁺-Dependent Malic Enzyme.

ABSTRACT: Human mitochondrial NAD(P)⁺-dependent malic enzyme (m-NAD(P)-ME) has a dimer of dimers quaternary structure with two independent allosteric sites in each monomer. Here, we reveal the different effects of nucleotide ligands on the quaternary structure regulation and functional role of the human m-NAD(P)-ME exosite. In this study, size distribution analysis was utilized to investigate the monomer-dimer-tetramer equilibrium of m-NAD(P)-ME in the presence of different ligands, and the monomer-dimer (K_d,12) and dimer-tetramer (K_d,24) dissociation constants were determined with these ligands. With NAD⁺, the enzyme formed more tetramers, and its K_d,24 (0.06 µM) was 6-fold lower than the apoenzyme K_d,24 (0.34 µM). When ATP was prese

SUBMITTER: Hsieh JY 

PROVIDER: S-EPMC6591397 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature