HORMONE-DEPENDENT AND HORMONE-INDEPENDENT CONTROL OF METABOLIC AND DEVELOPMENTAL FUNCTIONS OF MALATE DEHYDROGENASE - REVIEW

Abstract Malate dehydrogenases (MDHs) are specific class of ubiquitous and multimeric oxidative decarboxylases with well conserved amino acid sequences in structurally important regions and with similar overall structural topology. They mostly use malate or oxaloacetate as substrates to generate pyruvate and utilize preferentially NADP or NAD as cofactor. Among species and even within an organism they differ in their subcellular localization and specificity for the cofactor. Comparison across microbial, plant and animal kingdoms show that MDHs were able to adopt tissue-, species- or environmental-specific functions while still keeping main structural features. Although basic principles of MDH regulation are similar to other enzymes and include oligomerization, cofactor binding, divalent cation availability, some of MDH enzymes are regulated also at different levels involving control of hysteresis, protein-protein interaction and gene expression. In this review we concentrate on those aspects of MDH function and regulation in animals that are specifically associated with cell differentiation and proliferation, ontogenic development, hormonal control, and partly with diseases. Accenting these aspects of MDHs provides emerging and new views on their regulatory function in complex eukaryotic metazoan organisms that goes beyond their classical role in basic metabolism.