Oxaloacetate: signaling molecule, molecular mechanisms of interaction, prospects for clinical application

Abstract

Small molecules make up a majority of cellular molecules, their intracellular concentrations vary over a wide range, and they are involved in a multifarious molecular transformations. However, there is not enough information about how small molecules regulate protein functions through intermolecular binding, which creates an urgent need for fundamental research and the study of the metabolites’ role. Our attention was focused on small molecules located at the intersection point of metabolic pathways of proteins, fats, carbohydrates, the structural and functional potential of which provides numerous biomolecular processes. The intermediates availability can regulate energy and intermediate metabolism, cellular redox potential, and production of adenosine triphosphate, determining the direction of metabolism that is priority for the cell at this point in time. Of particular interest in the study of metabolite-protein interactions are those studies that can reveal new enzyme-substrate relationships and cases of metabolite-induced remodeling of protein complexes. The review is devoted to the study of the role of the small molecule oxaloacetate and malate, as well as malate dehydrogenase involved in their transformations, the activity of which can be used as a diagnostic marker in oncological and neurodegenerative diseases. Oxaloacetate has protective and promitochondrial effects, it serves as a neuroprotector, prevents inflammation and neurodegeneration. The penetration of oxaloacetate through the blood-brain barrier into the central nervous system was established, which became a prerequisite for conducting preclinical trials of drugs containing it in models of Alzheimer's disease and ischemic stroke.

Keywords

protein-metabolite interactions / oxaloacetate / neuroprotective effects / malate dehydrogenase / small molecules / energy metabolism / review

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