Effects of Long-Term Cultivation on Medium with Alpha-Ketoglutarate Supplementation on Metabolic Processes of Saccharomyces cerevisiae

Received Jul 6, 2017; Revised Sep 9, 2017; Accepted Sep 17, 2017

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1. Introduction

Alpha-ketoglutarate (AKG), an anion of alpha-ketoglutaric acid, is an important intermediate in the Krebs cycle, which couples amino acid metabolism with glucose oxidation. Studies on animal models have shown that dietary AKG supplementation confers many favorable effects on metabolism, stress resistance, and functional decline of various age-related processes [1–3]. The beneficial effects of AKG are mainly explained by its role as a precursor of certain amino acids such as glutamate, glutamine, leucine, and proline [1, 4]. In addition, AKG can inhibit protein catabolism and activate anabolic processes in animal tissues [5]. Furthermore, exogenous AKG can be involved in the Krebs cycle and thereby intensify mitochondrial respiration [6]. As a result, an increased generation of reactive oxygen species (ROS), by-products of respiratory metabolism, may occur and that leads to oxidative stress development [7]. Thus, the higher ROS levels were shown in nematode Caenorhabditis elegans grown on AKG-supplemented medium [8].

Previous studies suggest that exogenous AKG can induce oxidative stress of low intensity which is accompanied by an activation of defense systems. The mentioned stimulation of protective mechanisms was supposed to be responsible for higher tolerance of AKG-treated organisms to challenge strong oxidative or other kinds of stresses. It may also contribute to preventing functional decline with age [2, 3, 9]. In particular, the AKG-supplemented food prevents an age-related increase in free radical damage to biomolecules in aged mice [3] and increases stress resistance in Drosophila melanogaster flies [9]. Meanwhile, AKG affected differently oxidative stress parameters and levels of storage macromolecules in young and old D. melanogaster [2, 9]. We reported recently that growth on AKG-supplemented medium increased resistance of exponentially growing yeast Saccharomyces cerevisiae to oxidative stress induced by hydrogen peroxide. Moreover, AKG-grown yeast cells showed higher activities of catalase and glutathione reductase and higher levels of thiol-containing compounds, indicating an activation of...