The Effect of Alpha Lipoic Acid (ALA) on <i>S. cerevisiae </i>Cell Proliferation

Abstract

This experiment investigates what effect ALA may have on the growth of S. cerevisiae, based on extensive studies that have been conducted previously on the therapeutic capabilities of ALA (α-lipoic acid) in various cancers because of its potent antioxidant and apoptotic effects. It manages this because it serves a significant role in enzymatic processes crucial to energy production in cells. In energy metabolism, ALA is responsible for generating acetyl-CoA from pyruvate, and it thus plays a large role in the PDC (pyruvate dehydrogenase complex), an important link connecting glucose metabolism with the citric acid cycle [1]. It helps to shuttle carbon into aerobic respiration, specifically for converting pyruvate into acetyl-CoA and the formation of NADH and carbon dioxide. The process is regulated by enzymes called PDKs, which serve to catalyze suppression of the PDC when the cellular environment becomes nutrient-limited, or glucose scarce. PDKs are speculated to be able to inactivate the PDC via phosphorylation, thus preserving pyruvate for a different metabolic pathway. It is known that overexpression of PDKs blocks oxidative decarboxylation of pyruvate, so targeting the inhibition of PDKs could upregulate PDC activity [2]. Studies have revealed that PDC inhibition is associated with the mechanisms of many metabolic disorders, even cancer (Stacpoole, 2017). In S.cerevisiae cells, which are model organisms for cancer studies, energy is generated typically anaerobically through alcohol fermentation, until this is impacted and it switches to metabolism controlled by the citric acid cycle. This slows down cell proliferation, so it is predicted that as ALA concentrations are increased, cell proliferation will decrease, as indicated by an average cell count of each culture. After experimentation, results revealed that each ALA concentration, 0.125% (2.37×10-20), 0.25% (1.49×10-16), 0.5% (6.41×10-16), and 1% (9.36×10-18), significantly reduced the cell count of their respective cell culture, as compared to the control of 0% ALA. Also, alcohol test strips revealed that with higher concentrations, the cells switched to aerobic respiration as no alcohol was being produced, so fermentation was stopped. This supports the hypothesis that increasing concentrations of ALA will lead to a decrease in cell proliferation, and may indicate that ALA upregulates PDC activity via inhibition of PDKs, which makes it a potential candidate in adjuvant therapies for cancer treatment.