American Journal of Medical and Biological Research
ISSN (Print): 2328-4080 ISSN (Online): 2328-4099 Website: http://www.sciepub.com/journal/ajmbr Editor-in-chief: Apply for this position
Open Access
Journal Browser
Go
American Journal of Medical and Biological Research. 2018, 6(2), 21-26
DOI: 10.12691/ajmbr-6-2-1
Open AccessArticle

The Effect of Alpha Lipoic Acid (ALA) on S. cerevisiae Cell Proliferation

Henna Purewal1,

1Biotechnology High School, United States

Pub. Date: July 21, 2018

Cite this paper:
Henna Purewal. The Effect of Alpha Lipoic Acid (ALA) on S. cerevisiae Cell Proliferation. American Journal of Medical and Biological Research. 2018; 6(2):21-26. doi: 10.12691/ajmbr-6-2-1

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.

Keywords:
PDKs PDC aerobic respiration citric acid cycle energy metabolism alpha-lipoic acid ALA S. cerevisiae cancer

Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

References:

[1]  Zhang, S., Hulver, M. W., McMillan, R. P., Cline, M. A., & Gilbert, E. R. (2014). The pivotal role of pyruvate dehydrogenase kinases in metabolic flexibility. Nutrition & Metabolism, 11, 10.
 
[2]  Zhang, W., Zhang, S.-L., Hu, X., & Tam, K. Y. (2015). Targeting Tumor Metabolism for Cancer Treatment: Is Pyruvate Dehydrogenase Kinases (PDKs) a Viable Anticancer Target? International Journal of Biological Sciences, 11(12), 1390-1400.
 
[3]  Paul M. Bingham and Zuzana Zachar (2012). The Pyruvate Dehydrogenase Complex in Cancer: Implications for the Transformed State and Cancer Chemotherapy, Dehydrogenases, Prof. Rosa Angela Canuto (Ed.), InTech, Available from: https://www.intechopen.com/books/dehydrogenases/the-pyruvate-dehydrogenase-complex-in-cancer-implications-for-the-transformed-state-and-cancer-chemo.
 
[4]  Feuerecker, B., Pirsig, S., Seidl, C., Aichler, M., Feuchtinger, A., Bruchelt, G., & Senekowitsch-Schmidtke, R. (2012). Lipoic acid inhibits cell proliferation of tumor cells in vitro and in vivo. Cancer Biology & Therapy, 13(14), 1425-1435.
 
[5]  Karathia H, Vilaprinyo E, Sorribas A, Alves R (2011) Saccharomyces cerevisiae as a Model Organism: A Comparative Study. PLoS ONE 6(2): e16015.
 
[6]  James A.Gordon,Cook Ritchard M.,West Shauna M. and Lindsay J.Gordon(1995), The pyruvate dehydrogenase complex of Saccharomyces cerevisiae is regulated by phosphorylation, FEBS Letters, 373.
 
[7]  Massachusetts Institute of Technology. (2002). How To Use A Hemocytometer. Retrieved from https://biology.mit.edu/sites/default/files/hemacytometer%20activity%20revised%207-23-13.pdf.
 
[8]  Korotchkina LG, L. (2004). R-Lipoic Acid Inhibits Mammalian Pyruvate Dehydrogenase Kinase. Taylor and Francis Online. Retrieved 16 January 2018, from http://www.tandfonline.com/doi/abs/10.1080/10715760400004168.