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Sia Mahajan

How acidic cells can lead to cancer

Our body needs a certain pH level—the amount of H+ ions in any media— to maintain ideal organ, cell, and bodily functions. The body has very sensitive enzymes that are most efficient between a blood pH level of 7.3-7.35. When the body is too acidic or alkaline, it allows for many diseases, fungi, harmful bacteria to thrive, but the helpful ones die. While the pH of blood and saliva are important, two other types of pH are commonly overlooked: extra and intracellular pH

the pH scale measures the amount of free hydrogen ions in a substance


The survival of cells are mainly dependent on the acid-base balance (pH). Looking at the intracellular pH can indicate potential negative changes in a macro-spective lense, and measuring the pH of individual organelles provides information on overall cell function. Intercellular and extracellular pH balance is vital for metabolic function, cell growth, and even contractions in muscle cells. We know that these two pH levels are the crux of overall health, and a recent study conducted by Pawel Swietach and his team have found a link between cellular pH and cancer development.


Cellular respiration occurs inside the cell and the products, CO2 and lactic acid, are produced (intracellular pH is more acid), and to maintain the pH balance, the extracellular pH is more alkaline. The cell membrane separates the two, but allows for select H+ and HCO3- ions to pass through, which in turn effectively change the pH. The membrane has an active transport where H+/H+-equivalents help to maintain the pHi to be acidic and the pHe alkaline. By controlling this transport and using a catalyst enzyme (carbonic acid/CA), tumor cells can create the ideal pH balance to thrive — the opposite conditions for health cells to survive.


image of a hydrogen ion pump regulating the concentration of H+ ions, which helps to maintain the overall cell pH and helps to expel waste generated from cellular respiration


With tissue imaging and dyes, scientists were able to control the pH levels in tumor cells and determined some of the hallmarks of cancer growth. Unlike normal tissue, they saw that tumor cells had a pHe highly acidic and the pHi was alkaline. Tumors expel CO2 and H+-lactate through diffusion to make the pHi alkaline. The the catalyst, CA, helps to speed this up and explains why tumor cells grow faster than regular cells. In healthy cells, the H+/H+-equivalents and the release of H+ ions through ATP breakdown contribute to maintain pH homeostasis; however, tumor cells control the H+/H+-equivalents and no matter how much acid is produced the pHi remains alkaline, which ultimately lets the tumor spread. Looking at the intra and extracellular pH, scientists can determine if you are at risk of developing tumors or if tumors are present, they can tell how advanced it is.


Cells have the ability to control their internal and external pH levels through their membrane and pH regulating proteins. Cell mutations that lead to tumor formation obstructs this process, so the cancer mass controls what pH level is present. Exploiting the acidity and alkalinity lets the cancer cell overpower the host cell and allows for the mutated cell to spread. Advancements in physiological, biochemical, and genetic approaches have been made by trying to use the biological effect that pH has to tackle cancer growth and production.







Syntax:

pHi = intracellular pH

pHe = extracellular pH



References

Swietach, Pawel, et al. “The Chemistry, Physiology and Pathology of PH in Cancer.” Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, The Royal Society, 3 Feb. 2014, www.ncbi.nlm.nih.gov/pmc/articles/PMC3917353/.



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