Epigenetic modifications to DNA and histone proteins are known to regulate metabolic gene expression, which in turn impacts metabolite levels. Conversely, the machinery responsible for modifying DNA and histones at the epigenetic level is highly sensitive to metabolites arising from cellular metabolism. Thus, the metabolic changes associated with oncogenesis may affect the epigenetic machinery, creating a feedback loop that synergistically promotes the progression of cancer. This webinar will examine how, by targeting proteins responsible for the crosstalk between epigenetics and metabolism, we may be able to develop new and effective therapeutic options for cancer treatment.
In this Wednesday, June 1, 2016 photo, Amanda Evans-Clark looks over photos of her husband, Joe Clark, and their daughter at their home in Carmel, Ind. He died of advanced colon cancer at 31, after a year of chemotherapy and last-ditch major abdominal surgery. The decision to end treatment had a surprise effect on Clark and his wife. "It was a whole new way of thinking to wrap our minds around," Evans-Clark recalled. No more "fight mode," she said.
Michael L. Mavrovouniotis Department of Chemical Engineering Northwestern University, Evanston, IL 60208-3120, U.S.A. mlmavro @ nwu.edu Abstract We discuss some central issues that arise in the computer representation of the metabolism and its subsystems. We provide a framework for the representation of metabolites and bioreactions at multiple levels of detail. The framework is based on defining an explicit linear mapping of metabolites and reactions from one level of detail to another. A simple reaction mechanism serves as an illustration and shows the emergence of the concept of a catalyst from metabolic abstraction levels. Introduction Many efforts have recently been undertaken to construct models, databases, and computer representations of the metabolism (Reddy et al., 1993, Ochs and Conrow, 1991, Karp and Mavrovouniotis, 1994, Hunter, 1993, and references therein).
Understanding how the tryptophan-kynurenine pathway is regulated in different tissues, and the diverse biological activities of its metabolites, has become of interest to many areas of science. The bioavailability of tryptophan can be affected by factors that range from gut microbiome composition to systemic inflammatory signals. Gut-resident bacteria can directly absorb tryptophan and thus limit its availability to the host organism. The resulting metabolites can have local effects on both microbiome and host cells and even mediate interspecies communication. In addition, the biochemical fate of absorbed tryptophan will be affected by cross-talk with other nutrients and even by individual fitness, because skeletal muscle has recently been shown to contribute to kynurenine metabolism.
Clear cell renal cell carcinoma (ccRCC) is the most common and aggressive form of kidney cancer and undergoes extensive metabolic reprogramming. Courtney et al. infused a glucose isotope into patients with primary ccRCC who were undergoing surgery and traced metabolic and isotopic flux. Compared with cells of the adjacent kidney, tumor cells exhibited prominent glycolysis, whereas the presence of tricarboxylic acid (TCA) cycle metabolites (indicating glucose oxidation) was diminished. In one patient who was infused with an acetate isotope (acetate is a direct substrate of the TCA cycle), low TCA cycle turnover of metabolites was also observed. This phenomenon describes the Warburg effect of metabolism in ccRCC and highlights metabolic differences between different types of cancer.