Presenting Author University of Massachusetts Medical School
In a metabolic pathway, a series of metabolites are formed then chemically converted to the next one along the pathway. When this chain of events is broken, such as due to mutation of a pathway enzyme, a massive accumulation of a metabolite can occur and can have deleterious consequences, especially if the metabolite has toxic properties. Here, we describe our recent efforts to identify such toxic metabolites in a systemic manner, and examine their relevance in diseases. When a metabolic pathway is overactive in a cancer cell, blocking enzymes which process a toxic intermediate within that pathway can result in cancer cell selective toxic metabolite accumulation and poisoning, a highly attractive therapeutic strategy. We demonstrate as proofs of principles of this approach, manipulation of the selenocysteine biosynthesis pathway and the de novo sphingolipid biosynthesis pathway, for cancer therapy. We will also discuss how toxic metabolite accumulation can be contributing factors in other such as neurodegenerative disorders, and how metabolic pathway manipulation may be considered as a therapeutic strategy.
Support or Funding Information
This work is supported by the Suh Kyungbae Foundation (SUHF) Young Investigator Award, and NIH T32 CA130807.
