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- W3044004089 abstract "It is well recognized that many metabolic enzymes play essential roles in cancer cells in producing building blocks such as nucleotides, which are required in greater amounts due to their increased proliferation. On the other hand, the significance of enzymes in preventing the accumulation of their substrates is less recognized. Here, we outline the evidence and underlying mechanisms for how many metabolites normally produced in cells are highly toxic, such as metabolites containing reactive groups (e.g., methylglyoxal, 4-hydroxynonenal, and glutaconyl-CoA), or metabolites that act as competitive analogs against other metabolites (e.g., deoxyuridine triphosphate and l-2-hydroxyglutarate). Thus, if a metabolic pathway contains a toxic intermediate, then we may be able to induce accumulation and poison a cancer cell by targeting the downstream enzyme. Furthermore, this poisoning may be cancer cell selective if this pathway is overactive in a cancer cell relative to a nontransformed cell. We describe this concept as illustrated in selenocysteine metabolism and other pathways and discuss future directions in exploiting toxic metabolites to kill cancer cells." @default.
- W3044004089 created "2020-07-29" @default.
- W3044004089 creator A5042130024 @default.
- W3044004089 creator A5071300875 @default.
- W3044004089 creator A5074864332 @default.
- W3044004089 creator A5081791154 @default.
- W3044004089 date "2020-07-24" @default.
- W3044004089 modified "2023-10-02" @default.
- W3044004089 title "Endogenous toxic metabolites and implications in cancer therapy" @default.
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