Author
Christopher T. Lee
Bio: Christopher T. Lee is an academic researcher from University of Alberta. The author has contributed to research in topics: Glycolysis & Apoptosis. The author has an hindex of 2, co-authored 2 publications receiving 1383 citations.
Topics: Glycolysis, Apoptosis, GLUT4, Glucose uptake, Mitochondrion
Papers
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TL;DR: The unique metabolic profile of cancer (aerobic glycolysis) might confer apoptosis resistance and be therapeutically targeted and the orally available DCA is a promising selective anticancer agent.
1,452 citations
TL;DR: It is demonstrated that while insulin has no detectable effect on glucose uptake, phenformin-induced AMPK activation increases glucose uptake 2.5-fold, and suggest that AMPK is a major regulator of glucose uptake in cardiac myocytes.
Abstract: Glucose uptake and glycolysis are increased in the heart during ischemia, and this metabolic alteration constitutes an important contributing factor towards ischemic injury. Therefore, it is import...
18 citations
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TL;DR: Control of p53's transcriptional activity is crucial for determining which p53 response is activated, a decision that must be understood if the next generation of drugs that selectively activate or inhibit p53 are to be exploited efficiently.
2,775 citations
TL;DR: The Warburg effect of aerobic glycolysis is re-examine and a framework for understanding its contribution to the altered metabolism of cancer cells is established.
2,081 citations
TL;DR: The peculiarities of tumor cell metabolism are reviewed to discuss the alterations in signal transduction pathways and/or enzymatic machineries that account for metabolic reprogramming of transformed cells.
2,007 citations
TL;DR: Evidence is presented for a large class of non-oncogenes that are essential for cancer cell survival and present attractive drug targets and theoretical considerations for combining orthogonal cancer therapies are provided.
1,619 citations
TL;DR: It is shown that human cells use reductive metabolism of α-ketoglutarate to synthesize AcCoA for lipid synthesis and support lipid synthesis in mammalian cells.
Abstract: Acetyl coenzyme A (AcCoA) is the central biosynthetic precursor for fatty-acid synthesis and protein acetylation. In the conventional view of mammalian cell metabolism, AcCoA is primarily generated from glucose-derived pyruvate through the citrate shuttle and ATP citrate lyase in the cytosol. However, proliferating cells that exhibit aerobic glycolysis and those exposed to hypoxia convert glucose to lactate at near-stoichiometric levels, directing glucose carbon away from the tricarboxylic acid cycle and fatty-acid synthesis. Although glutamine is consumed at levels exceeding that required for nitrogen biosynthesis, the regulation and use of glutamine metabolism in hypoxic cells is not well understood. Here we show that human cells use reductive metabolism of α-ketoglutarate to synthesize AcCoA for lipid synthesis. This isocitrate dehydrogenase-1 (IDH1)-dependent pathway is active in most cell lines under normal culture conditions, but cells grown under hypoxia rely almost exclusively on the reductive carboxylation of glutamine-derived α-ketoglutarate for de novo lipogenesis. Furthermore, renal cell lines deficient in the von Hippel-Lindau tumour suppressor protein preferentially use reductive glutamine metabolism for lipid biosynthesis even at normal oxygen levels. These results identify a critical role for oxygen in regulating carbon use to produce AcCoA and support lipid synthesis in mammalian cells.
1,482 citations