PDHK3 or Pyruvate Dehydrogenase Kinase 3 is a member of the PDHK family that phosphorylate and inactivate the Pyruvate Dehydrogenase (PDH). PDH is a mitochondrial multienzyme complex that catalyzes the oxidative decarboxylation of pyruvate and is one of the major enzymes responsible for the regulation of homeostasis of carbohydrate fuels in mammals. HIF-1 induces PDHK3 expression leading to inhibition of mitochondrial respiration. Forced expression of PDHK3 in cancer cells results in increased lactic acid accumulation and drugs resistance, whereas knocking down PDHK3 inhibits hypoxia-induced cytoplasmic glycolysis and cell survival.
The Journal of biological chemistry, 283(42), 28106-28114 (2008-08-23)
The switch of cellular metabolism from mitochondrial respiration to glycolysis is the hallmark of cancer cells and associated with tumor malignancy. However, the mechanism of this metabolic switch remains largely unknown. Herein, we reported that hypoxia-inducible factor-1 (HIF-1) induced pyruvate
The Journal of biological chemistry, 270(48), 28989-28994 (1995-12-01)
Recent evidence from this laboratory indicates that at least two isoenzymic forms of pyruvate dehydrogenase kinase (PDK1 and PDK2) may be involved in the regulation of enzymatic activity of mammalian pyruvate dehydrogenase complex by phosphorylation (Popov, K.M., Kedishvili, N.Y., Zhao
Warburg effect enhances glucose to lactate conversion in tumor cells, regardless of oxygen levels; impacting cancer metabolism since 1924.
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