Pyruvate Dehydrogenase Kinase 3 (PDK3)
– PDK3 is one of the four isoenzymes of pyruvate dehydrogenase kinase (PDK1–4) that phosphorylate and inactivate the pyruvate dehydrogenase (PDH) complex.
– By inhibiting PDH, PDK3 reduces the conversion of pyruvate into acetyl-CoA, thereby diverting pyruvate from entry into the tricarboxylic acid (TCA) cycle.
– This shift promotes glycolytic metabolism (even under aerobic conditions), a hallmark of the Warburg effect observed in many cancers.
– PDK3 is typically upregulated in response to hypoxia or metabolic stress, conditions commonly encountered in the tumor microenvironment.
– Its expression can be regulated by hypoxia-inducible factor 1-alpha (HIF-1α) and other metabolic regulators, contributing to the adaptive metabolic reprogramming of cancer cells.
– Upregulated Expression: Elevated levels of PDK3 have been observed in several cancer types, including lung, colon, and breast cancers.
– Metabolic Reprogramming: Overexpression of PDK3 supports the preferential use of glycolysis over oxidative phosphorylation, allowing cancer cells to adapt to hypoxic conditions and rapid proliferation.
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