PCL486H1 Lecture Notes - Lecture 10: Protein Kinase Inhibitor, Glut1, Tumor Suppressor Gene
26 Feb 2017
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Pi3k/pdk1 controls pyruvate entry into the tca cycle. Inhibits pyruvate acetyl coa synthesis : thus it goes down the ldh pathway lactate. Competition on between ldh and pyruvate dehydrogenase, taking it to the tca. Pdk1 phosphorylation of pdh inhibits its activity preventing pyruvate from becoming acetyl-coa. This is a crucial determinant of whether glucose is oxidized in the mitochondria or turned into lactate. In this sense pdk1 is the warburg kinase forcing it into the warburg metabolism: controls the pivotal point distinguishing cancer cells from normal ones. Tca cycle: there are a number of arrows in and out. A number of the intermediates of this cycle can exit and become other things: oxaloactetate asparginine. If cancer cells bock the entry of pyruvate into this cycle through pdk1, then this is important: this is an anapleroti centre (convert carbon into other molecules) The tca cycle is not only about generating molecules: metabolic pathways can be used to generate other molecules.
