Pyruvate Kinase and Warburg Metabolism in Pulmonary Arterial Hypertension
In an elegant editorial appeared in the latest issue of Circulation, Dr. Stephen Archer () comments on our back to back articles appeared in the same issue. "In paired Circulation articles," Archer comments "Caruso et al and Zhang et al fill the Warburg stage with a new cast of Warburg players in pulmonary artery endothelial cells and fibroblasts, respectively. They show that pyruvate production is inhibited by a change in the activity of pyruvate kinase. Pyruvate kinase, the final and rate-limiting step in glycolysis, catalyzes phosphate transfer from phosphoenolpyruvate to ADP, producing pyruvate and ATP (Figure). The mitochondrial supply of pyruvate is further compromised by downregulation of the MPT. Both groups demonstrate that this proglycolytic mechanism is stimulated by upregulation of a heterogeneous nuclear ribonucleoprotein, PTBP1 (polypyrimidine tract-binding protein). PTBP1 acts as a repressor and binds to the flanking sequences of exon 9, thus inhibiting the pyruvate kinase M1 (PKM1) isoform. The resulting increase in the PKM2/PKM1 ratio favors uncoupled glycolysis." Read more at the journal website.