Pyruvate kinase and pyruvate dehydrogenase complex (PK; PDC)

Pyruvate-processing enzymes encompass critical catalysts in cellular energy metabolism, including pyruvate kinase, which finalizes glycolysis by transferring phosphate from phosphoenolpyruvate to ADP to generate pyruvate and ATP, and the pyruvate dehydrogenase complex, a large assembly that decarboxylates pyruvate to acetyl-CoA for TCA cycle entry while producing NADH and CO2. These enzymes regulate the balance between glycolytic flux and oxidative metabolism, with pyruvate kinase existing as tissue-specific isozymes (e.g., PKM2 in tumors favoring aerobic glycolysis, known as the Warburg effect) and PDC tightly controlled by phosphorylation via PDK and energy status. Dysregulation contributes to diseases like cancer, where PKM2 promotes proliferation, and metabolic disorders such as diabetes or congenital PDH deficiency causing lactic acidosis. Drugs targeting these enzymes, like PDC activators, aim to shift metabolism toward oxidation for antitumor effects, but face challenges from ubiquitous roles in energy homeostasis. Overall, they represent high-value but challenging therapeutic nodes due to their central position in intermediary metabolism.

Other names

Pyruvate kinase (pykF, pykA in E. coli; PKL/R/M1/M2 in humans)Pyruvate dehydrogenase complex (PDH, PDC)phosphoenolpyruvate kinasepyruvate decarboxylase complex

Allosteric activation/inhibition (e.g., FBP activates PK); Kinase inhibition (PDK blocks PDC phosphorylation); Competitive substrate inhibition; Tetramer-dimer shift in PKM2