Regulation of Pyruvate Kinase in Normal and Pathological Conditions

Pyruvate kinase (ATP: pyruvate 2-O-phosphotransferase, EC 2.7.1.40.) catalyzes the conversion of phospho-enol-pyruvate to pyruvate with regeneration of ATP. There are at least three mammalian isoenzymes of pyruvate kinase known, each of which is composed of four identical or nearly identical subunits. ^{1 – 24} According to the nomenclature proposed by Ibsen, these isozymes are designated as L (liver), M (muscle), and K (kidney). ¹ M- and K-isozymes are also frequently designated as M, and M₂, respectively. ^{3 , 13} The subunit constitution of the isozymes can be designated by a subscript, e.g., M₄ for the tetrameric form of the M-isozyme and K₂M₂ to designate a hybrid with two subunits of the K-type protomer and two of the M-type protomer. The presence of hybrid isozymes has been demonstrated in many mammalian tissues, especially from rat organs. ⁶ Data has been reported suggesting the presence of KL hybrids in kidney and intestinal extracts and of KM hybrids in several tissues obtained from various adult mammalian species. ^{7 , 8 , 14 , 18}