Bovine and Chicken Pyruvate Kinase Isozymes Intraspecies and Interspecies Hybrids

Allosteric Regulation of Pyruvate Kinase M2 Isozyme Involves a Cysteine Residue in the Intersubunit Contact

“…The mammalian PKs, with exception of the M 1 isozyme, exhibit allosteric properties, as activated homotropically by PEP and heterotropically by fructose-1,6-bisphosphate (FBP) (1)(2)(3). The M 1 isozyme remains fully active, probably due to its intrinsic active conformation in the R-state and, as a result, is regulated by neither PEP nor FBP (1,4).…”

Differential Behavior of Missense Mutations in the Intersubunit Contact Domain of the Human Pyruvate Kinase M2 Isozyme

“…The M 1 isozyme is regulated by neither P-enolpyruvate nor Fru-1,6-P 2 because of its intrinsic active conformation in the R-state (5,6). Under unfavorable conditions such as hypoxia and lack of glucose supply, the anaerobic tissues and tumor cells rely heavily on PKM 2 for ATP production (7). Therefore, stringent control of PK activity is of great importance not only for cell metabolism but also for tumorigenic proliferation.…”

“…There are four different isozymes (L, R, M 1 , and M 2 ) in mammalian tissues, which differ in their regulatory properties. These isozymes are allosteric in nature with the exception of the M 1 form, present in skeletal muscle and brain (3)(4)(5)(6)(7). PKM 2 is a ubiquitous prototype enzyme present in all tissues during the embryonic stage and is gradually replaced by other isozymic forms in specific tissues during development.…”

Conversion of Non-allosteric Pyruvate Kinase Isozyme into an Allosteric Enzyme by a Single Amino Acid Substitution

“…In addition, it is also known that expression of these isozymes shifts from M 2 to M 1 during development of some fetal tissues (2). In contrast to the other PK isozymes, M 1 isozyme usually exhibits neither homotropic nor heterotropic allosteric effects (1,5,6). This isozyme, however, displays cooperative behavior under certain experimental conditions such as the presence of Lphenylalanine, an allosteric inhibitor (11-13).…”

“…Four distinct isozymes, L, R, M 1 , and M 2 , occur in mammalian tissues and differ in regulatory properties. All these isozymes are known to be tetramers and are allosteric enzymes with the exception of M 1 (1,(5)(6)(7)(8).…”