Pyruvate Kinase

Kinetic studies of the pyruvate kinases of rat and human tissues have led to the identification of three classes of isoenzymes with qualitative differences in regulatory properties. Class L, the major component in liver extracts and a minor component of kidney extracts, shows markedly sigmoidal kinetics with respect to the concentration of phosphoenolpyruvate, allosteric inhibition by ATP and alanine, and activation by fructose 1,6‐bisphosphate. Class A, present in adipose tissue, and the major component in kidney and the minor one in liver, shows slightly sigmoidal substrate saturation curves and is allosterically inhibited by alanine and activated by fructose 1,6‐bisphosphate. Class M, present in muscle and brain, has none of the above regulatory properties. The activities of the pyruvate kinases of classes L and A respond immediately to changes in the concentration of the effectors alanine and fructose 1,6‐bisphosphate. The two regulatory isoenzymes are strongly inhibited by three amino acids: alanine, cysteine, and phenylalanine. Cysteine is the stronger inhibitor for class L, while phenylalanine is the stronger one for class A. The allosteric inhibition is stereospecific for the l‐amino acids in contrast with the weak isosteric inhibition of muscle pyruvate kinase by l‐ or d‐alanine as analogue of the product. The allosteric inhibition of pyruvate kinase L by ATP is highly specific in contrast with a rather wide specificity of this enzyme for nucleoside diphosphates as acceptor substrates.