Regulation of pyruvate kinase M gene expression.

t w t r i p s a t p s b f c ransferase, EC 2.7.1.40), a rate-controlling glycolytic nzyme, catalyses the transfer of a phosphoryl group rom phosphoenolpyruvate to ADP, yielding ATP and yruvate. PK exists in the cytosol and is functional as tetramer. Mammalian PK exists as four isoenzymes, hich are referred to as the L-, R-, M1-, and M2-types, espectively (1). The L-, R-, and M1-PK isoenzymes are issue-specific, while L-PK is predominantly expressed n the liver but is also present in the kidney, small ntestine, and in pancreatic b-cells (1, 2). R-PK is only xpressed in erythrocytes. M1-PK is expressed in skeltal muscle, heart, and brain. In contrast, M2-PK is a biquitous isoenzyme and is found in nearly all tissues r cells. The cDNAs of the rat PK isoenzymes have all been loned (3–6). The nucleotide sequences of Rand L-PK re nearly identical, except for the 59-untranslated reion which includes a portion of the coding sequences nd the 39-non-coding sequences (4). Thus, the -terminal 33 amino acids of R-PK and the 2 -terminal amino acids of L-PK differ for these isoenymes, while the other amino acid sequences are comletely identical. The number of amino acid residues educed from their cDNAs are 574 for R-PK and 543 or L-PK, respectively. The Rand L-PK-specific seuences are encoded by the first and the second exons, espectively. The remaining exons are common to the wo isoenzymes. Thus, both isoenzyme mRNAs are ranscribed from different transcription initiation sites f the PKL gene by means of a tissue-specific promoter 4). The nucleotide sequences of M1and M2-PK are lso identical, except for 160 nucleotide sequences ithin the coding sequences (3). The number of amino cid residues deduced from their cDNAs are 531 for oth forms. Forty five amino acid sequences are differ-