Fig. 1. Structural differences in the four pyruvate kinase (PK) isoforms and splicing variants of pyruvate kinases. The PKR (inclusive of exon 2) isoform chiefly exists in red blood cells. The PKL isoform (inclusive of exon 1) is expressed primarily in the liver, intestine, and kidneys. In alternative splicing of the PKM gene, heterogeneous nuclear ribonucleoproteins (hnRNPs) l, A1, and A2 play an essential role. In the conversion of PKM1 and PKM2, transcription factor serine/arginine-rich splicing factor-3 (SRSF-3) also plays a key role. The PKM1 (exclusively exon 9) isoform is exclusively found in highly catabolic tissues like the heart, brain, and muscles. PKM2 (exclusively exon 10) is generally present in all proliferative and cancer cells. PTB is polypyrimidine tract binding protein.