Abstract
Phosphofructokinase (PFK) plays a key role in glycolysis, and deficiency of the muscle isozyme of PFK (PFK-M)is a typical clinical entity presenting as myogenic hyperuricemia The control of glycolysis at the PFK step might hold a key to the purine degradation observed in exercising muscles in patients with myogenic hyperuricemia. Our purpose in this study was to clarify the physiological significance of alternative splicing events (type A/B/C and exon 11 skipping) in the human PFK-M gene. By RT-PCR method, we identified the tissue specific distribution of the alternative transcripts in human tissues. In addition to type C, type A and B mRNA were found to be exclusively expressed in skeletal muscle, in which exon skipping was rarely observed. Other human tissues including the liver, kidney, stomach, pancreas, placenta and reticulocytes, expressed only type C mRNA. Exon skipping was clearly evidented in all tissues expressing type C mRNA other than muscle. The secondary structure and the hydrophobic moment of the gene product with exon skipping were predicted and were compared with those of the non-skipping product. with exon skipping the critical conformational changes would occur with skipping of exon 11.
These results suggest that the alternative splicing events observed in PFK-M gene contribute to the tissue-specific regulation of PFK activity.
