Role of creatine kinase isoenzymes on muscular and cardiorespiratory endurance - Genetic and molecular evidence

The ability to perform well in activities that require muscular and cardior espiratory endurance is a trait influenced, in a considerable part, by the genetic makeup of individuals. Early studies of performance and recent scan s of the human genome have pointed at various candidate genes responsible f or the heterogeneity of these phenotypes within the population. Among these are the genes for the various creatine kinase (CK) isoenzyme subunits. CK and phosphocreatine (PCr) form an important metabolic system for temporal a nd spatial energy buffering in cells with large variations in energy demand . The different CK isoenzyme subunits (CK-M and CK-B) are differentially ex pressed in the tissues of the body. Although CK-M is the predominant form i n both skeletal and cardiac muscle, CK-B is expressed to a greater extent i n heart than in skeletal muscle. Studies in humans and mice have shown that the expression of CK-B messenger RNA (mRNA) and the abundance and activity of the CK-MB dimer increase in r esponse to cardiorespiratory endurance training. Increases in muscle tissue CK-B content can be energetically favourable because of its lower Michaeli s constant (K-m) for ADP. The activity of the mitochondrial isoform of CK ( Scmit-CK) has also been significantly and positively correlated to oxidativ e capacity and to CK-MB activity in muscle. In mice where the CK-M gene has been knocked out, significant increases in fatigue resistance together wit h cellular adaptations increasing aerobic capacity have been observed. Thes e observations have led to the notion that this enzyme may be responsible f or fatigue under normal circumstances, most likely because of the local cel l compartment increase in inorganic phosphate concentration. Studies where the Scmit-CK gene was knocked out have helped demonstrate that this isoenzy me is very important for the stimulation of aerobic respiration. Human stud ies of CK-M gene sequence variation have shown a significant association be tween a polymorphism, distinguished by the NcoI restriction enzyme, and an increase in cardiorespiratory endurance as indexed by maximal oxygen uptake following 20 weeks of training. In conclusion, there is now evidence at the tissue, cell and molecular leve l indicating that the CK-PCr system plays an important role in determining the phenotypes of muscular and cardiorespiratory endurance. It is envisione d that newer technologies will help determine how the genetic variability o f these genes (and many others) impact on performance and health-related ph enotypes.