Role of myoglobin in regulating respiration

The 1H NMR Val E11 signal provides a unique opportunity to observe carbon monoxide (CO) inhibition of Mb in the in vivo myocardium and to assess the functional role of Mb in regulating respiration. Upon carbon monoxide infusion, the MbO2 Val E11 signal at -2.76 ppm gradually disappears, and a new signal at -2.26 ppm, corresponding to MbCO, emerges. These signals yield the intracellular partial pressure of both O2 and CO and the extent of Mb inactivation, since CO binds more tightly to Mb than O2. Although contractile function decreases slightly to a steady state level, it shows no dose dependence on pCO. Up to 80% MbCO saturation, the contractile function remains at the steady state level. Neither the PCr concentration nor the oxygen consumption rate is significantly perturbed. Above 80% MbCO saturation, the oxygen consumption rate starts to decline. The experimental observations raise provocative questions about the functional role of Mb in the cell.