MATHEMATICAL-MODELING OF THE ROLE OF INTRACELLULAR AND EXTRACELLULAR ACTIVITY OF CARBONIC-ANHYDRASE AND MEMBRANE PERMEABILITIES OF HCO3-, H2O AND CO2 IN O-18 EXCHANGE

Numerical simulation of O-18 exchange between CO2, H2O and HCO3- expla ins the ratio mass 46/mass 44 (=(COO)-O-18-O-16/(CO2)-O-16) measured b y mass spectrometry to approximately 1% relative mean difference. in t he presence of intact red blood cells the reaction takes place extra-a nd intracellularly at different reaction rates. Because CO2 hydration/ dehydration is accelerated intracellularly by carbonic anhydrase, a di fference in intra- and extracellular concentration of labelled reactan ts occurs. The ensuing transfer of reactants across the cell membrane depends on their membrane permeabilities which are approximately P(CO2 )congruent to 2 cm/s, and P(H2O)congruent to 0.002 cm/s and P(HCO3-)co ngruent to 0.00015 cm/s (values from the literature). We found that th e numerical simulation is affected most by PHCO3-. The influence of th e other permeabilities is at least ten times less. Therefore within th e range of normal literature values, PHCO3- is the only permeability t hat has a rate limiting effect on O-18 exchange. This is why, in turn, PHCO3- can be derived from an experimentally determined time course o f mass 46/mass 44 by a fitting procedure. Another crucial parameter th at can be estimated from the experimental results is the intraerythroc ytic carbonic anhydrase activity A(i).