ABSTRACT. COL product~on in aerobic bacteria was modeled from the time-courses of the 1x1 vitl-o activity of isocitrate dehydrogenase (IDH), bacterial protein, and the concentrat~on of the carbon source in the cultures. The model was based on the concept of bisubstrate control of the IDH reaction throughout the exponential, steady-state, and senescent phases of the cultures In the exponential phase, the measured rates of CO, production and the In vltro IDH actlvity were closely coupled, but in the senescent phase, they became uncoupled The In vltro IDH actlvity remained hlgh even after the culture's carbon source was exhausted, while the CO, production fell to low levels Based on the hypothesis that thls uncoupling was caused by ~n t e r n a l substrate limitation, 2 mathematical models incorporating a bisubstrate enzyme kinetics algorithm were constructed and tested. The models predicted the rate of CO2 production throughout the different phases of the cultures w~t h a n r2 greater than 0.84.
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