The limitations of the efficiency of ammonium-neutralizing erythrocyte-bioreactors based on glutamate dehydrogenase and alanine aminotransferase reactions were analyzed using a mathematical model. At low pyruvate concentrations in the external medium (below about 0.3 mM), the main limiting factor is the rate of pyruvate influx into the erythrocyte from the outside, and at higher concentrations, it is the disappearance of a steady state in glycolysis if the rate of ammonium processing is higher than the critical value (about 12 mM/h). This rate corresponds to different values of glutamate dehydrogenase activity at different concentrations of pyruvate in plasma. Oxidation of reduced nicotinamide adenine dinucleotide phosphate (NADPH) by glutamate dehydrogenase decreases the fraction of NADPH in the constant pool of nicotinamide adenine dinucleotide phosphates (NADP + NADPH). This, in turn, activates the pentose phosphate pathway, where NADP reduces to NADPH. Due to the increase in flux through the pentose phosphate pathway, stabilization of the ATP concentration becomes impossible; its value increases until almost the entire pool of adenylates transforms into the ATP form. As the pool of adenylates is constant, the ADP concentration decreases dramatically. This slows the pyruvate kinase reaction, leading to the disappearance of the steady state in glycolysis.

中文翻译：

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内置代谢途径对中和铵的红细胞-生物反应器代谢的影响的理论分析

使用数学模型分析了基于谷氨酸脱氢酶和丙氨酸氨基转移酶反应的铵中和性红细胞生物反应器效率的局限性。在外部培养基中丙酮酸浓度较低（低于约0.3 mM）时，主要限制因素是丙酮酸从外部流入红血球的速率，而在较高浓度下，如果丙酮酸速率达到这一水平，则是糖酵解中稳态的消失铵处理量高于临界值（约12 mM / h）。该速率对应于血浆中不同丙酮酸浓度下的谷氨酸脱氢酶活性的不同值。谷氨酸脱氢酶氧化还原的烟酰胺腺嘌呤二核苷酸磷酸（NADPH）会减少烟酰胺腺嘌呤二核苷酸磷酸（NADP + NADPH）恒定池中NADPH的比例。反过来，这激活了戊糖磷酸途径，其中NADP还原为NADPH。由于通过戊糖磷酸途径的通量增加，因此无法稳定ATP浓度。直到几乎所有的腺苷酸池转化为ATP形式，其值才会增加。由于腺苷酸池是恒定的，因此ADP浓度急剧下降。这减慢了丙酮酸激酶反应，导致糖酵解中稳态的消失。由于通过戊糖磷酸途径的通量增加，因此无法稳定ATP浓度。直到几乎所有的腺苷酸池转化为ATP形式，其值才会增加。由于腺苷酸池是恒定的，因此ADP浓度急剧下降。这减慢了丙酮酸激酶反应，导致糖酵解中稳态的消失。由于通过戊糖磷酸途径的通量增加，因此无法稳定ATP浓度。直到几乎所有的腺苷酸池转化为ATP形式，其值才会增加。由于腺苷酸池是恒定的，因此ADP浓度急剧下降。这减慢了丙酮酸激酶反应，导致糖酵解中稳态的消失。