Model of 2,3-bisphosphoglycerate metabolism in the human erythrocyte based on detailed enzyme kinetic equations1 : in vivo kinetic characterization of 2,3-bisphosphoglycerate synthase/phosphatase using 13C and 31P NMR

This is the first in a series of three papers [see also Mulquiney and Kuchel (1999) Biochem. J. 342, 579–594; Mulquiney and Kuchel (1999) Biochem. J. 342, 595–602] that present a detailed mathematical model of erythrocyte metabolism which explains the regulation and control of 2,3-bisphosphoglycerate (2,3-BPG) metabolism. 2,3-BPG is a modulator of haemoglobin oxygen affinity and hence plays an important role in blood oxygen transport and delivery. This paper presents an in ŠiŠo kinetic characterization of 2,3-BPG synthase}phosphatase (BPGS}P), the enzyme that catalyses both the synthesis and degradation of 2,3-BPG. Much previous work had indicated that the behaviour of this enzyme in Šitro is markedly different from that in ŠiŠo. "$C and $"P NMR were used to monitor the time courses of selected metabolites when erythrocytes were incubated with or without [U-"$C]glucose. Simulations of the experimental time courses were then made. By iteratively changing the parameters of the BPGS}P part of the model until a good match between the NMR-derived data and simulations were achieved, it was possible