期刊
FREE RADICAL RESEARCH
卷 41, 期 11, 页码 1201-1211出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/10715760701625075
关键词
glutathione; glutathione peroxidase; hydrogen peroxide; mathematical modelling; kinetics
资金
- NCI NIH HHS [R01 CA084462, CA-84462, R01 CA084462-04, P01 CA066081-069001, P01 CA066081, P01 CA066081-020003, P01 CA066081-060003, CA-66081] Funding Source: Medline
Although its concentration is generally not known, glutathione peroxidase-1 (GPx-1) is a key enzyme in the removal of hydrogen peroxide (H2O2) in biological systems. Extrapolating from kinetic results obtained in vitro using dilute, homogenous buffered solutions, it is generally accepted that the rate of elimination of H2O2 in vivo by GPx is independent of glutathione concentration (GSH). To examine this doctrine, a mathematical analysis of a kinetic model for the removal of H2O2 by GPx was undertaken to determine how the reaction species (H2O2, GSH, and GPx-1) influence the rate of removal of H2O2. Using both the traditional kinetic rate law approximation (classical model) and the generalized kinetic expression, the results show that the rate of removal of H2O2 increases with initial GPx, as expected, but is a function of both GPX(r) and GSH when the initial GPXr is less than H2O2. This simulation is supported by the biological observations of Li et al.. Using genetically altered human glioma cells in in vitro cell culture and in an in vivo tumour model, they inferred that the rate of removal of H2O2 was a direct function of GPx activity x GSH (effective GPx activity). The predicted cellular average GPXr and H2O2 for their study are approximately GPx(r) <= 1 mu m and H2O2 approximate to 5 mu m based on available rate constants and an estimation of GSH. It was also found that results from the accepted kinetic rate law approximation significantly deviated from those obtained from the more generalized model in many cases that may be of physiological importance.
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