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- Title
Creatine Kinase Equilibration and ΔG ATP over an Extended Range of Physiological Conditions: Implications for Cellular Energetics, Signaling, and Muscle Performance.
- Authors
Wiseman, Robert Woodbury; Brown, Caleb Micah; Beck, Thomas Wesley; Brault, Jeffrey John; Reinoso, Tyler Robert; Shi, Yun; Chase, Prescott Bryant
- Abstract
In this report, we establish a straightforward method for estimating the equilibrium constant for the creatine kinase reaction (CK Keq″) over wide but physiologically and experimentally relevant ranges of pH, Mg2+ and temperature. Our empirical formula for CK Keq″ is based on experimental measurements. It can be used to estimate [ADP] when [ADP] is below the resolution of experimental measurements, a typical situation because [ADP] is on the order of micromolar concentrations in living cells and may be much lower in many in vitro experiments. Accurate prediction of [ADP] is essential for in vivo studies of cellular energetics and metabolism and for in vitro studies of ATP-dependent enzyme function under near-physiological conditions. With [ADP], we were able to obtain improved estimates of ΔGATP, necessitating the reinvestigation of previously reported ADP- and ΔGATP-dependent processes. Application to actomyosin force generation in muscle provides support for the hypothesis that, when [Pi] varies and pH is not altered, the maximum Ca2+-activated isometric force depends on ΔGATP in both living and permeabilized muscle preparations. Further analysis of the pH studies introduces a novel hypothesis around the role of submicromolar ADP in force generation.
- Subjects
MYOSIN; SIGNALS &; signaling; ACTOMYOSIN; IN vivo studies; IN vitro studies; ADENOSINE diphosphate
- Publication
International Journal of Molecular Sciences, 2023, Vol 24, Issue 17, p13244
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms241713244