Journal article
Creatine Kinase Equilibration and ?GATP over an Extended Range of Physiological Conditions: Implications for Cellular Energetics, Signaling, and Muscle Performance
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v 24(17), 13244
Sep 2023
PMID: 37686064
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
In this report, we establish a straightforward method for estimating the equilibrium constant for the creatine kinase reaction (CK K-eq) over wide but physiologically and experimentally relevant ranges of pH, Mg2+ and temperature. Our empirical formula for CK K-eq 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 ?G(ATP), necessitating the reinvestigation of previously reported ADP- and ?G(ATP)-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 ?G(ATP) 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.
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Details
- Title
- Creatine Kinase Equilibration and ?GATP over an Extended Range of Physiological Conditions: Implications for Cellular Energetics, Signaling, and Muscle Performance
- Publication Details
- INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v 24(17), 13244
- Publisher
- MDPI; BASEL
- Grant note
- This publication is dedicated to the memory of two outstanding scientists who were also exceptional mentors, collaborators, and friends. To Martin J. Kushmerick, whose dedication to the field of bioenergetics of muscle inspired the authors to initiate this project and further inspired several of the authors of this Special Issue on Structural, Chemical, and Energetic Signals in Striated Muscle Function; and to Albert M. Gordon, whose careful studies on the biophysics of striated muscle contraction and its regulation by Ca2+ were essential to our ability to generate the solutions for this study and provided inspiration for reinterpretation of previously published mechanics data. The authors wish to gratefully acknowledge the excellent technical assistance of Martha Mathiason and Robin Mondares for creating the software to calculate solution compositions based on available binding data and Gopal Ramanchandran for generating the families of solutions necessary for each condition. The use of a Millennium High Performance Chromatograph in the University of Washington laboratory of Kenneth A. Krohn is greatly appreciated. The authors thank Jason N. Bazil, Gregory D. Fink, and Ronald A. Meyer for careful reading and critical comments on the manuscript.
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Drexel University
- Web of Science ID
- WOS:001064113400001
- Scopus ID
- 2-s2.0-85170201523
- Other Identifier
- 991021860716004721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Chemistry, Multidisciplinary