Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Creatine Kinase Equilibration and ΔGATP Over an Extended Range of Physiological Conditions: Implications for Cellular Energetics, Signaling and Muscle Performance

Robert W. Wiseman
ORCID logo ,
Caleb M. Brown
ORCID logo ,
Thomas W. Beck
ORCID logo ,
Jeffrey J. Brault
ORCID logo ,
Tyler R. Reinoso
ORCID logo ,
Yun Shi
,
P. Bryant Chase
* ORCID logo
Version 1 : Received: 22 August 2023 / Approved: 23 August 2023 / Online: 24 August 2023 (09:50:53 CEST)

A peer-reviewed article of this Preprint also exists.

Wiseman, R.W.; Brown, C.M.; Beck, T.W.; Brault, J.J.; Reinoso, T.R.; Shi, Y.; Chase, P.B. Creatine Kinase Equilibration and ΔGATP over an Extended Range of Physiological Conditions: Implications for Cellular Energetics, Signaling, and Muscle Performance. Int. J. Mol. Sci. 2023, 24, 13244. Wiseman, R.W.; Brown, C.M.; Beck, T.W.; Brault, J.J.; Reinoso, T.R.; Shi, Y.; Chase, P.B. Creatine Kinase Equilibration and ΔGATP over an Extended Range of Physiological Conditions: Implications for Cellular Energetics, Signaling, and Muscle Performance. Int. J. Mol. Sci. 2023, 24, 13244.

Abstract

In this report, we establish a straightforward method for estimating the equilibrium constant for the CK reaction 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 could estimate ΔGATP. Application to actomyosin force generation in muscle provides support for the hypothesis that, when [Pi] varies but not when pH is altered, 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 for the role of submicromolar ADP in force generation.

Keywords

skeletal muscle; actomyosin ATPase; ADP; temperature; cytoplasmic magnesium ion concentration, cytoplasmic pH; inorganic phosphate, Pi; isometric force generation

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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