Regulation of oxidative phosphorylation through each-step activation (ESA): Evidences from computer modeling. (May 2017)

• Record Type: Journal Article
• Authors: Korzeniewski, Bernard
• Is Part Of: Progress in biophysics and molecular biology. Volume 125(2017)
• Page Start: 1
• Page End: 23
• Publication Date: 2017-05
• Subjects: Metabolism regulation -- Energy metabolism -- Skeletal muscle -- Heart -- Computer model -- Work transitions; ADH relative activation of NADH supply (times) (increase in its rate constant) in relation to rest -- AGL relative activation of glycolysis (times) (increase in its rate constant) in relation to rest -- AOX relative activation of OXPHOS (times) (increase in rate constants of all its complexes) in relation to rest -- AUT relative activation of ATP usage (times) (increase in its rate constant) in relation to rest -- AK adenylate kinase -- CK creatine kinase -- ESA each-step activation -- OXPHOS oxidative phosphorylation -- t1/2on half-transition time during on-transient -- t1/2off half-transition time during off-transient -- t(ON)DH characteristic activation time of NADH supply during on-transient -- t(ON)GL characteristic activation time of glycolysis during on-transient -- t(ON)OX characteristic activation time of OXPHOS during on-transient -- t(OFF)DH characteristic inactivation time of NADH supply during off-transient -- t(OFF)GL characteristic inactivation time of glycolysis during off-transient -- t(OFF)OX characteristic inactivation (decay) time of OXPHOS during off-transient -- vCK rate of ATP synthesis by CK -- vGL rate of ATP synthesis by anaerobic glycolysis -- vOX rate of ATP synthesis by OXPHOS (+aerobic glycolysis) -- vUT the rate of ATP utilization -- V˙O2 rate of oxygen consumption; Biophysics -- Periodicals; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular Biology -- Periodicals; Biophysique -- Périodiques; Biochimie -- Périodiques; 571.4
• DOI: 10.1016/j.pbiomolbio.2016.12.001
• Languages: English
• ISSNs: 0079-6107

Abstract

Abstract: The mechanisms responsible for matching of the highly varying ATP demand by ATP supply in muscle are of primary importance for pure science, sport science and medicine. According to the traditional opinion ATP supply is activated by elevated ADP and Pi resulting from ATP hydrolysis during intensive work. Theoretical studies using the computer model of oxidative phosphorylation (OXPHOS) and the entire cell bioenergetic system developed by the author and co-workers lead to the each-step-activation (ESA) mechanism of the regulation of the system in skeletal muscle, heart and other tissues during work transitions. According to ESA not only ATP usage, but also all OXPHOS complexes (complex I, complex III, complex IV, ATP synthase, ATP/ADP carrier, Pi carrier), NADH supply block and (anaerobic) glycolysis are directly activated by some cytosolic factor/mechanism during rest- or low-to-high work transitions. ESA conception results from large increase in oxygen consumption ( V ˙ O2 ) and ATP turnover flux accompanied by only moderate or no changes in metabolite (ADP, Pi, PCr, NADH) concentrations during work transitions in skeletal muscle and heart and from the uniform distribution among OXPHOS complexes of the metabolic control over V ˙ O2, as defined within Metabolic Control Analysis. Several theoretical studies carried out using the discussed computer model of the cell bioenergetic system are overviewed. It is demonstrated that this model, involving the ESA mechanism, is able to explain numerous, apparently unrelated to each other, properties of the system.