{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T05:05:50Z","timestamp":1789967150153,"version":"4.0.1"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Despite animal research of cellular and systemic acidosis for more than 100 years, there is no dominant evidence-based understanding of the cause of metabolic acidosis. Embedded in this crisis state is the understanding that the hydrogen ion (H\n                      <jats:sup>+<\/jats:sup>\n                      ) involved in some chemical reactions, either as a substrate or product (H\n                      <jats:sup>+<\/jats:sup>\n                      exchange (H\n                      <jats:sup>+<\/jats:sup>\n                      <jats:sub>e<\/jats:sub>\n                      )), does not change the pH of biological solutions. This research documents the direct roles of the H\n                      <jats:sup>+<\/jats:sup>\n                      <jats:sub>e<\/jats:sub>\n                      of a selection of non-glycolytic cytosolic chemical reactions in changing the pH of an unbuffered aqueous solution.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Reagents were prepared using deionized water, substrates at known concentrations, enzymes and needed activator chemicals. The chemical reactions studied were creatine kinase (CKase) (to ATP and CrP), ATPase, hexokinase (HKase), and glucose-6-phosphate dehydrogenase (G\n                      <jats:sub>6<\/jats:sub>\n                      PDHase). Each reaction was started by addition of the enzyme, and reagent pH was measured intermittently using a pH electrode. Samples of reagent (200 \u03bcL) were acquired for product measurement by spectrophotometry.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Results are presented as start pH:end pH; [Product], mmol\u0387L\n                      <jats:sup>-1<\/jats:sup>\n                      ; pH:[Product] slope, pH.mmol\n                      <jats:sup>-1<\/jats:sup>\n                      .L\n                      <jats:sup>-1<\/jats:sup>\n                      : CKase to ATP (7.49:9.51; [1.95]; 1.289); CKase to CrP (8.29:7.89; [0.64]; -1.35); ATPase (8.94:8.23; [0.84]; -0.9385); HKase (8.59:6.55; [2.36];-1.596), G\n                      <jats:sub>6<\/jats:sub>\n                      PDHase (7.53:6.89; [1.46]; -0.8006). All chemical reactions that produced carboxylic acids did so as anions, and all resulted in pH responses consistent with the role of the H\n                      <jats:sup>+<\/jats:sup>\n                      as a substrate or product. The sequencing or summing of the CKase, ATPase, HKase and G6PDHase reactions revealed potential for summative computational modelling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The evidence opposes traditional theories as the sole cause of cellular or systemic acidosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmolb.2026.1816622","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T04:29:32Z","timestamp":1789964972000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["H+ exchange and pH profiling of select non-glycolytic cytosolic phosphate transfer and oxidation\u2013reduction reactions"],"prefix":"10.3389","volume":"13","author":[{"given":"Robert","family":"Robergs","sequence":"first","affiliation":[{"name":"Faculty of Health Studies, Jan Evangelista Purkyn\u00e9 University","place":["\u00dast\u00ednad Labem, Czech Republic"]},{"name":"Department of Physiology, Faculty of Medicine, Charles University","place":["Pilsen, Czech Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Nalos","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Medicine, Pilsen Hospital and Charles University","place":["Pilsen, Czech Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petr","family":"Kelbich","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Laboratory Diagnostics, Faculty of Health Studies, Jan Evangelista Purkyn\u00e9 University and Masaryk Hospital in \u00dast\u00ednad Labem","place":["\u00dast\u00ednad Labem, Czech Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adela","family":"Jizerov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Laboratory Diagnostics, Faculty of Health Studies, Jan Evangelista Purkyn\u00e9 University and Masaryk Hospital in \u00dast\u00ednad Labem","place":["\u00dast\u00ednad Labem, Czech Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"Mervartov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Environmental Chemistry, Jan Evangelista Purkyn\u00e9 University","place":["\u00dast\u00ednad Labem, Czech Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Vostr\u00fd","sequence":"additional","affiliation":[{"name":"Faculty of Health Studies, Jan Evangelista Purkyn\u00e9 University","place":["\u00dast\u00ednad Labem, Czech Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milan","family":"\u0160tengl","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Charles University","place":["Pilsen, Czech Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vaclav","family":"Babu\u0161ka","sequence":"additional","affiliation":[{"name":"Department of Medical Chemistry and Biochemistry, Faculty of Medicine, Charles University","place":["Pilsen, Czech Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2038","DOI":"10.7860\/JCDR\/2013\/5230.3400","article-title":"History of medical understanding and misunderstanding of acid base balance","volume":"7","author":"Aiken","year":"2013","journal-title":"J. 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