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While the utilization of NADH for the reduction of pyruvate to lactate can be mediated via the classical mechanism, the oxidation of lactate (with\/without the uphill reduction of NAD<jats:sup>+<\/jats:sup>) necessitates alternative physiological approaches. The latter pathway occurs via interactive equilibriums involving the enzyme, protons and oxygen or diffusible reactive oxygen species (DROS). Since liver has high DROS, the murburn activity at LDH would enable the cellular system to tide over the unfavorable energy barriers of the forward reaction (~476\u2009kJ\/mol; earlier miscalculated as ~26\u2009kJ\/mole). Further, the new mechanism does not necessitate any \u201csmart decision\u2010making\u201d or sophisticated control by\/of proteins. The DROS\u2010based murburn theory explains the invariant active\u2010site structure of LDH isozymes and their multimeric nature. The theoretical insights, in silico evidence and analyses of literature herein also enrich our understanding of the underpinnings of \u201clactic acidosis\u201d (lowering of physiological pH accompanied by lactate production), Warburg effect (increased lactate production at high pO<jats:sub>2<\/jats:sub> by cancer cells) and approach for cancer therapy.<\/jats:p>","DOI":"10.1002\/jcp.30661","type":"journal-article","created":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T10:34:42Z","timestamp":1639996482000},"page":"1902-1922","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Murburn precepts for lactic\u2010acidosis, Cori cycle, and Warburg effect: Interactive dynamics of dehydrogenases, protons, and oxygen"],"prefix":"10.1002","volume":"237","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4515-994X","authenticated-orcid":false,"given":"Kelath Murali","family":"Manoj","sequence":"first","affiliation":[{"name":"Department of Biochemistry Satyamjayatu: The Science &amp; Ethics Foundation Palakkad Kerala India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5567-0656","authenticated-orcid":false,"given":"Vijay","family":"Nirusimhan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Satyamjayatu: The Science &amp; Ethics Foundation Palakkad Kerala India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4229-0248","authenticated-orcid":false,"given":"Abhinav","family":"Parashar","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Satyamjayatu: The Science &amp; Ethics Foundation Palakkad Kerala India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5019-0947","authenticated-orcid":false,"given":"Jesucastin","family":"Edward","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Satyamjayatu: The Science &amp; Ethics Foundation Palakkad Kerala India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2470-550X","authenticated-orcid":false,"given":"Daniel Andrew","family":"Gideon","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Satyamjayatu: The Science &amp; Ethics Foundation Palakkad Kerala India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,12,20]]},"reference":[{"key":"e_1_2_9_2_1","volume-title":"Thermodynamics of biochemical reactions","author":"Alberty R. 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