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Interpretation of extracted parameters is subject to multiple caveats. Here we analyze the impact of temperature variations of underlying activation or Eyring parameters and of temperature\u2010dependent contributions to overall rates from steps other than a rate\u2010limiting chemical step. Linear Arrhenius\/Eyring behavior can still be observed when the underlying activation energy  or enthalpy  and entropy  vary with temperature. Modest variations\u2014of the order of an H\u2010bond energy over 60\u00b0C\u2014lead to large fractional deviations of ,  and  values derived from linear fits from their underlying values and to deviations of Arrhenius prefactors  by orders of magnitude. In a family of related enzymes with similar activation free energies , small differences in temperature\u2010dependent contributions to overall rates will lead to apparent enthalpy\u2013entropy compensation and may scramble enzyme ordering based on  or . Similar considerations apply to interpretation of van \u2018t Hoff plots of equilibrium measurements and related observations of enthalpy\u2013entropy compensation. For enzymes exhibiting negative curvature and maximum rates well below the unfolding temperature, fits assuming  and  are connected by a negative heat capacity  yield physically implausible values, suggesting the importance of other contributions to observed behavior. Complementary methods including pre\u2010steady\u2010state kinetics, kinetic isotope effect and viscosity\u2010dependence measurements, multi\u2010temperature static and time\u2010resolved atomic\u2010resolution structural studies, and simulations should play a key role in quantitatively interpreting temperature\u2010dependent kinetic and equilibrium data from enzymatic systems.<\/jats:p>","DOI":"10.1002\/pro.70722","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T14:35:25Z","timestamp":1784903725000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Activation parameters, enthalpy\u2013entropy compensation and the temperature\u2010dependent activity of enzymes"],"prefix":"10.1002","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5540-916X","authenticated-orcid":false,"given":"Matthew J.","family":"McLeod","sequence":"first","affiliation":[{"name":"Department of 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