Calcium ions as catalysts: Quantum chemical and experimental study of creatine cyclization to creatinine.
Level 5 - mechanism / opinion, no new human data
In vitro bench and computational chemistry study without human data
PubMed 41723981 · doi:10.1016/j.bbrc.2026.153469
What was done
The authors modeled the non-enzymatic cyclization of creatine to creatinine using quantum chemical calculations (DFT/MN15/Def2-TZVP with PCM solvent modeling) across intramolecular conditions, with water, and in the presence of Ca2+, K+, and Mg2+ ions. Theoretical findings were tested experimentally using in situ UV-Vis microfluidimetry.
What was found
DFT calculations indicated that Ca2+ coordinates water molecules near the reaction center, lowering the energy barrier for cyclization and water elimination steps, while Mg2+ acts as a competitive inhibitor preventing this barrier reduction. In experimental testing, Ca2+ increased the creatine-to-creatinine conversion rate by 13%. Absolute energy barrier metrics, reaction rates for other ions, and statistical variance were not reported in the abstract.
Why it matters
This study provides a molecular mechanism explaining how elevated intracellular calcium during myocardial ischemia might accelerate the loss of the cardiac energy carrier creatine, suggesting magnesium may play a protective role.
Limits
The study is restricted to in vitro microfluidimetry and in silico modeling; it lacks validation in live cardiomyocytes, intact cardiac tissue, or animal models. Exact ion concentrations, reaction kinetics, and statistical parameters are omitted from the abstract.
Cited by
- supports Creatine in muscle is non-enzymatically metabolized into creatinine.