Substitution of Mg 2+ cofactor with Ca 2+ disrupts positive cooperativity in F 1 F O -ATP(hydrol)ase catalysis.
Level 5 - mechanism / opinion, no new human data
In vitro biochemical study of enzyme kinetics (bench research)
PubMed 41520859 · doi:10.1016/j.bbabio.2025.149580
What was done
The authors evaluated the kinetic behavior of mitochondrial F1FO-ATPase during ATP hydrolysis in the presence of its physiological cofactor (Mg2+) versus Ca2+, including the inhibitory mechanism of Ca2+ on Mg2+-dependent activity.
What was found
Mg2+-dependent F1FO-ATPase displayed positive cooperativity in ATP hydrolysis with a Hill coefficient (nHi) of 2.01 ± 0.21. In contrast, Ca2+-dependent activity exhibited Michaelian kinetics with an nHi of 1.41 ± 0.06. Ca2+ acted as an uncompetitive inhibitor of Mg2+-dependent ATP hydrolysis.
Why it matters
The findings clarify how divalent cation availability alters F1FO-ATPase catalytic mechanisms and allosteric cooperativity, providing insight into mitochondrial enzymatic behavior under physiological versus pathological calcium-overload conditions.
Limits
The study is an isolated in vitro biochemical kinetic assay; the abstract does not report the biological source or species of the enzyme preparation, reaction conditions (such as pH, temperature, or specific inhibitor concentrations), or whether these kinetic alterations occur in intact cellular or mitochondrial models.
Cited by
- supports ATP synthesis in human cells cannot occur without magnesium.