The sodium ion is generally not considered a specific cofactor because one has yet to demonstrate an enzyme whose catalysis depends strictly on sodium ions. Sodium-activated enzymes often respond to surrogate metal cofactors such as Li+ or even divalent cations. The magnesium ion is required by a large number of enzymes referred to as kinases, enzymes that transfer the terminal phosphate group of ATP to a substrate. Kinase enzymes figure prominently in many biochemical pathways such as glyco-lysis (hexokinase, fructose-6-phosphate kinase, pyruvate kinase), hormone responses mediated by cyclic AMP, cell signaling, and regulation of cell division. The potassium ion is a specific cofactor for pyruvate kinase in the glycolysis pathway. Both potassium and magnesium form no permanent bonds with their respective enzymes and hence act more in the capacity of activators.

Although chromium, tin, arsenic and strontium have been postulated by some investigators to be essential for optimal growth and health of organisms, as well as having a positive influence on biological systems, cofactor functions for their ions have not been assigned because specific enzymes that may require them for activity have not been found.

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