AbstractThe effect of Mn2+, a divalent metal, on the enzyme K+‐p‐nitrophenyl phosphatase (K+‐PNPPase) was studied in rat brain. The metal was found to be a moderate inhibitor of the enzyme, with an I50of approximately 480 μM. The inhibition was pH dependent, but not temperature dependent. On measurement of the inhibition with varying concentrations of PNPP (1–5 mM), the I50value remained constant. However, when the inhibition was measured with K+(5–20 mM), the lso value increased from 130 μMto 490 μM, suggesting that K+antagonized the effect of Mn2+. In kinetic studies, Mn2+inhibited the enzyme in a non‐competitive manner with respect to PNPP. TheKmremained constant (2.9), but theFmaxwas decreased from 5.0 to 1.6. However, with respect to K+, the inhibition was competitive, as the concentration for half maximal activation (K0.5) increased from 1.3 to 8.9 mmol I−1with 1 mMof MnCl2, suggesting that the apparent affinity of K+for the enzyme was decreased. The apparentVmaxwas not affected. The degree of cooperativity (n) measured as the slope of the Hill plot remained unaltered (1.9 ± 0.2) over the entire concentration ran