Inhibition of alkaline phosphatase by cysteine and its analogues.

Abstract

Summary 1. A comparison of the inhibition of human-kidney alkaline phosphatase (orthophosphoric monoester phosphohydrolase, EC 3.1.3.1) by cysteine and structurally related compounds shows that two main groups of inhibitors can be distinguished: (a) analogues with free amino and sulfhydryl groups are good inhibitors, (b) analogues with blocked amino or sulfhydryl groups and compounds lacking these groups are poor inhibitors. 2. Studies on the effect of pH on the inhibition reveal that the inhibiting species must have the amino and sulfhydryl group in their basic form. 3. The results indicate that cysteine inhibits alkaline phosphatase by chelation of the Zn atom at the active site of the enzyme. This inhibition seems to be the result of a chelation in situ rather than a removal of the metal from the apoenzyme. 4. Alkaline phosphatase preparations from different tissues, cell cultures and Escherichia coli are all inhibited by the same concentration of L -cysteine.