II. Inhibition of Leukocyte Alkaline Phosphatase by Amino Acids and Its Reversal by Zinc’

The activity of leukocyte alkaline phosphatase is inhibited by a number of amino acids, most notably cysteine and histidine. The mechanism of this inhibition involves chelation of Zn2+ by the amino acids, as indicated by the complete reversal of the inhibition by added Zn2+. The concentrations of amino acids and Zn2 required to affect the enzyme activity are such that their interaction might represent an in vivo mechanism for the control of leukocyte alkaline phosphatase activity. Additional Keyphrases physiological control of phosphatase activity #{149}Zn2 cofactor #{149}chelation by amino acids A previous communication described the in-hibition of leukocyte alkaline phosphatase (or-thophosphoric monoester phosphohydrolase, EC 3.1.3.1) by glycine, and outlined an assay which circumvented this inhibition (1). A similar in-hibition of rat bone phosphatase and rat in-testinal phosphatase by glycine has been re-ported (2), although the mechanism of this in-hibition remains obscure. Because zinc is known to activate leukocyte alkaline phosphatase (3) and amino acids will bind this ion (4), we wished to determine the effects of Zn2 on the inhibition by amino acids of leukocyte alkaline phosphatase. Here, we demonstrate that a number of amino acids will inhibit leukocyte alkaline phosphatase, and further show that this inhibition may be completely overcome by adding exogenous ZnS+. Materials and Methods Leukocytes were isolated and disrupted by sonication as previously described (1). Both normal controls and persons with acute infectio