Evidence that three structural genes code for human alkaline phosphatases

Abstract

The number of structural gene loci that code for the different molecular forms of human alkaline phosphatase is unknown. Physical properties of the enzymes, immunological data, chemical inhibition and genetic studies suggest that at least three structural genes¹ are involved: one coding for alkaline phosphatase from placenta, another for the enzyme from intestine, and one or more for the enzymes from liver, kidney and bone. Badger and Sussman² have shown that alkaline phosphatases from human liver and placenta are products of different structural genes, and Greene and Sussman³ have shown that alkaline phosphatase from a metastasised bronchogenic carcinoma was nearly identical to the enzyme from placenta. However, other tumour-associated alkaline phosphatases and the enzymes from normal tissues other than placenta and liver have not been identified by conclusive structural criteria⁴, and thus it is not known whether these onco-alkaline phosphatases represent ectopic production or unusual post-translational modification of the enzymes found in normal tissues. We present here, using a sensitive peptide-mapping technique⁵, structural evidence that the enzyme forms from liver, kidney and serum from a patient with Paget's disease of bone (osteitis def ormans) are products of the same structural gene and can be easily distinguished from either the intestinal or placental isoenzymes. The technique seems to be useful for the classification of tumour-associated alkaline phosphatases on a structural basis.