Immunochemical studies of human placental-type variants of alkaline phosphatase. Structural differences between the "Nagao isoenzyme" and the placental "D-variant".
Hyperimmune antisera raised against the rare FD and SD phenotypes of human placental alkaline phosphatase and the related cancer-associated Nagao isoenzyme were exhaustively absorbed with the common SS and FF phenotype enzymes conjugated to Sepharose. The antibodies so obtained had one of three specificities, determined by testing all the common phenotypes of placental alkaline phosphatase, the rare FD, SD and S-17 phenotypes, and five samples of purified cancer patient enzymes: (I) antibodies reactive with the S, D and I variant enzymes, but not with the F, 17 or Nagao enzymes; (II) antibodies reactive with the F, 17 and Nagao enzymes, but not with the S, D, and I variant enzymes; and (III) antibodies reactive with the D, 17 and Nagao enzymes and not with the S, F or I variant enzymes. Based on these data, and on the information obtained from biochemical characterization, it is argued that the Nagao isoenzyme and the D-variant are closely related but distinct enzymes. We propose a hypothetical scheme for the divergence of these two enzymes from a common ancestral gene product. In this scheme, an ancestral gene duplication resulted in two isoenzymes, one of which is completely specific to the placenta, and one of which (the "Nagao isoenzyme") has an unknown normal tissue localization, but is found in some cases of cancer. We use the term "syn-placental" to describe this latter isoenzyme, reflecting its close structural relationship to the placental isoenzyme.
D000469:Alkaline Phosphatase / Q000235:genetics* / Q000276:immunology; D000936:Antigen-Antibody Complex; D005260:Female; D014644:Genetic Variation; D006801:Humans; D007106:Immune Sera; D007074:Immunoglobulin G; D007527:Isoenzymes / Q000235:genetics; D007700:Kinetics; D010641:Phenotype; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy
D000936:Antigen-Antibody Complex; D007106:Immune Sera; D007074:Immunoglobulin G; D007527:Isoenzymes; D000469:Alkaline Phosphatase