Perspectives in Alkaline Phosphatase Research

Gene cloning and site-directed mutagenesis have had a profound effect on alkaline phosphatase research. Four distinct structural genes encoding placental, intestinal, and tissue-nonspecific isoenzymes have been cloned, sequenced, and mapped to human chromosomes. Differences in properties between the respective gene products are due to variations in primary structure involving only one, or a few, key amino acid residues. Recognition that alkaline phosphatase belongs to the category of molecules that are localized to cell membranes through a COOH-terminal glycan-phosphatidylinositol anchor provides a basis for understanding the generation of isoforms observed in plasma in disease. Isoforms produced by differential cleavage or preservation of the glycan-phosphatidylinositol anchor may offer new correlations with disease that are of diagnostic value. However, a more important contribution of alkaline phosphatase research to clinical chemistry may prove to be an increased understanding of disease processes at the molecular level.