ENZYMES IN MINERALIZING SYSTEMS - STATE-OF-THE-ART

The hallmark of biological mineralization is the precise regulation of mineral deposition in space and time, The cells which produce mineral ized tissues are themselves controlled hy developmental programs and h ormonal signals which result in regulation of gene expression and modu lation of protein function, These signals are transduced into changes in enzyme levels and/or activity, Upon activation, cellular enzymes th en act to synthesize the organic matrix and process it extracellularly , utilize metabolic energy to transport ions from the blood to the mat rix, and to initiate the mineralization cascade. The first enzyme acti vity described in mineralizing tissues was alkaline phosphatase and it is still the best characterized enzyme in the mineralization process, Yet, important questions about the role of this protein remain unansw ered, and it continues to occupy a central focus in mineralized tissue investigation, Other phosphatases, including protein tyrosine phospha tases are important in regulating tyrosine kinase mediated signals, In vestigators have now begun to look closely at several groups of kinase s which are also important for proper mineralization. As peptide hormo nes are important modulators of mineralized tissues, protein kinase A has always been presumed to play a key role in phosphorylating intrace llular proteins, There is also considerable interest in protein kinase C, as well as tyrosine kinases in mineralized tissue signal transduct ion, Another group of kinases important in mineralized tissues are the enzymes which phosphorylate the matrix phosphoproteins. Of these, cas ein kinase II appears to be involved in intracellular and extracellula r protein phosphorylation. Several enzymes present in the pre-minerali zed matrix are thought to be significant in triggering mineralization. Alkaline phosphatase may act at this level, but new data also suggest s that metalloproteases and gelatinases, by modifying or digesting mat rix components, may be important in the initiation of calcification.