ALKALINE-PHOSPHATASE - PLACENTAL AND TISSUE-NONSPECIFIC ISOENZYMES HYDROLYZE PHOSPHOETHANOLAMINE, INORGANIC PYROPHOSPHATE, AND PYRIDOXAL 5'-PHOSPHATE - SUBSTRATE ACCUMULATION IN CARRIERS OF HYPOPHOSPHATASIA CORRECTS DURING PREGNANCY

Hypophosphatasia features selective deficiency of activity of the tiss ue-non-specific (liver/bone/kidney) alkaline phosphatase (ALP) isoenzy me (TNSALP); placental and intestinal ALP isoenzyme (PALP and IALP, re spectively) activity is not reduced, Three phosphocompounds (phosphoet hanolamine [PEA], inorganic pyrophosphate [PPI], and pyridoxal 5'-phos phate [PLP]) accumulate endogenously and appear, therefore, to be natu ral substrates for TNSALP. Carriers for hypophosphatasia may have decr eased serum ALP activity and elevated substrate levels. To test whethe r human PALP and TNSALP are physiologically active toward the same sub strates, we studied PEA, PPI, and PLP levels during and after pregnanc y in three women who are carriers for hypophosphatasia, Hypophosphatas emia corrected during the third trimester because of PALP in maternal blood, Blood or urine concentrations of PEA, PPI, and PLP diminished s ubstantially during that time. After childbirth, maternal circulating levels of PALP decreased, and PEA, PPi, and PLP levels abruptly increa sed. In serum, unremarkable concentrations of IALP and low levels of T NSALP did not change during the study period, We conclude that PALP, l ike TNSALP, is physiologically active toward PEA, PPI, and PLP in huma ns. We speculate from molecular/crystallographic information, indicati ng significant similarity of structure of the substrate-binding site o f ALPs throughout nature, that all ALP isoenzymes recognize these same three phosphocompound substrates.