PRPP SYNTHETASE SUPERACTIVITY IN LYMPHOBLAST LINES: 11

Abstract

Superactivity of PRPP synthetase (PS) is an X chromosome-linked disorder associated with gout and uric acid overproduction. Fibroblasts from affected males show PS superactivity and increased rates of PRPP and purine nucleotide synthesis. Kinetic aberrations underlying PS superactivity include: catalytic defects; regulatory defects; substrate (ribose-5-P) binding defects; and combined catalytic and regulatory defects.We studied PS in B lymphoblasts derived from blood lymphocytes (PBL) of 6 males whose fibroblasts express the 4 classes of PS superactivity. Neither excessive PS activity nor increased rates of PRPP or purine synthesis were found in lymphoblasts from 3 patients with catalytic defects in fibroblasts, despite PS superactivity in PBL from these patients. Catalytic superactivity was also absent in lymphoblasts from a patient with combined defects in fibroblast PS. These cells and cells from 2 other patients expressed the specific regulatory and substrate binding defects found in fibroblast PS from the respective patients and also showed increased rates of PRPP and purine synthesis.Immunoreactive PS differed <20% among lymphoblast lines, and PS absolute specific activities were those of normal fibroblast PS. Thus, neither reduced levels of mutant PS nor activation of normal PS explained selective expression of PS superactivity in lymphoblasts. Altered electrophoretic mobilities and thermal stabilities, found with some catalytically superactive fibroblast PS, were absent in lymphoblasts from the respective patients. The basis of selective expression of PS superactivity remains to be determined.