PKU AND OTHER DISEASES CAUSED BY DEFECTS IN BIOPTERIN DEPENDENT ENZYMES

双功能蛋白的位点特异性突变研究

Site-specific mutational studies of the bifunctional protein carbinolamine dehydratase/DCoH, whose deficiency is a cause of hyperphenylalaninemia, have shown that the two activities can be selectively knocked out. A new activity that very significantly increases the levels of active phenylalanine hydroxylase in tissue culture has been demonstrated for carbinolamine/dihydratase. Using recombinant DNA techniques, we have co-engineered several naturally-occuring mutants of phenylalanine hydroxylase known to cause phenylketonuria and have carried out a preliminary kinetic characterization of these mutants. Epidermal keratinocytes have been shown to have low, but detectable levels of carbinolamine dehydratase.