This study seeks to determine the molecular bases of certain inherited aldose-ketose isomerase deficiency diseases. These genetic disorders are transmitted as autosomal recessives and result from the synthesis of abnormal isomerases. The enzymes will be isolated in homogeneous form by affinity chromatographic techniques and compared with the normal human isomerases. Peptide fingerprinting, amino acid sequencing, and immunological studies of the aberrant enzymes will be correlated with their altered catalytic properties. The genetic and apogenetic mechanisms which regulate the expression of the isomerases will be explored by a variety of physical, chemical and catalytic methods including analytical ultracentrifugation, subunit and isoenzyme hybridization, electrophoresis and electrofocusing. Structural studies on the normal and abnormal enzymes will establish the sequences of the active center, the contact sites involved in subunit-subunit and protein-protein interactions, and the sites of the genetic lesions. Metabolic studies will ascertain the primary and secondary consequences of these metabolic blocks.
NIH ExPorter
NIH ExPorter