Biochemistry 2011, 50, 663–671 663 DOI: 10.1021/bi101523x
Stabilization of the Predominant Disease-Causing Aldolase Variant (A149P) with Zwitterionic Osmolytes† Jack D. Stopa,‡ Sushil Chandani,§ and Dean R. Tolan*,‡,§ ‡
Program in Molecular and Cellular Biology and Biochemistry and §Department of Biology, Boston University, 5 Cummington Street, Boston, Massachusetts 02215, United States Received September 19, 2010; Revised Manuscript Received December 15, 2010
ABSTRACT:
Hereditary fructose intolerance (HFI) is a disease of carbohydrate metabolism that can result in hyperuricemia, hypoglycemia, liver and kidney failure, coma, and death. Currently, the only treatment for HFI is a strict fructose-free diet. HFI arises from aldolase B deficiency, and the most predominant HFI mutation is an alanine to proline substitution at position 149 (A149P). The resulting aldolase B with the A149P substitution (AP-aldolase) has activity that is
