Structural and functional analysis of aldolase B mutants related to hereditary fructose intolerance

FEBS Lett. 2002 Nov 6;531(2):152-6. doi: 10.1016/s0014-5793(02)03451-8.


Hereditary fructose intolerance (HFI) is a recessively inherited disorder of carbohydrate metabolism caused by impaired function of human liver aldolase (B isoform). 25 enzyme-impairing mutations have been identified in the aldolase B gene. We have studied the HFI-related mutant recombinant proteins W147R, A149P, A174D, L256P, N334K and delta6ex6 in relation to aldolase B function and structure using kinetic assays and molecular graphics analysis. We found that these mutations affect aldolase B function by decreasing substrate affinity, maximal velocity and/or enzyme stability. Finally, the functional and structural analyses of the non-natural mutant Q354E provide insight into the catalytic role of Arg(303), whose natural mutants are associated to HFI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arginine / physiology
  • Catalysis
  • Fructose Intolerance / genetics
  • Fructose-Bisphosphate Aldolase* / chemistry
  • Fructose-Bisphosphate Aldolase* / genetics
  • Fructose-Bisphosphate Aldolase* / physiology
  • Humans
  • Kinetics
  • Models, Molecular
  • Mutation*
  • Mutation, Missense
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Structure-Activity Relationship


  • Recombinant Proteins
  • Arginine
  • Fructose-Bisphosphate Aldolase