Structural analysis, fatty acid and thyroxine binding properties of Vancouver and Naskapi variants of human serum albumin.

OBJECTIVES

To purify and structurally identify two albumin variants found in the Canadian population of native Amerindian origin. To assess the ability of variant albumins to bind lauric acid and L-thyroxine.

METHODS

The structural characterization of the alloalbumins was performed by conventional protein chemistry methods and by mass spectrometric analysis. Lauric acid and L-thyroxine affinities to variant albumins were assessed by kinetic dialysis and equilibrium dialysis techniques, respectively.

RESULTS

The sequence investigations proved the two variants to be albumin Naskapi [372Lys --> Glu] and albumin Vancouver [501Glu --> Lys], respectively. Among the carriers of albumin Naskapi, we found a rare case of homozygosity. Furthermore, this is the first reported case of the 501Glu-->Lys mutation in the native North American population. Scatchard plot analysis revealed that the association constants for lauric acid and L-thyroxine to the two variants were indistinguishable from the endogenous form of albumin.

CONCLUSION

We show that albumin variants Vancouver and Naskapi have normal fatty acid and L-thyroxine binding capabilities. These findings support the assumption that bisalbuminemias associated with these albumin variants are benign conditions.