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


CONCLUSIONS
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.
Campagnoli
Monica
M
Department of Biochemistry A Castellani, via Taramelli 3b, Università di Pavia, 27100 Pavia, Italy.
Kragh-Hansen
Ulrich
U
Overgaard Pedersen
Anders
A
Amoresano
Angela
A
Lyon
Andrew W
AW
Cesati
Roberto
R
Sala
Alberto
A
Romano
Assunta
A
Galliano
Monica
M
Minchiotti
Lorenzo
L
D001955:British Columbia; D004587:Electrophoresis, Agar Gel; D005227:Fatty Acids / Q000378:metabolism*; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D007198:Indians, North American / Q000235:genetics; D009154:Mutation; D011485:Protein Binding / Q000502:physiology; D012525:Saskatchewan; D012709:Serum Albumin / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism*; D000075462:Serum Albumin, Human; D013974:Thyroxine / Q000378:metabolism*
D005227:Fatty Acids; D012709:Serum Albumin; C096556:albumin Vancouver; D013974:Thyroxine; D000075462:Serum Albumin, Human