Structural analysis and fatty acid-binding properties of two Croatian variants of human serum albumin.
BACKGROUND
The aim of the present work was to characterize the molecular defects of a slow-migrating (albumin Zagreb) and a fast-migrating (albumin Krapina) genetic variant of human serum albumin detected in heterozygous persons living in Croatia and to elucidate the fatty acid-binding properties of the two alloalbumins.


METHODS
Purification and structural identification of the variants were performed by conventional protein chemistry methods, whereas types and amounts of albumin-bound, endogenous fatty acids were determined by gas chromatography.


RESULTS
Protein sequencing established that albumin Zagreb is a proalbumin variant (-1Arg-->Gln), and that albumin Krapina is due to a mutation within the mature polypeptide chain (573Lys-->Glu). The gas chromatographic results showed that the fatty acid-binding properties of the proalbumin variant are normal, while the amino acid substitution in position 573 resulted in a general decrease of fatty acid binding.


CONCLUSIONS
The structural defects of the first alloalbumins, detected by routine clinical electrophoresis among the Croatian population, were characterized. Albumin Zagreb is caused by a hot-spot mutation occurring in a CpG sequence in the albumin gene. It is commonly assumed that bisalbuminaemia has no direct clinical relevance. However, the present study suggests that naturally occurring mutations can affect the ligand-binding properties of human serum albumin.
Department of Medical Biochemistry, University of Aarhus, DK-8000 Aarhus C, Denmark. ukh@biokemi.au.dk
Ulrich
U
Kragh-Hansen
Monica
M
Campagnoli
Slavica
S
Dodig
Henning
H
Nielsen
Bojan
B
Benko
Miljenko
M
Raos
Roberto
R
Cesati
Alberto
A
Sala
Monica
M
Galliano
Lorenzo
L
Minchiotti
D000418:Albumins / Q000032:analysis / Q000235:genetics; D001797:Blood Protein Electrophoresis; D002648:Child; D002849:Chromatography, Gas; D017523:Croatia; D004588:Electrophoresis, Cellulose Acetate; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D014644:Genetic Variation; D006801:Humans; D007223:Infant; D007525:Isoelectric Focusing; D008024:Ligands; D008297:Male; D011485:Protein Binding; D012709:Serum Albumin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D000418:Albumins; D005230:Fatty Acids, Nonesterified; D008024:Ligands; D012709:Serum Albumin; C030764:bisalbumins