1. Structural analysis and fatty acid-binding properties of two Croatian variants of human serum albumin
- Author
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Henning Nielsen, Monica Galliano, Slavica Dodig, Miljenko Raos, Lorenzo Minchiotti, Ulrich Kragh-Hansen, Alberto Sala, Roberto Cesati, Bojan Benko, and Monica Campagnoli
- Subjects
Male ,Chromatography, Gas ,Croatia ,Clinical Biochemistry ,Population ,Serum albumin ,Plasma protein binding ,Fatty Acids, Nonesterified ,Ligands ,Biochemistry ,Albumins ,Fatty acid binding ,medicine ,Humans ,Child ,education ,Serum Albumin ,education.field_of_study ,albumin Zagreb ,albumin Krapina ,albuminska varijanta ,proalbuminska varijanta ,točkasta mutacija ,bisalbuminemija ,vezanje masnih kiselina ,plinska kromatografija ,biology ,Point mutation ,Biochemistry (medical) ,Albumin ,Genetic Variation ,Infant ,Electrophoresis, Cellulose Acetate ,General Medicine ,Blood Protein Electrophoresis ,Human serum albumin ,medicine.disease ,biology.protein ,Isoelectric Focusing ,Bisalbuminemia ,Protein Binding ,medicine.drug - Abstract
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.
- Published
- 2004