Effect of genetic variation on the fatty acid-binding properties of human serum albumin and proalbumin.
In the circulation, non-esterified fatty acids are transported by albumin which also facilitates their removal from donor cells and uptake into receptor cells. We have studied whether genetic variations in the albumin molecule can affect its in vivo fatty acid-binding properties. The fatty acids bound to 25 structurally different variants and to their wildtype counterparts, isolated from heterozygous carriers, were determined gas chromatographically. The variants were proalbumins, albumins with single amino acid substitutions and glycosylated or truncated albumins. In eight cases the total amount bound to the variants was diminished (0.4-0.8-fold), and in seven cases the load was increased to 1.3 or more of normal. Twenty-one fatty acids were quantitated, and for 19 alloalbumins significant deviations from normal were found. Usually, changes in total and individual fatty acid binding were of the same type, but several exceptions to this rule was found. The glycosylated albumin Casebrook showed the largest changes, the total load and the amount of bound palmitate was 8.6 and 14 times, respectively, the normal. The most pronounced changes and the majority of cases of increased binding were caused by molecular changes in domain III. Mutations in domain I, II and the propeptide resulted in smaller effects, if any, and these were often reductions in binding.
Nielsen
H
H
Department of Medical Biochemistry, University of Aarhus, Denmark.
Kragh-Hansen
U
U
Minchiotti
L
L
Galliano
M
M
Brennan
S O
SO
Tárnoky
A L
AL
Franco
M H
MH
Salzano
F M
FM
Sugita
O
O
D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000097:blood* / Q000737:chemistry / Q000235:genetics*; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids / Q000032:analysis / Q000097:blood*; D006580:Genetic Carrier Screening; D014644:Genetic Variation; D006801:Humans; D008969:Molecular Sequence Data; D018996:Myelin P2 Protein / Q000097:blood* / Q000737:chemistry / Q000235:genetics*; D009363:Neoplasm Proteins; D011228:Prealbumin / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012709:Serum Albumin / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D025521:Tumor Suppressor Proteins
D002352:Carrier Proteins; C107608:FABP7 protein, human; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D018996:Myelin P2 Protein; D009363:Neoplasm Proteins; D011228:Prealbumin; D012709:Serum Albumin; D025521:Tumor Suppressor Proteins