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 albu min which also facilitates their removal from donor cells and uptake i nto 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 th eir wildtype counterparts, isolated from heterozygous carriers, were d etermined gas chromatographically. The variants were proalbumins, albu mins with single amino acid substitutions and glycosylated or truncate d 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 t o 1.3 or more of normal. Twenty-one fatty acids were quantitated, and for 19 alloalbumins significant deviations from normal were found. Usu ally, changes in total and individual fatty acid binding were of the s ame type, but several exceptions to this rule was found. The glycosyla ted albumin Casebrook showed the largest changes, the total load and t he amount of bound palmitate was 8.6 and 14 times, respectively, the n ormal, The most pronounced changes and the majority of cases of increa sed 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. (C) 1997 Elsevier Scienc e B.V.