The molecular defects of three different slow-migrating genetic variants of
human serum albumin, albumins Kamloops (formerly RM), Stirling and Amsterd
am, previously characterized only by electrophoretic and dye-binding studie
s, are now reported. Two of them are proalbumin variants: sequential analys
is of the purified whole proteins has established the mutation responsible
for albumin Kamloops as -1Arg --> Gln, and for albumin Stirling as - 2Arg -
-> His. A Glu --> Lys substitution in position 570 of the mature albumin mo
lecule was determined in albumin Amsterdam by sequential analysis of two ab
normal tryptic fragments. The three alloalbumins are caused by single-base
changes all of which seem to represent hot-spots in the albumin gene. The p
ossible functional consequences of the presence of a circulating alloalbumi
n are discussed. (C) 1999 Elsevier Science B.V. All rights reserved.