Observations on double albumin. II. A peptide difference between two genetically determined human serum albumins.

An unusual serum protein anomaly, the occurrence of two electrophoretically distinct albumins in the same serum, was recently reported by Knedel (2, 3) who observed the abnormality in eight members of two different families and termed the condition "double-albuminemia." A similar anomaly was found by Earle, Hutt, Schmid and Gitlin in 25 of 43 individuals in a single family (4, 5), and additional families with double-albuminemia have been reported by others (6-10). In all of these studies it was clear that the albumin anomaly was transmitted genetically as an autosomal characteristic, the appearance of two serum albumins in the same individual being a manifestation of the heterozygous state. In the studies reported by Earle and co-workers, the two albumins proved to be immunochemically and ultracentrifugally indistinguishable from each other and from normal human serum albumin. Differential electrophoretic titration revealed that between pH 4.5 and 10, albumin A had a greater net negative charge than had albumin B, but at pH 3.5 and between pH 11.6 and 12.3 both albumins appeared to have the same electrophoretic mobility. The simplest explanation of the data suggested a substitution of either tyrosine, cysteine or lysine in albumin B for a carboxyl residue in albumin A. Albumin A in all respects appeared to be normal human serum albumin, while albumin B was definitely anomalous. In the study reported here, albumins A and B were hydrolyzed enzymatically and the resultant