Intracellular distribution of serum albumin and its possible precursors in rat liver

Abstract

1. The fractionation of intracellular albumin labelled with radioactive l-leucine was studied in rat liver by means of isoelectric focusing. 2. Isoelectric fractionation was compared with ion-exchange chromatography for purification of radioactive intracellular albumin obtained by antibody precipitation. Similar results were obtained with both methods of separation. Purified albumin contains only a minor amount of the radioactivity. The remainder is associated with albumin-like protein(s). 3. The albumin-like protein has the properties of a precursor of plasma albumin. 4. The distribution and turnover of radioactive albumin in rough and smooth microsomal fractions and in a Golgi-rich fraction were studied. 5. It is concluded that newly synthesized albumin, as such, appears only momentarily if at all in any intracellular structure before its appearance in the plasma. 6. It is also concluded that the rate-limiting step in the secretion of plasma albumin is the conversion of precursor(s) into albumin. We can find no evidence to suggest that there is any significant transport of albumin, as such, during the course of secretion.

Pathogenesis of alcohol-induced accumulation of protein in the liver.

“…The material present in the immunc tates has properties compatible with those bumin precursor-proalbumin (31,42,43 [44], and alcohol dehydrogenase [45]) is unchanged or decreased in ethanol-fed rats.…”

The Kinetics in vivo of the Synthesis of Albumin‐Like Protein and Albumin in Rats

“…This is due to the presence in these tissues of a protein similar to albumin [6,7,9,10]. When applying appropriate purification procedures, Judah and Nicholls observed that liver slices continued to incorporate ['4C]leucine into albumin after incorporation into total protein had been interrupted by cycloheximide or excess unlabelled leucine [Ill.…”

“…In contrast to the easy isolation from serum, rather extensive purification is required to obtain pure albumin from biological material involved in albumin synthesis, such as liver [l-41, hepatoma [2,3], hepatocyte suspensions [ 5 ] , and cell-free proteinsynthesizing systems from liver [6-81. This is due to the presence in these tissues of a protein similar to albumin [6,7,9,10]. When applying appropriate purification procedures, Judah and Nicholls observed that liver slices continued to incorporate ['4C]leucine into albumin after incorporation into total protein had been interrupted by cycloheximide or excess unlabelled leucine [Ill.…”

The synthesis and secretion of albumin

“…The term antialbumin-precipitable protein has been introduced to refer to the sum of albumin and its precursor proteins (Edwards et al, 1976a,b,c;Urban et al, 1976). Albumin can be separated from albumin-like proteins (precursors) by ion-exchange chromatography on DEAE-cellulose or on CM-cellulose Rotermund et al, 1970;Judah and Nicholls, 1971a;Geller et al, 1972;Judah et al, 1973;Urban et al, 1974a,b), electrophoresis in polyacrylamide gel Rotermund et al, 1970;Urban et al, 1974b), or cellulose acetate (Peters, 1977) and isoelectric focusing (Geller et al, 1972;Russell and Geller, 1975). An example for the separation of albumin and precursor albumin by chromatography on DEAE-cellulose is shown in Figures 3 and 4.…”