alpha-1-Antitrypsin metabolism in the protein-deficient weanling rat.
Protein-deficient weanling rats fed on a 30 g casein/kg diet for 3 weeks lost albumin but maintained the level of serum alpha-1-antitrypsin, the most abundant protease inhibitor in blood. alpha-1-Antitrypsins from malnourished rats and control rats (given 250 g casein/kg diet) differed; the protease inhibitor from protein-deficient animals: (1) was more acidic, (2) appeared slightly larger (57 400 v. 56 000 daltons) on sodium dodecyl sulphate (SDS)-polyacrylamide gels, (3) had a more acidic Pi type and increased anodal mobility at pH 8.9, (4) bound more concanavalin-A and contained more carbohydrate, specifically two to three extra sialic acid residues. The amino sugar and neutral sugar contents of both preparations of alpha-1-antitrypsin were the same. Analysis of the products of cyanogen-bromide cleavage revealed that alpha-1-antitrypsin preparations from protein-deficient rats contain an extra glycopeptide that was not present in alpha-1-antitrypsin from control animals. In vivo studies showed that the increased sialic acid content of alpha-1-antitrypsin of protein-deficient rats did not alter the half-life of the molecule in the blood of control rats. However, the fractional catabolic rate of alpha-1-antitrypsin from either well-nourished or protein-deficient rats was significantly (P less than 0.01) lower in protein-deficient rats than in control rats (0.0247/h v. 0.0406/h). The decreased fractional catabolic rate could not be explained by changes in hepatic mannosyl-, galactosyl- or N-acetylhexosaminyl receptors since liver perfusion studies showed that bovine serum albumin, when covalently modified separately with each of these ligands, was extracted from the perfusion medium as rapidly or more rapidly by livers from malnourished animals. Perfused livers from protein-deficient rats secrete three times more alpha-1-antitrypsin than do livers from well-nourished animals. The decreased fractional catabolic rate and increased rate of biosynthesis and secretion of the glycoprotein by livers from protein-deficient animals may account for the maintenance of alpha-1-antitrypsin levels during protein malnutrition.
D000418:Albumins / Q000378:metabolism; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D001212:Asialoglycoproteins; D001835:Body Weight; D002241:Carbohydrates / Q000032:analysis; D003208:Concanavalin A / Q000378:metabolism; D003488:Cyanogen Bromide; D004586:Electrophoresis; D006023:Glycoproteins / Q000378:metabolism; D007457:Iodine Radioisotopes; D008099:Liver / Q000378:metabolism; D009961:Orosomucoid / Q000031:analogs & derivatives / Q000378:metabolism; D011488:Protein Deficiency / Q000378:metabolism*; D051381:Rats; D012709:Serum Albumin / Q000032:analysis; D014886:Weaning; D000515:alpha 1-Antitrypsin / Q000097:blood / Q000302:isolation & purification / Q000378:metabolism*
D000418:Albumins; D000596:Amino Acids; D001212:Asialoglycoproteins; D002241:Carbohydrates; D006023:Glycoproteins; D007457:Iodine Radioisotopes; D009961:Orosomucoid; D012709:Serum Albumin; D000515:alpha 1-Antitrypsin; C017030:asialoorosomucoid; D003208:Concanavalin A; D003488:Cyanogen Bromide