Lewis E C, Glew R H, Chambers J, Coyle P, Coppes J
Br J Nutr. 1985 Jul;54(1):63-77. doi: 10.1079/bjn19850093.
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.
以每千克含30克酪蛋白的饲料喂养3周的蛋白质缺乏断乳大鼠，白蛋白减少，但血清α-1-抗胰蛋白酶水平维持不变，α-1-抗胰蛋白酶是血液中最丰富的蛋白酶抑制剂。营养不良大鼠和对照大鼠（给予每千克含250克酪蛋白的饲料）的α-1-抗胰蛋白酶不同；蛋白质缺乏动物的蛋白酶抑制剂：（1）酸性更强，（2）在十二烷基硫酸钠（SDS）-聚丙烯酰胺凝胶上显得稍大（57400对56000道尔顿），（3）具有更酸性的Pi类型，在pH 8.9时阳极迁移率增加，（4）结合更多伴刀豆球蛋白A且含有更多碳水化合物，特别是多两到三个唾液酸残基。两种α-1-抗胰蛋白酶制剂的氨基糖和中性糖含量相同。对溴化氰裂解产物的分析表明，蛋白质缺乏大鼠的α-1-抗胰蛋白酶制剂含有一种对照动物的α-1-抗胰蛋白酶中不存在的额外糖肽。体内研究表明，蛋白质缺乏大鼠的α-1-抗胰蛋白酶增加的唾液酸含量并未改变该分子在对照大鼠血液中的半衰期。然而，蛋白质缺乏大鼠中，来自营养良好或蛋白质缺乏大鼠的α-1-抗胰蛋白酶的分解代谢率分数显著（P小于0.01）低于对照大鼠（分别为0.0247/小时对0.0406/小时）。分解代谢率分数降低无法用肝脏甘露糖基、半乳糖基或N-乙酰己糖胺基受体的变化来解释，因为肝脏灌注研究表明，当牛血清白蛋白分别与这些配体之一进行共价修饰时，营养不良动物的肝脏从灌注介质中提取牛血清白蛋白的速度与对照动物的肝脏一样快或更快。蛋白质缺乏大鼠的灌注肝脏分泌的α-1-抗胰蛋白酶比营养良好动物的肝脏多两倍。蛋白质缺乏动物肝脏中糖蛋白的分解代谢率分数降低以及生物合成和分泌速率增加，可能解释了蛋白质营养不良期间α-1-抗胰蛋白酶水平的维持。
