Jeppsson J O, Larsson C, Eriksson S
N Engl J Med. 1975 Sep 18;293(12):576-9. doi: 10.1056/NEJM197509182931203.
alpha1-antitrypsin was isolated from periodic acid-Schiff-positive inclusion bodies from the hepatocytes of patients with alpha1-antitrypsin deficiency and further purified to enable more detailed chemical analysis. Amino acid and cyanogen bromide fragmentation studies showed a close similarity between hepatic and serum (PiMM) antitrypsin in contrast to the carbohydrate analysis, which revealed markedly deficient glycosylation of hepatic antitrypsin. A complete lack of sialic acid and a relative deficiency of all other carbohydrate components could fully explain the difference of approximately 6000 daltons in molecular size between the two proteins. The accumulation of hepatic globules is probably related to the physical properties of the defective antitrypsin, which include marked insolubility and tendency toward aggregation. The results strongly suggest an abnormal amino acid sequence in the peptide chain of the deficient antitrypsin. The interference with glycosylation may be related to steric hindrance.
从α1抗胰蛋白酶缺乏症患者肝细胞的高碘酸-希夫氏阳性包涵体中分离出α1抗胰蛋白酶，并进一步纯化以进行更详细的化学分析。氨基酸和溴化氰片段化研究表明，肝脏中的抗胰蛋白酶与血清（PiMM）抗胰蛋白酶非常相似，而碳水化合物分析则显示肝脏抗胰蛋白酶的糖基化明显不足。完全缺乏唾液酸以及所有其他碳水化合物成分的相对缺乏可以充分解释这两种蛋白质在分子大小上约6000道尔顿的差异。肝脏小球的积累可能与有缺陷的抗胰蛋白酶的物理性质有关，这些性质包括明显的不溶性和聚集倾向。结果强烈表明，缺乏的抗胰蛋白酶肽链中的氨基酸序列异常。对糖基化的干扰可能与空间位阻有关。
