Kuhlenschmidt M S, Peters S P, Pinkard O D, Glew R H, Sharp H
Biochim Biophys Acta. 1976 Apr 8;429(2):359-73. doi: 10.1016/0005-2744(76)90284-9.
The molecular basis for the accumulation of a substance which displays the immunological reactivity of alpha-1-antitrypsin within vesicles of liver parenchymal cells of individuals with hepatic cirrhosis and serum alpha-1-antitrypsin deficiency remains unclear. We recently reported that serum from a patient with alpha-1-antitrypsin deficiency and hepatic cirrhosis was substantially deficient in sialyltransferease (EC 2.4.99.1) an enzyme which transfers sialic acid from cytidine 5'-monophosphate-N-acetylneuraminic acid to a variety of asialoglycoprotein acceptors. In the present report we have extended these studies to include serum from five additional patients with alpha-1-antitrypsin deficiency and juvenile hepatic cirrhosis as well as a liver specimen obtained at autopsy of one of these patients. We find the sialytransferase activity in serum from six patients with alpha-1-antitrypsin deficiency and hepatic cirrhosis to be 50% of healthy pediatric control values and 30% of pediatric patients with liver disease. However, serum from family members homozygous for alpha-1-antitrypsin deficiency but without hepatic cirrhosis, and serum from patients with a variety of other kinds of liver disease, failed to exhibit the marked sialytransferase deficiency. Similar assays carried out on a homogenate of a liver sample from one patient with alpha-1-antitrypsin deficiency and hepatic cirrhosis indicated that the deficiency of sialyltransferase activity was not demonstrable in liver. Furthermore, a comparative kinetic analysis of serum and liver sialytransferase in normal and afflicted individuals failed to detect differences in substrate affinities which might account for a decrease in functional sialyltransferase capacity in individuals with alpha-1-antitrypsin deficiency and hepatic cirrhosis. These observations suggest that the serum sialyltransferase deficiency in such patients probably arises after chronic and extensive liver disease involving hepatic accumulation of alpha-1-antitrypsin rather than the enzyme deficiency being the primary cause of the hepatic cirrhosis and alpha-1-antitrypsin deficiency.
在患有肝硬化且血清α-1抗胰蛋白酶缺乏的个体的肝实质细胞囊泡内，一种表现出α-1抗胰蛋白酶免疫反应性的物质积累的分子基础仍不清楚。我们最近报道，一名患有α-1抗胰蛋白酶缺乏和肝硬化的患者的血清中，唾液酸转移酶（EC 2.4.99.1）严重缺乏，该酶可将胞苷5'-单磷酸-N-乙酰神经氨酸中的唾液酸转移至多种去唾液酸糖蛋白受体。在本报告中，我们将这些研究扩展至另外五名患有α-1抗胰蛋白酶缺乏和青少年肝硬化患者的血清，以及其中一名患者尸检时获得的肝脏标本。我们发现，六名患有α-1抗胰蛋白酶缺乏和肝硬化患者的血清中的唾液酸转移酶活性为健康儿童对照值的50%，为患有肝病的儿童患者的30%。然而，α-1抗胰蛋白酶缺乏但无肝硬化的纯合子家庭成员的血清，以及患有多种其他肝病患者的血清，均未表现出明显的唾液酸转移酶缺乏。对一名患有α-1抗胰蛋白酶缺乏和肝硬化患者的肝脏样本匀浆进行的类似检测表明，肝脏中未显示出唾液酸转移酶活性缺乏。此外，对正常人和患病个体的血清及肝脏唾液酸转移酶进行的比较动力学分析，未能检测到底物亲和力的差异，而这种差异可能解释了患有α-1抗胰蛋白酶缺乏和肝硬化的个体中功能性唾液酸转移酶能力的下降。这些观察结果表明，此类患者的血清唾液酸转移酶缺乏可能是在涉及α-1抗胰蛋白酶肝脏蓄积的慢性广泛性肝病之后出现的，而非酶缺乏是肝硬化和α-1抗胰蛋白酶缺乏的主要原因。
