REGULATION OF A-L-FUCOSIDASE IN HEALTH AND DISEASE

表面健康个体血清α-L岩藻糖苷酶水平 基因决定的。该酶水平的控制机制 血清尚不清楚。作为研究这一问题的实验工具， 淋巴样细胞培养来自于遗传了 将建立血清中α-L岩藻糖苷酶活性的高低。 对于这些细胞系，将会问以下问题：1)有 多肽和多肽合成的相对速率的差异 α-L-岩藻糖苷酶的碳水化合物链 加工多肽和/或碳水化合物部分 α-L-岩藻糖苷酶？3)在分类上有差异吗？ α-L-岩藻糖苷酶进入胞内和胞外隔室？4) α-L岩藻糖苷酶活性有差异吗？回答 这些问题将为生物合成提供新的信息。 和对α-L岩藻糖苷酶的加工，将有助于 对α-L岩藻糖苷酶水平决定机制的认识 血清。这些知识除了在科学上很重要外，还可能 具有临床意义。酶活性降低的遗传性 女性血清中的α-L-岩藻糖苷与 罹患卵巢癌的风险。因此，对 控制血清中α-L岩藻糖苷酶水平的机制可能提供 关于卵巢癌的病因和遗传学的信息 与疾病易感性有关的因素。此外，更改 α-L-岩藻糖苷酶与其他严重疾病有关。这些 包括岩藻糖苷病、i-细胞病、囊性纤维化、胃癌 糖尿病、肝硬变、急性病毒性肝炎、Graves 疾病、各种肌肉疾病和急、慢性淋巴母细胞 白血病。因此，拟议的调查可能与 提高了对这些疾病的分子病理学的理解。

Levels of Alpha-L-fucosidase in serum of ostensibly healthy individuals are genetically determined. The mechanism controlling levels of the enzyme in serum is unknown. As an experimental tool to investigate this problem, lymphoid cell cultures derived from individuals who have inherited either high or low activity of Alpha-L-fucosidase in serum will be established. With these cell lines, the following questions will be asked: 1) Are there differences in the relative rates of synthesis of the polypeptide and carbohydrate chains of Alpha-L-fucosidase? 2) Are there differences in the processing the polypeptide and/or carbohydrate moieties of Alpha-L-fucosidase? 3) Are there differences in the sorting of Alpha-L-fucosidase into intracellular and extraccellular compartments? 4) Are there differences in Alpha-L-fucosidase m-RNA activity? Answers to these questions will provide novel information concerning the biosynthesis and processing of Alpha-L-fucosidase and will contribute to an understanding of the mechanism determining levels of Alpha-L-fucosidase in serum. This knowledge, besides being scientifically important, may also have clinical significance. The inheritance of decreased activity of Alpha-L-fucosidae in serum of females has been associated with increased risk for developing ovarian cancer. Thus, an understanding of the mechanism controlling levels of Alpha-L-fucosidase in serum may provide information concerning the etiology of ovarian cancer and the genetic factors involved in disease susceptibility. Moreover, alterations of Alpha-L-fucosidase have been associated with other severe diseases. These include fucosidosis, I-cell disease, cystic fibrosis, gastric cancer, diabetes mellitus, hepatic cirrhosis, acute viral hepatitis, Graves disease, various muscular diseases and acute and chronic lymphoblastic leukemia. Thus, the proposed investigations may be relevant for an improved understanding of the molecular pathology of these diseases.