PATHOGENESIS OF AMP DEAMINASE DEFICIENCY

AMP脱氨酶及其所属的嘌呤核苷酸环 对于组织中的能量新陈代谢来说是非常重要的。这个 这一循环在能量代谢中的作用已在 骨骼肌，这些酶的活性是 特别是高的，组织特异性的亚型被发现，和通量 随着运动的进行，整个周期会急剧增加。这个 这一周期在骨骼肌中的临床相关性被强调。 遗传性肌病患者发生的肌病 核苷酸循环酶的缺陷。AMP脱氨酶 缺陷，这个周期中最常见的缺陷，与 患有运动相关的肌病。 这些研究的目的是为了了解AMP的调节 脱氨酶在正常和病理条件下的表达。安培 脱氨酶以多种形式存在，其中一些是组织- 具体的。有一组项目设计为使用特定于等同格式的 抗血清和核酸探针用于研究发育和 动物模型中异构体表达的组织特异性调控 心肌细胞分化的组织培养模型。另一套 实验旨在评估不同领域的功能 利用体内和体外表达的AMP脱氨酶 载体，目标是将特定于异构体的属性本地化到 不同的域。第三组项目旨在 确定遗传性和获得性的分子基础 用药患者AMP脱氨酶缺陷的研究 异构体特异性和核酸探针。 这些研究的结果与理解 正常人AMP脱氨酶和嘌呤核苷酸循环的控制 AMP脱氨酶的条件及发病机制的认识 缺乏症。研究结果可能具有更广泛的意义，因为它提供了 对控制心肌细胞的过程的更多了解 差异化。

AMP deaminase and the purine nucleotide cycle of which it is one component are important for energy metabolism in may tissues. The role of this cycle in energy metabolism has been best studied in skeletal muscle where the activities of these enzymes are particularly high, tissue-specific isoforms are found, and flux through the cycle increases dramatically with exercise. The clinical relevance of this cycle in skeletal muscle is highlighted by the myopathy which develops in patients with inherited deficiencies of nucleotide cycle enzymes. AMP deaminase deficiency, the most common defect in this cycle, is associated with an exercise-related myopathy. The purpose of these studies is to understand the regulation of AMP deaminase expression in normal and pathological conditions. AMP deaminase exists in multiple isoforms, some of which are tissue- specific. One set of projects is designed to use isoform specific anti-sera and nucleic acid probes to study developmental and tissue-specific control of isoform expression in animal models and a tissue culture model of myocyte differentiation. Another set of experiments is designed to assess the function of different domains of AMP deaminase through the use of in vivo and in vitro expression vectors with the goal of localizing isoform-specific properties to different domains. A third set of projects is designed to determine the molecular bases of inherited and acquired deficiencies of AMP deaminase through the study of patients using isoform-specific and nucleic acid probes. Results of these studies have direct relevance to understanding the control of AMP deaminase and the purine nucleotide cycle in normal conditions and to understanding the pathogenesis of AMP deaminase deficiency. The results may have broader significance by providing additional insight to processes which control myocyte differentiation.