OXIDATIVE METABOLISM IN INHERITED NEUROLOGICAL DISEASES AND MYCOPLASMAS

遗传性神经疾病和支原体中的氧化代谢

• 批准号: 3969019
• 负责人: G CONSTANTOPOULOS
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3969019
• 关键词: Friedreich's ataxia; Mycoplasma; bacterial disease; communicable disease diagnosis; electron microscopy; fibroblasts; genetic disorder; glutamate dehydrogenase; human tissue; inborn metabolism disorder; malate dehydrogenase; mitochondria; nervous system disorder; nervous system disorder diagnosis; oxidation; pyruvate dehydrogenase

An increasing amount of evidence points to a possible defect in oxidative metabolism in patients with certain inherited neurological disorders. Thus, a defect in the pyruvate oxidation system has been shown in some patients with lactic acidemia and diffuse neurologic disease, of the mitochondrial malic enzyme in patients with Friedreich's ataxia, and a partial deficiency of glutamate dehydrogenase in some patients with olivopontocerebellar degeneration. However, there is much controversy about the exact enzymatic defect(s). The objective of this project is the elucidation of the defect in some of these patients or in skin fibroblasts derived from such patients. For this purpose we are assaying a number of mitochondrial and non-mitochondrial enzymes in fibroblasts or leukocytes and we have initiated electron microscopic studies of the mitochondria. We became interested in the oxidative metabolism of mycoplasmas because mycoplasma contamination of fibroblast cultures interfered with the assay of pyruvate dehydrogenase complex in these cells. The oxidative metabolism of mycoplasmas is poorly understood. Hopefully, the elucidation of the defect in these diseases will help in the diagnosis and therapeutic intervention in the patients. Knowledge of the physiology of mycoplasmas may help in understanding the pathogenicity of these organisms.

越来越多的证据表明， 某些遗传性神经系统疾病患者的代谢。 因此，在一些实施方案中已经显示丙酮酸氧化系统的缺陷。 患有乳酸血症和弥漫性神经系统疾病的患者， Friedreich共济失调患者的线粒体苹果酸酶， 部分患者谷氨酸脱氢酶缺乏， 橄榄体脑桥小脑变性 然而， 关于确切的酶缺陷。 该项目的目标是 阐明这些患者或皮肤成纤维细胞中的缺陷 从这样的病人身上。 为此，我们正在分析一些 成纤维细胞或白细胞中的线粒体和非线粒体酶 我们已经开始了线粒体的电子显微镜研究。 我们 对支原体的氧化代谢产生了兴趣， 成纤维细胞培养物的支原体污染干扰测定 丙酮酸脱氢酶复合物的合成 氧化代谢 对支原体的了解很少。 希望，对这一问题的解释 这些疾病的缺陷将有助于诊断和治疗 对患者的干预。 支原体生理学知识 可能有助于了解这些生物的致病性。