INBORN ERRORS OF CARBOHYDRATE METABOLISM

具体目标和长期目标。我们的研究旨在全面了解 对肝脏和其他动物体内碳水化合物代谢的了解 纸巾：以一种平行和互补的方式，我们倾向于给一个 相关先天性疾病的生化解释 最终得到了适当的治疗。在接下来的几年里，我们 研究将更具体地定位于阐明 葡萄糖激酶的调控，进一步研究其作用 生物中的2，6-二磷酸果糖与糖原的各个方面 新陈代谢。我们还将尝试检测新陈代谢的先天缺陷 与这些特定主题中的每一个相关。此外，我们还将继续 深入调查新发现的营养不良问题 甘油酸激酶。溶酶体和过氧化物体的疾病也将 在对这些细胞器进行基础研究的同时，进行了研究。 方法学，肝脏和肌肉活检来自不同影响的患者 先天代谢性疾病(主要是糖原堆积症、果糖 不耐受、先天性乳酸血症、半乳糖血症、先天性溶酶体 疾病)在本实验室经常收到来自许多临床 中心主要位于西欧，但也位于南美和 其他国家。这些活组织检查将提交给生化和 超微结构研究。葡糖激活剂及其应用的基础研究 糖原代谢将与提取物和纯化的蛋白质从 大鼠肝脏、肌肉、胰岛和酵母。未知的角色 生物中的2，6-二磷酸果糖将被 调查。葡萄糖激酶与糖原代谢的基础研究 将由大鼠肝脏、肌肉、 胰岛和酵母。果糖2，6-的未知作用 生物中的二磷酸盐将通过研究 酵母突变株的行为，其中编码酶的基因 形成或降解果糖2，6-二磷酸会被删除 或者过度表达。过氧化体在脂肪酸氧化中的作用将是 大鼠肝脏和肝脏中部分纯化的过氧化物体部分的研究 形成的肉碱衍生物将通过串联质谱仪进行分析 光谱分析。

Specific aims and long-term objectives. Our research is aimed at a full understanding of carbohydrate metabolism in the liver and other animal tissues: in a parallel and complementary way, we tend to give a biochemical explanation to the related congenital disorders allowing eventually an appropriate treatment. During the next few years, our research will be more specifically oriented towards the elucidation of the control of glucokinase, a further investigation of the role of fructose 2,6-bisphosphate in biology and various aspects of glycogen metabolism. We will also try to detect inborn errors of metabolism related to each of these specific subjects. Furthermore, we will pursue an intensive investigation of the newly discovered deficiency of glycerate kinase. Disease of lysosomes and peroxisomes will also be studied, in parallel with basic research on these organelles. Methodology, Liver and muscle biopsies from patients affected by various inborn errors of metabolism (mostly glycogen storage disease, fructose intolerance, congenital lacticacidemia, galactosemia, inborn lysosomal disease) are regularly received in this laboratory from many clinical centers located mostly in Western Europe but also in South American and other countries. These biopsies will be submitted to both biochemical and ultrastructural investigations. Basic research on glucokinase and glycogen metabolism will be made with extracts and purified proteins from rat liver, muscle, pancreatic islets and yeast. The unknown roles of fructose 2,6-bisphosphate in biology will be searched for by investigations. Basic research on glucokinase and glycogen metabolism will be made with extracts and purified proteins from rat liver, muscle, pancreatic islets, and yeast. The unknown roles of fructose 2,6- bisphosphate in biology will be searched for by investigating the behaviour of yeast mutants in which the genes encoding the enzymes that form or degrade fructose 2,6-bisphosphate would have been either deleted or overexpressed. The role of peroxisomes in fatty acid oxidation will be studied in partially purified peroxisomal fractions from rat liver and the carnitine derivatives formed will be analyzed by tandem mass spectrometry.