INBORN ERRORS OF CARBOHYDRATE METABOLISM

具体目标和长期目标。我们的研究旨在全面 了解肝脏和其他动物的碳水化合物代谢 组织：在一个平行和互补的方式，我们倾向于给一个 相关先天性疾病的生化解释， 最终得到适当的治疗。在接下来的几年里，我们 研究将更具体地面向阐明 葡萄糖激酶的控制，进一步研究 果糖2，6-二磷酸在生物学和糖原的各个方面 新陈代谢.我们还将尝试检测先天性代谢缺陷 与这些具体问题有关。此外，我们将继续 对新发现的 甘油酸激酶溶酶体和过氧化物酶体的疾病也将是 研究，与这些细胞器的基础研究平行。 方法学，肝脏和肌肉活组织检查，来自受各种 先天性代谢缺陷（主要是糖原累积病，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）定期收到在这个实验室从许多临床 中心主要位于西欧，但也在南美和 其他国家这些活组织检查将提交给生化和 超微结构研究葡萄糖激酶的基础研究及 糖原代谢将与提取物和纯化的蛋白质， 大鼠肝脏、肌肉、胰岛和酵母。未知的角色 生物学中的果糖2，6-二磷酸将被搜索， 调查事务所葡萄糖激酶与糖原代谢的基础研究 将用从大鼠肝脏，肌肉， 胰岛和酵母。果糖2，6- 生物学中的二磷酸盐将通过调查 酵母突变体的行为，其中基因编码的酶， 形成或降解2，6-二磷酸果糖的基因 或过度表达。过氧化物酶体在脂肪酸氧化中的作用 在大鼠肝脏的部分纯化过氧化物酶体组分中进行了研究， 形成的肉毒碱衍生物将通过串联质谱分析， 光谱法

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.