INBORN ERRORS OF CARBOHYDRATE METABOLISM

我们的研究旨在全面了解 肝脏和其他动物组织;以平行和互补的方式， 倾向于对相关的先天性疾病给予生物化学解释 最终得到适当的治疗。 在接下来的几年里， 我们的研究将更具体地面向调查 果糖2，6-二磷酸在各种代谢控制中的作用 并涉及与颗粒结合的蛋白质的表征 糖原在肝脏;我们也将尝试检测先天性的错误， 与果糖的形成或降解有关的代谢 2，6-二磷酸。 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。 来自受各种先天性缺陷影响的患者的肝脏和肌肉活检 代谢（主要是糖原累积病，果糖不耐症， 先天性乳酸性酸中毒、半乳糖血症、先天性溶酶体疾病）， 本实验室定期收到来自位于 大多数在西欧，但也在南美和其他国家。 这些活检将提交给生化和超微结构 调查 2，6-二磷酸果糖的实验工作将在 通过对这种化合物的灵敏测定， 涉及（1）磷酸果糖的纯化和比较研究 2-激酶和果糖2，6-二磷酸酶，也使 使用针对这些蛋白质的单克隆抗体;（2） 寻找使用果糖2，6-二磷酸作为底物或作为 （3）参与的蛋白磷酸酶的表征 磷酸果糖2-激酶的去磷酸化。 为研究 糖原结合酶，颗粒糖原将被分离的新的 非常快速的程序。

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 to an investigation of the role of fructose 2,6-bisphosphate in the control of metabolism in various tissues and to a characterization of the proteins bound to particulate glycogen in the liver; we will also try to detect inborn errors of metabolism related to the formation or degradation of fructose 2,6-bisphosphate. Diseases of lysosomes and peroxisomes will also be studied, in parallel with basic research on these organelles. Liver and muscle biopsies from patients affected by various inborn errors of metabolism (mostly glycogen storage disease, fructose intolerance, congenital lactic acidosis, galactosemia, inborn lysosomal diseases) are regularly received in this laboratory from many clinical centers located mostly in western Europe but also in South America and other countries. These biopsies will be submitted to both biochemical and ultrastructural investigation. Experimental work on fructose 2,6-bisphosphate will be facilitated by an exquisitely sensitive assay for this compound and will involve (1) the purification and a comparative study of phosphofructo 2-kinase and fructose 2,6-bisphosphatase from various origin, also making use of monoclonal antibodies directed against these proteins; (2) the search for new enzymes using fructose 2,6-bisphosphate as a substrate or as a cofactor; (3) a characterization of the protein phosphatases involved in the dephosphorylation of phosphofructo 2-kinase. For the study of glycogen-bound enzymes, particulate glycogen will be isolated by a new extremely rapid procedure.