INBORN ERRORS OF CARBOHYDRATE METABOLISM

我们的研究旨在全面了解碳水化合物代谢 肝脏和其他动物组织；我们以并行和互补的方式 倾向于对相关先天性疾病给出生化解释 最终允许适当的治疗。 在接下来的几年里， 我们的研究将更具体地针对以下方面的调查： 果糖2,6-二磷酸在控制各种代谢中的作用 组织和与颗粒结合的蛋白质的表征 肝脏中的糖原；我们还将尝试检测先天性错误 与果糖的形成或降解相关的代谢 2,6-二磷酸。 溶酶体和过氧化物酶体疾病也会 与这些细胞器的基础研究同时进行。 受各种先天性缺陷影响的患者的肝脏和肌肉活检 代谢障碍（主要是糖原贮积病、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） 该实验室定期收到来自许多临床中心的信息 主要在西欧，但也有南美和其他国家。 这些活检将提交给生化和超微结构 调查。 果糖2,6-二磷酸的实验工作将是 通过对该化合物进行极其灵敏的测定来促进，并且将 涉及（1）磷酸果糖的纯化及比较研究 来自不同来源的 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） 使用果糖 2,6-二磷酸作为底物或作为寻找新的酶 辅助因子； (3) 蛋白质磷酸酶的表征 磷酸果糖2-激酶的去磷酸化。 为了研究 糖原结合酶、颗粒糖原将通过新的方法分离 极其快速的过程。

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.