INBORN ERRORS OF CARBOHYDRATE METABOLISM

我们的研究旨在全面了解人体的碳水化合物代谢

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.