INBORN ERRORS OF CARBOHYDRATE METABOLISM

具体目标和长期目标。我们的研究目标是全面

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.