INBORN ERRORS OF CARBOHYDRATE METABOLISM

碳水化合物代谢的先天性错误

• 批准号: 3224602
• 负责人: HENRI-GERY HERS
• 金额: $ 6.06万
• 依托单位: CATHOLIC UNIVERSITY OF LOUVAIN
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-06-01 至 1992-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3224602
• 关键词: acidosis; acyltransferase; biopsy; carnitine; electron microscopy; fibroblasts; fructose biphosphatase; fructose phosphate; glucokinase; gluconeogenesis; glycogen; glycogen storage disease type I; glycogen storage disease type VII; glycolysis; hereditary fructose intolerance; human subject; human tissue; inborn carbohydrate metabolism disorder; inborn lysosomal enzyme disorder; inborn metabolism disorder; inborn metabolism disorder diagnosis; laboratory rat; liver cells; liver metabolism; mass screening; orphan disease /drug; peroxisome; tissue /cell culture

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.

具体目标和长期目标。我们的研究目标是全面