Gluconeogenesis Glucose-6-phosphatase

Gluconeogenesis 1 TORC2, others l Expression PEP carboxykinase, glucose-6-phosphatase Liver... 

Metformin restrains hepatic glucose production principally by suppression of gluconeogenesis. The mechanisms involve potentiation of insulin action and decreased hepatic extraction of certain gluconeogenic substrates such as lactate. In addition, metformin reduces the rate of hepatic glycogenolysis and decreases the activity of hepatic glucose-6-phosphatase. Insulin-stimulated glucose uptake and glycogenesis by skeletal muscle is increased by metformin mainly by increased... 

The free glucose produced by this reaction is supplied to the blood from the tissues. As exemplified by gluconeogenesis, one may easily envision the economical organization of these metabolic routes, since, apart from four special gluconeogenesis enzymes-pyruvate carboxylase, phosphopyruvate carboxylase, fructose bisphosphatase, and glucose 6-phosphatase-individual glycolytic enzymes are also used in the gluconeogenesis. 

Two gluconeogenesis-specific phosphatases then successively cleave off the phosphate residues from fructose 1,6-bisphos-phate. In between these reactions lies the isomerization of fructose 6-phosphate to glucose 6-phosphate—another glycolytic reaction. 

The glucocorticoids have important dose-related effects on carbohydrate, protein, and fat metabolism. The same effects are responsible for some of the serious adverse effects associated with their use in therapeutic doses. Glucocorticoids stimulate and are required for gluconeogenesis and glycogen synthesis in the fasting state. They stimulate phosphoenolpyruvate carboxykinase, glucose-6-phosphatase, and glycogen synthase and the release of amino acids in the course of muscle catabolism. 

Diabetes - insulin dependent Methyl malonic, propionic or isovaleric acidaemias Pyruvate carboxylase and multiple carboxylase deficiency Gluconeogenesis enzyme deficiency glucose-6-phosphatase, fructose-1,6-diphosphatase or abnormality of glycogen synthesis (glycogen synthase) Ketolysis defects Succinyl coenzyme A 3-keto acid transferase ACAC coenzyme A thiolase... 

Gluconeogenesis uses seven of the reactions in glycolysis, but three are replaced by the sum of the pyruvate carboxylase and phosphoeno/pyruvate carboxykinase reactions, the fructose 1,6-biphosphatase reaction, and the glucose 6-phosphatase reaction. Tables 4.7, 4.8, and 4.9 give the thermodynamic properties of these reactions and the net reaction for gluconeogenesis. 

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