Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.1.1 (hexokinase)
 5,274 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glucose can modulate the transcription of many genes, particularly those encoding enzymes of liver metabolism. The transcriptional effect of glucose can be indirect, being mediated in vivo by hormonal variations, especially increase in insulin and decrease in glucagon secretion. Whereas the transcription of the glucokinase gene, for example, is stimulated by insulin without the aid of glucose, the transcriptional activation of most glycolytic and lipogenic genes in hepatocytes requires the presence of both glucose and insulin. The role of insulin in the activation of these genes seems mainly to stimulate glucokinase synthesis, and thus to permit glucose phosphorylation. In some cells in which hexokinase activity is constitutive, the glucose-dependent activation of the same genes does not require insulin and, in addition, can be produced by the nonmetabolisable analog, 2-deoxyglucose. In hepatocytes, the insulin effect on the glucose-dependent activation of the L-pyruvate kinase gene can be reproduced by fructose at low concentrations. Fructose probably acts through the fructose 1-phosphate dependent deinhibition of glucokinase activity. A glucose/carbohydrate element has been identified on the L-type pyruvate kinase and spot 14 gene promoters. It is able to bind, in vitro, transcriptional factors of the MLTF/USF family and could act in cooperation with tissue-specific contiguous elements, such as the HNF4 binding site in the L-type pyruvate kinase gene.
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PMID:Transcriptional control of metabolic regulation genes by carbohydrates. 829 88

Glucose, that Claude Bernard has demonstrated in 1850 to be synthesized and secreted by the liver, is an important regulator of gene transcription in all types of organisms. In vertebrates, it especially regulates transcription of metabolic genes in the liver and fat tissue, activating genes encoding enzymes and regulators of the glycolytic and lipogenic pathways. Working with the L-type pyruvate kinase gene we have found that in hepatocytes glucose-dependent gene regulation requires: Presence of the GLUT2 glucose transporter, necessary to allow for an effective depletion in glucose 6-phosphate (G-6P) under gluconeogenic conditions. Phosphorylation of glucose to G-6P assured either by insulin-dependent glucokinase or by another hexokinase isoform. Most likely, entry of G-6P in the pentose phosphate pathway. Modulation of a kinase/phosphatase cascade, in particular inhibition of the 5'AMP-activated protein kinase. Signalling through a glucose response complex assembled onto a glucose-response element (GIRE) located in regulatory regions of glucose-responsive genes. The activators USF belong to the complex, and are required for a normal gene activation by glucose, as evidenced from the phenotype of knock-out mice deficient in USF. The study of USF-defective knock-out mice suggest that USF could be involved in nutritional activation of a whole class of genes regulated by glucose, and not by insulin itself. In particular, lipogenic genes and the ob gene, encoding the leptin satiety hormone, are abnormally responsive to diet in USF-/- mice. The transactivation potential of USF would be modulated by a glucose sensor system implying the COUP-TFII transcription inhibitor. The main role of insulin in the glucose response of genes like the L-PK gene is to induce the glucokinase gene. Glucagon, through cyclic AMP, inhibits L-PK gene transcription mainly through activation of PKA. The PKA catalytic subunit could act by phosphorylating member(s) of the glucose-response complex, or of contiguous transcription factor, e.g. HNF4. In conclusion, through a pluridisciplinary approach ranging from Claude Bernard-derived biology to modern molecular biology, important progress have been made during the last years on the mechanisms of the regulation of gene transcription by glucose in vertebrates.
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PMID:[From the glycogenic function of the liver to gene regulation by glucose]. 987 95