Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ;8+16' feeding schedule (8h feeding and 16h without food in each 24h cycle) was applied to nursing mother rats to study enzyme development in neonatal rats in the absence of solid food. A ;16+8' suckling schedule (16h with the mother and 8h while the mother is fed in a separate cage) was used to show that the increases in pyruvate kinase, glucokinase and aldolase B activities that occur in the late suckling period of liver development do not require the intake of solid food at this time. Their activities may, however, be modulated by the composition of the diet at the time of weaning. Adaptation to the composition of the diet can occur within one feeding period, and to the periodicity of food provision in one or two feeding periods. In the early neonatal period, diurnal rhythms of tyrosine aminotransferase, liver glycogen and glucokinase are either greatly suppressed or absent, but develop rapidly after weaning. Food-dependent rhythms of glycogen and tyrosine aminotransferase were included in the late suckling period (day 14).
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PMID:Diurnal rhythms of hepatic carbohydrate metabolism during development of the rat. 415 26

The effect of physical training on insulin release and glucose utilization by perifused islets and on liver glucokinase activity was examined in rats that exercised spontaneously by running (in wheel cage) up to 4-6 mi/day for 36 +/- 4 days and in sedentary controls kept in standard cages. Perifusion of islets with 4 mM glucose resulted in comparable rates of insulin release from islets obtained from trained and sedentary control rats. In contrast, when the perifusion glucose concentration was raised to 10 mM, the biphasic increase in insulin release was 40-50% lower in the trained rats as compared with untrained rats. This decrease in glucose-stimulated insulin release occurred in the face of comparable rates of glucose utilization by islets from control and trained rats. Glucose phosphorylation by liver homogenates from trained rats was reduced at all concentrations of glucose examined (0.5-100 mM). The calculated glucokinase activity was diminished by 40%, whereas hexokinase activity was decreased by 15% in the livers from trained rats. We conclude that 1) hypoinsulinemia induced by exercise training is due to decreased sensitivity of the beta-cell to the stimulant action of glucose independent of changes in islet cell utilization of glucose, and 2) exercise training results in a diminution of liver glucokinase activity that may be a consequence of the hypoinsulinemia.
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PMID:Influence of physical training on insulin release and glucose utilization by islet cells and liver glucokinase activity in the rat. 675 63

Recent investigation of somatic variations of allosterically regulated proteins in cancer genomes suggested that variations in glucokinase (GCK) might play a role in tumorigenesis. We hypothesized that somatic cancer-associated GCK variations include in part those with activating and/or stabilizing effects. We analyzed the enzyme kinetics and thermostability of recombinant proteins possessing the likely activating variations and the variations present in the connecting loop I and provided the first experimental evidence of the effects of somatic cancer-associated GCK variations. Activating and/or stabilizing variations were common among the analyzed cancer-associated variations, which was in strong contrast to their low frequency among germinal variations. The activating and stabilizing variations displayed focal distribution with respect to the tertiary structure, and were present in the surroundings of the heterotropic allosteric activator site, including but not limited to the connecting loop I and in the active site region subject to extensive rearrangements upon glucose binding. Activating somatic cancer-associated variations induced a reduction of GCK's cooperativity and an increase in the affinity to glucose (a decline in the S0.5 values). The hotspot-associated variations, which decreased cooperativity, also increased the half-maximal inhibitory concentrations of the competitive GCK inhibitor, N-acetylglucosamine. Concluded, we have provided the first convincing biochemical evidence establishing GCK as a previously unrecognized enzyme that contributes to the reprogramming of energy metabolism in cancer cells. Activating GCK variations substantially increase affinity of GCK to glucose, disrupt the otherwise characteristic sigmoidal response to glucose and/or prolong the enzyme half-life. This, combined, facilitates glucose phosphorylation, thus supporting glycolysis and associated pathways.
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PMID:First evidence of changes in enzyme kinetics and stability of glucokinase affected by somatic cancer-associated variations. 3059 Jan 53