Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

The effect of cataractogenesis on the behavior of some enzymes involved in glucose metabolism was examined histochemically both in human lenses and in rat lenses from rats with alloxan-induced diabetes. Several modifications in the currently available techniques were made in order to localize glucose-6-phosphate dehydrogenase, aldose reductase, sorbitol dehydrogenase, hexokinase and ketohexokinase in ocular lens. Human cataractous lenses showed a precipitous drop in glucose-6-phosphate dehydrogenase activity, whereas the lenticular tissues of alloxan-treated rats showed a gradual decrease of this enzyme with the prolongation of diabetes. Aldose reductase activity increased in hypermature and senile diabetic cataracts, whereas sorbitol dehydrogenase activity decreased in these lenses. Similarly, in alloxan-diabetic rat lenses the activity of aldose reductase increased while that of sorbitol dehydrogenase decreased with the prolongation of diabetes. Attempts were made to localize hexokinase and ketohexokinase in ocular lens.
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PMID:Studies on cataractogenesis in humans and in rats with alloxan-induced diabetes. II. Histochemical evaluation of lenticular enzymes. 298 23

The longitudinal localization of nine enzymes of the carbohydrate metabolism was studied in rats fed standard or high fructose diets, two months after a reciprocal jejuno-ileal transposition. In the ileal segment transposed to jejunal location, an adaptive increase of mucosal mass was observed, but the functional characteristics of enterocytes remained the same in the case of triokinase, aldolase, triose phosphate isomerase, glucose-6-phosphate isomerase and glucose-6-phosphatase activities. In the case of ketohexokinase and hexokinase activities, the functional properties of cells tended to resemble that of jejunum, as revealed by a significant increase in the specific enzyme activity. In the jejunum transposed to the place of the ileum, the fundamental properties of enterocytes and the functional capacity of the gut were maintained except in the case of fructose-1.6-bis phosphatase and of glucose-6-phosphatase. The high fructose diet did not facilitate the re-establishment of the gradient in its normal, aboral, direction. Indeed except for glucose-6-phosphatase, the enzymes of the jejunum transposed to the place of the ileum kept a high sensitivity and the enzymes of transposed ileum a low sensitivity to dietary fructose. Our conclusion is that the response to the diet depends more on the original position of the intestinal segment than on the local nutritional conditions and therefore that the basal activity of the majority of the intracellular enzymes implicated in carbohydrate metabolism and also their regulatory systems, are an intrinsic characteristic of the intestinal cells.
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PMID:[Intestinal adaptation and enzymatic changes following reciprocal jejunoileal transposition in rats. Effects of a high-fructose diet]. 397 35

The enzyme activities involved in fructose metabolism were measured in samples of human liver. On the basis of U/g of wet-weight the following results were found: ketohexokinase, 1.23; aldolase (substrate, fructose-1-phosphate), 2.08; aldolase (substrate, fructose-1,6-diphosphate), 3.46; triokinase, 2.07; aldehyde dehydrogenase (substrate, D-glyceraldehyde), 1.04; D-glycerate kinase, 0.13; alcohol dehydrogenase (nicotinamide adenine dinucleotide [NAD]) substrate, D-glyceraldehyde), 3.1; alcohol dehydrogenase (nicotinamide adenine dinucleotide phosphate [NADP]) (substrate, D-glyceraldehyde), 3.6; and glycerol kinase, 0.62. Sorbitol dehydrogenases (25.0 U/g), hexosediphosphatase (4.06 U/g), hexokinase (0.23 U/g), and glucokinase (0.08 U/g) were also measured. Comparing these results with those of the rat liver it becomes clear that the activities of alcohol dehydrogenases (NAD and NADP) in rat liver are higher than those in human liver, and that the values of ketohexokinase, sorbitol dehydrogenases, and hexosediphosphatase in human liver are lower than those values found in rat liver. Human liver contains only traces of glycerate kinase. The rate of fructose uptake from the blood, as described by other investigators, can be based on the activity of ketohexokinase reported in the present paper. In human liver, ketohexokinase is present in a four-fold activity of glucokinase and hexokinase. This result may explain the well-known fact that fructose is metabolized faster than glucose.
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PMID:Enzymes of fructose metabolism in human liver. 438 49

By introducing fructose into the glycolysis, it is possible to stimulate ATP formation. As is the case in animal experiments, in human lenses, too, the first step in the phosphorylation to fructose-1-phosphate via the enzyme ketohexokinase. The present investigation deals with the question whether enzymes present in the lens are responsible for the further steps in fructose degradation. Particularly the aldolase isoenzyme C splits fructose-1-phosphate into glyceraldehyde and dihydroxyacetone phosphate in the same way as in glucose catabolism. Dihydroxyacetone phosphate can further be directly degraded and thus utilized to ATP formation. From glyceraldehyde, glycerol (aldose reductase) or glycerate (aldehyde dehydrogenase) can be formed. The presence of triosekinase, which phosphorylates glyceraldehyde directly to glyceraldehyde-3-phosphate, could only be determined in the lens tissue of young animals. The presence of glycerokinase (glycerol leads to glycerophosphate) could not be verified. Thus, in the lens tissue 1 ATP molecule net per fructose molecule can be formed. In older age, the glucose breakdown is limited by hexokinase and phosphofructokinase, so that the glucose, after transformation via the sorbitol pathway to fructose, can also be utilized for the energy metabolism.
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PMID:Investigations of the enzymes involved in the fructose breakdown in the cattle lens. 628 47

The glucokinase regulator (GCKR) is a 65-kDa protein that inhibits glucokinase (hexokinase IV) in liver and pancreatic islet. The role of glucokinase (GCK) as pancreatic beta cell glucose sensor and the finding of GCK mutations in maturity onset diabetes of the young (MODY) suggest GCKR as a further candidate gene for type 2 diabetes. The inhibition of GCK by GCKR is relieved by the binding of fructose-1-phosphate (F-1-P) to GCKR. F-1-P is the end product of ketohexokinase (KHK, fructokinase), which, like GCK and GCKR, is present in both liver and pancreatic islet. KHK is the first enzyme of the specialized pathway that catabolizes dietary fructose. We have isolated genomic clones containing the human GCKR and KHK genes. By fluorescent in situ hybridization (FISH), KHK maps to Chromosome (Chr) 2p23.2-23.3, a new assignment corroborated by somatic cell hybrid analysis. The localization of GCKR, originally reported by others as 2p22.3, has been reassessed by high-resolution FISH, indicating that, like KHK, GCKR maps to 2p23.2-23.3. The proximity of GCKR and KHK was further demonstrated both by two-color interphase FISH, which suggests that the two genes lie within 500 kb of each other, and by analysis of overlapping YAC and P1 clones spanning the interval between GCKR and KHK. A new microsatellite polymorphism was used to place the GCKR-KHK locus between D2S305 and D2S165 on the genetic map. The colocalization of these two metabolically connected genes has implications for the interpretation of linkage or allele association studies in type 2 diabetes. It also raises the possibility of coordinate regulation of GCKR and KHK by common cis-acting regulatory elements.
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PMID:Co-localization of the ketohexokinase and glucokinase regulator genes to a 500-kb region of chromosome 2p23. 866 30

1. During development of the sheep, the activities of UDP-glucose-alpha-glucan glucosyltransferase and UDP-glucose pyrophosphorylase and the glycogen content are highest in the liver of lambs 2 weeks old and considerably lower in liver from adult sheep. 2. The activity of hexokinase and the rate of incorporation of [(14)C]-glucose into glycogen are much lower in liver from postnatal sheep than in rat liver. 3. The activities of hexose diphosphatase and glucose 6-phosphatase and the rates of incorporation of [(14)C]pyruvate and [(14)C]propionate into glycogen increase from low levels in the liver of foetal sheep to maxima a few weeks after birth. The activities in the liver of adult sheep are slightly lower. 4. The incorporation rate of [(14)C]pyruvate into glucose has been measured in liver slices from rats, sheep and chick embryos at several ages of these animals. This pathway is active in liver from foetal sheep, embryonic chicks and postnatal rats or sheep, but is absent from the liver from foetal rats. 5. Fructose metabolism, as measured by the rates of incorporation of [(14)C]fructose into glycogen and glucose in liver slices and by assays of liver ketohexokinase, is barely detectable in the liver of foetal sheep and appears soon after birth. 6. During development of the sheep, the incorporation rate of [(14)C]galactose into glycogen in liver slices is highest in foetal sheep and decreases with increasing age of the animal. 7. These findings are discussed with reference to the changing pattern of carbohydrate metabolism during neonatal development of liver in the sheep.
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PMID:CARBOHYDRATE METABOLISM IN LIVER FROM FOETAL AND NEONATAL SHEEP. 1433 56

The presence of fructokinase (ketohexokinase) in rat pancreatic islet homogenates was previously documented. However, no information was so far available on the activity of this enzyme in islets relative to that in other tissues and on the respective contribution of insulin-producing B cells and non-B islet cells. The present study provides such an information. The activity of fructokinase, as assessed by the phosphorylation of 1.0 mM D-fructose, was compared to that of hexokinase isoenzyme(s), as measured in the presence of 1.0 mM D-glucose, and further characterized by its heat-resistance, K+ dependency and resistance to the inhibitory action of D-mannoheptulose. As judged from the results obtained in heated homogenates, the activity of fructokinase, expressed relative to protein content (nmol/min per mg protein) was highest in liver (21.5 +/- 2.5; n = 11) and lowest in parotid gland (0.16 +/- 0.09; n = 3), with in-between values in ileum (2.45 +/- 0.53; n = 3), pancreas (0.82 +/- 0.11; n = 11) and pancreatic islets (0.46 +/- 0.07; n = 6). The paired ratio between fructokinase and hexokinase isoenzyme activity was also highest in liver (548 +/- 45%; n = 8) and lowest in parotid gland (0.93 +/- 0.52%; n = 3). Such a ratio was not significantly different in pancreas, islets and purified B or non-B islet cells, with an overall mean value of 2.57 +/- 0.46% (n = 12). The present findings thus unambiguously document the presence of fructokinase activity in all cell types under consideration, except possibly parotid cells, with the following hierarchy: liver > ileum > pancreas. Relative to paired hexokinase activity, no obvious difference was found for fructokinase activity in B versus non-B islet cells.
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PMID:Fructokinase activity in rat liver, ileum, parotid gland, pancreas, pancreatic islet, B and non-B islet cell homogenates. 1646 1

Fructose reacts spontaneously with proteins in the brain to form advanced glycation end products (AGE) that may elicit neuroinflammation and cause brain pathology, including Alzheimer's disease. We investigated whether fructose is eliminated by oxidative metabolism in neocortex. Injection of [(14) C]fructose or its AGE-prone metabolite [(14) C]glyceraldehyde into rat neocortex in vivo led to formation of (14) C-labeled alanine, glutamate, aspartate, GABA, and glutamine. In isolated neocortical nerve terminals, [(14) C]fructose-labeled glutamate, GABA, and aspartate, indicating uptake of fructose into nerve terminals and oxidative fructose metabolism in these structures. This was supported by high expression of hexokinase 1, which channels fructose into glycolysis, and whose activity was similar with fructose or glucose as substrates. By contrast, the fructose-specific ketohexokinase was weakly expressed. The fructose transporter Glut5 was expressed at only 4% of the level of neuronal glucose transporter Glut3, suggesting transport across plasma membranes of brain cells as the limiting factor in removal of extracellular fructose. The genes encoding aldose reductase and sorbitol dehydrogenase, enzymes of the polyol pathway that forms glucose from fructose, were expressed in rat neocortex. These results point to fructose being transported into neocortical cells, including nerve terminals, and that it is metabolized and thereby detoxified primarily through hexokinase activity. We asked how the brain handles fructose, which may react spontaneously with proteins to form 'advanced glycation end products' and trigger inflammation. Neocortical cells took up and metabolized extracellular fructose oxidatively in vivo, and isolated nerve terminals did so in vitro. The low expression of fructose transporter Glut5 limited uptake of extracellular fructose. Hexokinase was a main pathway for fructose metabolism, but ketohexokinase (which leads to glyceraldehyde formation) was expressed too. Neocortical cells also took up and metabolized glyceraldehyde oxidatively.
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PMID:Uptake and metabolism of fructose by rat neocortical cells in vivo and by isolated nerve terminals in vitro. 2570 47

Hummingbirds are able to fuel hovering flight entirely with recently ingested glucose or fructose. Among vertebrates, several steps of sugar flux from circulation to skeletal muscle are potentially rate-limiting, including transport into muscle and subsequent phosphorylation. While capacities for glucose flux are substantial, capacities for fructose flux are comparatively low. The mechanisms underlying apparent high rates of glucose and fructose oxidation in hummingbird flight muscle remain unclear. We examined relative expression of facilitative sugar transporters (GLUTs) and enzymes of fructolysis in ruby-throated hummingbird (Archilochus colubris) tissues involved in energy homeostasis and flight, via qPCR and measured hexokinase activity in pectoralis in vitro. We hypothesized that expression of these genes was upregulated in hummingbird flight muscle compared to other vertebrates. We found that hummingbird pectoralis had high relative transcript abundance of GLUT1 and GLUT5 compared to expression profiles of other vertebrates. In particular, GLUT5 expression in pectoralis was similar to that of intestine. We demonstrated minimal relative densities of fructolytic enzymes in pectoralis, suggesting that the ketohexokinase pathway does not rapidly metabolize fructose in these muscles. Instead, we found that the capacity for phosphorylation of either glucose or fructose by hexokinase is very high in pectoralis in vitro. The contributions of individual hexokinase isoforms remain to be determined. Our results further characterize the strategies by which hummingbirds, and perhaps other nectarivores, accomplish rapid sugar flux. High transport and sugar phosphorylation capacities appear to exist in flight muscle, though the enzymatic pathways that catalyze the phosphorylation of sugar in muscle remain uncertain.
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PMID:Evidence of high transport and phosphorylation capacity for both glucose and fructose in the ruby-throated hummingbird (Archilochus colubris). 2912 75

Protein kinases regulate every aspect of cellular activity, whereas metabolic enzymes are responsible for energy production and catabolic and anabolic processes. Emerging evidence demonstrates that some metabolic enzymes, such as pyruvate kinase M2 (PKM2), phosphoglycerate kinase 1 (PGK1), ketohexokinase (KHK) isoform A (KHK-A), hexokinase (HK), and nucleoside diphosphate kinase 1 and 2 (NME1/2), that phosphorylate soluble metabolites can also function as protein kinases and phosphorylate a variety of protein substrates to regulate the Warburg effect, gene expression, cell cycle progression and proliferation, apoptosis, autophagy, exosome secretion, T cell activation, iron transport, ion channel opening, and many other fundamental cellular functions. The elevated protein kinase functions of these moonlighting metabolic enzymes in tumor development make them promising therapeutic targets for cancer.
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PMID:Metabolic Kinases Moonlighting as Protein Kinases. 2946 70


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