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)

In order to find the markers of the toxicity of the autoxidized lipids in the liver, rats were given a lethal amount of secondary autoxidation products of linoleic acid (400 mg/rat/day for 3 days) and then changes in the hepatic metabolic functions were analyzed. A decrease in acetyl-CoA level to half caused by the depletion of CoASH was reported in an associated paper (J. Nutr. Sci. Vitaminol., 35, 11-23, 1989). Citrate, isocitrate, and 2-oxoglutarate also decreased to half the level of those of the control group. Reduction in isocitrate dehydrogenase activity was only 25%, while NADH2 and ATP levels remained unchanged. Thus, the reduction in the citrate cycle activity was due to the decrease in acetyl-CoA. The activity of mitochondrial succinate dehydrogenase was decreased to 1/5. Other appreciable changes were depletion of glucose 6-phosphate and fructose 6-phosphate, accumulation of glucose 1-phosphate, reductions in hexokinase, phosphofructokinase, glucose-6-phosphatase, phosphoglucomutase, and phosphogluconate dehydrogenase activities, and decrease in the NADPH2 level. It was considered that these changes were caused by the depletion of glucose 6-phosphate whose synthetic pathways were abnormal. Therefore, the markers of the hepatotoxicity of secondary products were the changes in the CoASH level and the activities of succinate dehydrogenase and synthetic pathways for glucose 6-phosphate.
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PMID:Succinate dehydrogenase and synthetic pathways of glucose 6-phosphate are also the markers of the toxicity of orally administered secondary autoxidation products of linoleic acid in rat liver. 254 8

1. The activities of gluconeogenic and glycolytic enzymes and the concentrations of citrate, ammonia, amino acids, glycogen, glucose 6-phosphate, acetyl-CoA, lactate and pyruvate were measured in kidney cortex of normal, diabetic, cortisone-treated and growth hormone-treated rats. 2. In kidney cortex of diabetic, cortisone-treated and growth hormone-treated rats the activities of glucose 6-phosphatase (EC 3.1.3.9), fructose 1,6-diphosphatase (EC 3.1.3.11) and phosphopyruvate carboxylase (EC 4.1.1.32) were increased. 3. The activities of glutamate dehydrogenase (EC 1.4.1.3), alanine aminotransferase (EC 2.6.1.2), aspartate aminotransferase (EC 2.6.1.10) and pyruvate carboxylase (EC 6.4.1.1) were increased in diabetic and cortisone-treated rats. In growth hormone-treated rats the activity of aspartate aminotransferase was depressed but those of the other three enzymes were unchanged. 4. The activity of hexokinase (EC 2.7.1.1) was not altered in any of these conditions. Phosphofructokinase (EC 2.7.1.11) activity was depressed only in growth hormone-treated rats. Pyruvate kinase (EC 2.7.1.40) activity was depressed in cortisone-treated and growth hormone-treated rats but unchanged in diabetic rats. 5. Amino acids, acetyl-CoA and glucose 6-phosphate contents were increased in rat kidneys in all these three conditions. Ammonia content was increased in diabetic and cortisone-treated rats but was markedly diminished in growth hormone-treated rats. 6. The [lactate]/[pyruvate] ratio was elevated in diabetic and cortisone-treated rats but unchanged in growth hormone-treated rats. Citrate content was increased in the kidney cortex of diabetic and growth hormone-treated rats but was unchanged in cortisone-treated rats. The activity of ATP citrate lyase (EC 4.1.3.8) was depressed in diabetic and growth hormone-treated rats but was increased in cortisone-treated rats. 7. Glycogen content was moderately elevated in growth hormone-treated rats and markedly elevated in diabetic rats, whereas no change in glycogen content was observed in cortisone-treated rats. Glycogen synthetase (EC 2.4.1.11) activity was unchanged in all these three conditions. Phosphorylase (EC 2.4.1.1) activity was not affected in cortisone-treated rats but was depressed in diabetic and growth hormone-treated rats.
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PMID:Evaluation of the rate-limiting steps in the pathway of glucose metabolism in kidney cortex of normal, diabetic, cortisone-treated and growth hormone-treated rats. 434 56

A single glucose-phosphorylating enzyme has been detected and purified from the citric acid accumulating fungus Aspergillus niger. The enzyme was formed constitutively, and high activities were formed on glucose and sucrose as carbon sources. Highest activities were formed during growth on high concentrations of glucose or sucrose. The enzyme, purified about 600-fold from cell-free extracts prepared from glucose-grown mycelia, gave a double band in denaturing (SDS)-polyacrylamide gel electrophoresis. Tryptic peptide patterns suggest that the lower molecular weight band was the product of either C- or N-terminal truncation. The specific activity of the enzyme was about 40 and 35 mumol/min and mg protein with glucose and fructose as substrates, respectively. The affinity for glucose was about 10(3)-fold higher than for fructose. The subunit molecular weight was 50,000 and the molecular weight of the native protein was 100,000 by gel permeation chromatography. Of the reaction products ADP, but not glucose 6-phosphate, inhibited hexokinase activity. Citrate inhibited (K1 0.15 mM) non-competitively with respect to both glucose and ATP, which was not due to Mg(2+)-chelation. 2-Deoxyglucose resistant mutant strains of A. niger were isolated which showed decreased growth rate and activity of hexokinase during growth on glucose, while their growth on fructose and hexokinase activities were comparable to the parent strain. They displayed a reduced rate of citric acid accumulation. It is concluded that the synthesis of very high hexokinase activities may counteract citrate inhibition, thereby guaranteeing a high glycolytic flux during citric acid accumulation.
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PMID:Characterization and regulatory properties of a single hexokinase from the citric acid accumulating fungus Aspergillus niger. 803 43

Rabbit tibialis anterior muscles were stimulated continuously at 10 Hz for periods ranging from 2 min to 96 h and were analyzed for energy reserves and metabolic intermediates. Glycogen, ATP and phosphocreatine fell rapidly during the first 5 min of stimulation. Glycogen continued to fall to very low levels, whereas ATP and phosphocreatine rose, reaching 70% of control by 1 h, despite ongoing stimulation. After 2 h, glycogen also increased, regaining control levels in 4 days. Glucose rose to 4.5 times control in 30 min and still exceeded 2.5 times control at 24 h. In the first 2 min, glycolytic intermediates, glucose 6-phosphate (G-6-P), fructose 1,6-bisphosphate, lactate, and pyruvate more than doubled and then returned to control levels or below. Malate and 3-glycerophosphate rose 600 and 200%, respectively. Both of these compounds participate in shuttling reducing equivalents from cytoplasm into mitochondria. Citrate and alpha-ketoglutarate underwent much more modest changes. Glucose 1,6-bisphosphate (G-1,6-P2) fell to one-third of control by 2 h and then rose dramatically at 4 h. At 4 days it was still twice control. The 6-phosphogluconate (6PG) doubled at 2 min, then rose to 12 times control at 2 h, fell somewhat, and peaked at 16 times control at 24 h. Aspartate and alanine both exhibited a biphasic rise in concentration, whereas glutamate fell to 30% in 15 min and rose slowly after 4 h. The rise in glucose was interpreted to be the consequence of rapid glycogenolysis together with inhibition of hexokinase by G-1,6-P2 and elevated G-6-P. Paradoxically, glycogen resynthesis apparently occurred when the glycogen synthase stimulator, G-6-P, was very low, and the glycolysis stimulator, G-1,6-P2, was high. Although G-1,6-P2 is an inhibitor of 6PG dehydrogenase, the timing of the changes in G-1,6-P2 and 6PG levels suggests that the accumulation of 6PG was initiated by some other influence.
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PMID:Changes in ATP, phosphocreatine, and 16 metabolites in muscle stimulated for up to 96 hours. 889 22

A second hexokinase (EC 2.7.1.1) was obtained from pea seed (Pisum sativum L. var. Progress No. 9) extracts. The enzyme, termed hexokinase II, had a high affinity (K(m), 48 micromolar) for glucose and a relatively low affinity (K(m), 10 millimolar) for fructose. The K(m) for MgATP was 86 micromolar. Mg(2+) was required for activity, but excess Mg(2+) was inhibitory. MgADP inhibited hexokinase II. The addition of salts of monovalent cations increased hexokinase II activity. Al(3+) was a strong inhibitor of the enzyme at pH 6.6 but not at the optimum pH (8.2). Citrate and 3-phosphoglycerate activated pea seed hexokinase II at pH 6.6, probably by coordinating with aluminum present as a contaminant in commercial ATP. The properties of hexokinase II are compared with those of the other three hexose kinases obtained from pea seed extracts. The possible role of these enzymes in plant carbohydrate metabolism is discussed.
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PMID:Hexokinase II of Pea Seeds. 1666 62