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)

1. The oxidation of butyrate, hexanoate and octanoate by rat-liver mitochondria suspended in a tris-potassium chloride medium in the presence of malate and serum albumin has been investigated. 2. The oxidation of butyrate to acetoacetate was markedly decreased by the addition of a system competitive for ATP (hexokinase-glucose). 3. Serum albumin or tricarboxylic acid-cycle intermediates prevented the inhibition by hexokinase and in their presence a greater proportion of the oxygen consumption was contributed by the tricarboxylic acid cycle. The results suggest that the energy supply for fatty acid activation is either compartmentalized in a spatial or kinetic sense or there exists a special activating mechanism not involving ATP. 4. Malate and other tricarboxylic acid-cycle intermediates caused substantial reduction (to beta-hydroxybutyrate) of the acetoacetate formed during the oxidation of butyrate, hexanoate and octanoate.
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PMID:The effect of hexokinase and tricarboxylic acid-cycle intermediates on fatty acid oxidation and formation of ketone bodies by rat-liver mitochondria. 594 42

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

Utilization of the tricarboxylic acid (TCA) cycle intermediates, L-malic acid and succinic acid, by the yeast Pachysolen tannophilus is repressed in the presence of glucose. Strains of P. tannophilus containing mutations in two hexokinases and a glucokinase were characterized for growth on glucose plus L-malic acid or succinic acid. Increased specific utilization rates of malic acid and succinic acid in the presence of glucose were observed in mutants containing a lesion in hexokinase A, an enzyme associated with catabolite repression. Such derepressed mutants may have application in winemaking in which utilization of a major grape acid, L-malic acid, is often desirable for acidity reduction.
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PMID:Derepressed utilization of L-malic acid and succinic acid by mutants of Pachysolen tannophilus. 924 68

In the apple variety 'Usterapfel', there are two known genotypes, which differ in malic acid content. One hundred days after full bloom, low-acid fruit (LA-fruit) contained 125 micromolg(-1) dry matter (DW) of malate, while the high-acid genotype (HA-fruit) reached levels up to 627 micromolg(-1) DW. There was no difference in the catalytic activity of enzymes involved in malate metabolism, such as PEPcarboxylase, malate dehydrogenase, and NADP malic enzyme. After [14C]glucose incorporation into the excised tissue of either genotype, the organic acid fraction was labeled to approximately the same extent. Furthermore, uptake of [14C]malate was significantly lower in excised tissue of LA-fruit. These findings suggest that low malate content in LA-fruit is the result of a restricted ability to accumulate malate in apple parenchyma cells. The different ability to accumulate malate had a pronounced effect on overall carbon partitioning. However, the rate of respiration and the rate of malate synthesis was similar in both genotypes. In HA-fruit, the glycolytic flux through pyruvate kinase was increased to compensate for the carbon that accumulated in the vacuole as malate. Since malate storage in the LA-fruit was restricted, it was more easily available for gluconeogenesis, and was correlated with a three-times higher activity of PEPcarboxykinase. LA-fruit showed higher concentrations of ATP, which stimulated Glc6P and fructose-6-phosphate formation. The elevated hexosephosphate content led to an enhanced partitioning of carbon into starch (+40%), hemicellulose (+104%), and sucrose (+40%) in more mature fruit. The activation of carbohydrate synthesis resulted in a significant drop in glucose-1-phosphate (Glc1P). To meet the increased demand for Glc1P, the activities of neutral and acid invertase, hexokinase, and phosphoglucomutase were higher in LA-fruit. Glucose was a more versatile substrate for this metabolic route than was fructose. It was also evident that glycolytic flux in apple was dependent on glucose level, and that the reaction catalysed by phosphoglucomutase contributed to the regulation of carbon partitioning between malate and carbohydrate polymers.
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PMID:Carbohydrate metabolism in two apple genotypes that differ in malate accumulation. 1549 4

Sorbitol and sucrose are major products of photosynthesis distributed in apple trees (Malus domestica Borkh. cv. "Greensleeves") that affect quality in fruit. Transgenic apple plants were silenced or up-regulated for sorbitol-6-phosphate dehydrogenase by using the CaMV35S promoter to define the role of sorbitol distribution in fruit development. Transgenic plants with suppressed sorbitol-6-phosphate dehydrogenase compensated by accumulating sucrose and starch in leaves, and morning and midday net carbon assimilation rates were significantly lower. The sorbitol to sucrose ratio in leaves was reduced by approximately 90% and in phloem exudates by approximately 75%. The fruit accumulated more glucose and less fructose, starch, and malic acid, with no overall differences in weight and firmness. Sorbitol dehydrogenase activity was reduced in silenced fruit, but activities of neutral invertase, vacuolar invertase, cell wall-bound invertase, fructose kinase, and hexokinase were unaffected. Analyses of transcript levels and activity of enzymes involved in carbohydrate metabolism throughout fruit development revealed significant differences in pathways related to sorbitol transport and breakdown. Together, these results suggest that sorbitol distribution plays a key role in fruit carbon metabolism and affects quality attributes such as sugar-acid balance and starch accumulation.
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PMID:Silencing leaf sorbitol synthesis alters long-distance partitioning and apple fruit quality. 1713 42

Microbial fermentation was widely explored to produce malic acid. Previously, Aspergillus niger has been successfully engineered, and a high titer of malic acid was achieved with strain S575, but it also produced a high level of byproduct citric acid. Here, the capability of A. niger in malic acid biosynthesis was further improved by eliminating the accumulation of citric acid and enhancing glycolytic flux. Characterization of variant mutants suggested that disruption of cexA, a gene encoding citric acid transporter located on cell membrane, abolished citric acid accumulation. However, cexA-deficient strain S895 showed significantly decreased malic acid production. Further analysis of S895 indicated that the transcription level of genes involved in glucose transportation and glycolytic pathway was significantly reduced, and the corresponding enzyme activity was also lower than those of S575. Individual overexpression of genes encoding glucose transporter MstC and key enzymes (hexokinase HxkA, 6-phosphofructo-2-kinase PfkA, and pyruvate kinase PkiA) involved in irreversible reactions of glycolic pathway increased malic acid production. Accordingly, genes of mstC, hxkA, pfkA, and pkiA were overexpressed altogether in S895, and the resultant strain S1149 was constructed. The titer of malic acid in fed-batch fermentation with S1149 reached 201.13 g/L. Compared with S575, the byproduct of citric acid was completely abolished in S1149, and the ratio of malic acid/glucose was increased from 1.27 to 1.64 mol/mol, the highest yield reported so far, and the fermentation period was shortened from 9 to 8 days. Thus, a strain with great industrial application potential was developed by engineering nine genes in A. niger, and a pilot fermentation technology was exploited.
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PMID:Improved Production of Malic Acid in Aspergillus niger by Abolishing Citric Acid Accumulation and Enhancing Glycolytic Flux. 3237 64