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 importance and the value of applying metabolic-control logic to the question of fuels, their rates of utilization and their significance to the process of proliferation are presented. Application of the recently developed quantitative theory of metabolic control of branched pathways provides a hypothesis to account for the high rate of both glycolysis and glutaminolysis in lymphocytes, macrophages and, in particular, in tumor cells. Both glycolysis and glutaminolysis provide metabolic intermediates for biosynthetic pathways: for example, glucose-6-phosphate for the formation of ribose-5-phosphate, and glutamine, ammonia and aspartate which are required for the synthesis of purine and pyrimidine nucleotides. However, the rates of both glycolysis and glutaminolysis are greatly in excess (greater than 400-fold) of the requirements for the biosynthetic processes. If energy formation per se was the major reason for the high rate of glutamine utilization, why is the oxidation only partial? The ability of the cell to divide will require the synthesis of all the DNA, RNA, phospholipids, etc., at precise times in the cell cycle. Hence very high and accurate sensitivity of the processes that provide the precursors for these compounds to their specific regulators will be expected. Maintenance of high rates of glycolysis and glutaminolysis at all times can be seen therefore as a device to allow intermediates to be "tapped off" at the precise rate required whenever they are needed for biosynthesis. Maximal activities of some key enzymes of glycolysis, the tricarboxylic acid cycle and glutaminolysis from a variety of normal, neoplastic and suppressed cells are presented. The relative activities of hexokinase and 6-phosphofructokinase suggest that, particularly in neoplastic cells, in which the capacity for glucose transport is high, hexokinase could approach saturation in respect to intracellular glucose; consequently, hexokinase and phosphofructokinase could play an important role in the regulation of glycolytic flux in these cells. The activity of pyruvate kinase is considerably higher in tumorigenic cells than in nontumorigenic cells and higher in metastatic cells than in tumorigenic cells: for nontumorigenic cells the activities range from 28.4 to 574, for tumorigenic cells from 899 to 1280, and for metastatic cells from 1590 to 1627 nmol/min per mg of protein. The ratio of pyruvate kinase activity to 2 x phosphofructokinase activity is very high in neoplastic cells. The mean is 22.4 for neoplastic cells, whereas for muscle from 60 different animals it is only 3.8.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Application of metabolic-control logic to fuel utilization and its significance in tumor cells. 187 89

The specific activities of each of the enzymes of the classical pentose phosphate pathway have been determined in both cultured procyclic and bloodstream forms of Trypanosoma brucei. Both forms contained glucose-6-phosphate dehydrogenase (EC 1.1.1.49), 6-phosphogluconolactonase (EC 3.1.1.31), 6-phosphogluconate dehydrogenase (EC 1.1.1.44), ribose-5-phosphate isomerase (EC 5.3.1.6) and transaldolase (EC 2.2.1.2). However, ribulose-5-phosphate 3'-epimerase (EC 5.1.3.1) and transketolase (EC 2.2.1.1) activities were detectable only in procyclic forms. These results clearly demonstrate that both forms of T. brucei can metabolize glucose via the oxidative segment of the classical pentose phosphate pathway in order to produce D-ribose-5-phosphate for the synthesis of nucleic acids and reduced NADP for other synthetic reactions. However, only procyclic forms are capable of using the non-oxidative segment of the classical pentose phosphate pathway to cycle carbon between pentose and hexose phosphates in order to produce D-glyceraldehyde 3-phosphate as a net product of the pathway. Both forms lack the key gluconeogenic enzyme, fructose-bisphosphatase (EC 3.1.3.11). Consequently, neither form should be able to engage in gluconeogenesis nor should procyclic forms be able to return any of the glyceraldehyde 3-phosphate produced in the pentose phosphate pathway to glucose 6-phosphate. This last specific metabolic arrangement and the restriction of all but the terminal steps of glycolysis to the glycosome may be the observations required to explain the presence of distinct cytosolic and glycosomal isoenzymes of glyceraldehyde-3-phosphate dehydrogenase and phosphoglycerate kinase. These same observations also may provide the basis for explaining the presence of cytosolic hexokinase and phosphoglucose isomerase without the presence of any cytosolic phosphofructokinase activity. The key enzymes of the Entner-Doudoroff pathway, 6-phosphogluconate dehydratase (EC 4.2.1.12) and 2-keto-3-deoxy-6-phosphogluconate aldolase (EC 4.1.2.14) were not detected in either procyclic or bloodstream forms of T. brucei.
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PMID:The enzymes of the classical pentose phosphate pathway display differential activities in procyclic and bloodstream forms of Trypanosoma brucei. 292 7

The purpose of this work was to study the activity of the key enzymes of intermediate metabolism in cultures belonging to several genera of coryneform bacteria, either capable or incapable of producing adenylic nucleotides from exogenous adenine. The results are indicative of an increase in the activity of polyphosphate-dependent hexokinase by the stationary growth phase in corynebacteria; in contrast, the activity of the enzyme in coryneform bacteria (rhodococci) remained unchanged. The absence of transketolase activity in the producing strains seems to account for the overproduction of ribose-5-phosphate.
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PMID:[Metabolic mechanism of adenine nucleotide synthesis from exogenous adenine in corynebacteria]. 679 55

Meloche, H. P., Jr. (Northern Regional Research Laboratory, Peoria, Ill.). Enzymatic utilization of glucose by a basidiomycete. J. Bacteriol. 83:766-774. 1962.-Cell-free extracts of acetone-dried Lactarius torminosus NRRL 2900 were prepared. These extracts contained hexokinase. They also contained triphosphopyridine nucleotide (TPN)-specific glucose-6-phosphate dehydrogenase and catalyzed the reduction of TPN in the presence of d-fructose-6-phosphate, 6-phospho-d-gluconic acid (6PG), and d-ribose-5-phosphate (R5P). Aged preparations oxidized d-glucose-6-phosphate (G6P) to 6PG, whereas fresh preparations oxidized G6P to a pentose with the uptake of 1 mumole of O(2) and the evolution of 1 mumole of CO(2) per mumole of G6P. Evidence for the action of transketolase in the metabolism of R5P by cell-free extracts was obtained.Cell-free preparations lacked hexosediphosphate enzymes. Triosephosphate isomerase and F6P kinase could not be demonstrated; however, aldolase activity was present. Evidence is presented for the conversion of d-glyceraldehyde-3-phosphate to pyruvate. In addition, phosphohexoisomerase was demonstrated. It appears that a hexosemonophosphate pathway operates in L. torminosus extracts and may be the major mechanism of glucose dissimilation in this organism.
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PMID:Enzymatic utilization of glucose by a basidiomycete. 1447 42