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 metabolic activity of the red cell glycolytic pathway hexose monophosphate shunt (HMP) with dependent glutathione system was studied in patients with hyperthyroidism (n = 10), hyperlipoproteinemia (n = 16), hypoglycemia (n = 25) and hyperglycemia (n = 23). In uncontrolled diabetics and patients with hyperthyroidism the mean value of glucose phosphate isomerase (GPI), glucose-6-phosphate dehydrogenase (G-6-PD), glutathione reductase (GR) was increased, whereas these enzyme activities were reduced in patients with hypoglycemia. Apart from a few values of hexokinase (HK) which were lower than normal the results in hyperlipoproteinemia patients remained essentially unchanged, including the intermediates such as 2,3-diphosphoglycerate (2,3-DPG), adenosine triphosphate (ATP) and reduced glutathione (GSH). While increased rates of 2,3-DPG and ATP in hypoglycemia patients were obtained, these substrates were markedly reduced in diabetics.
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PMID:Adaptation of red cell enzymes and intermediates in metabolic disorders. 12 51

The behaviour of glycolytic flux and glycolytic metabolic concentrations was studied under conditions of magnesium deficiency. The Mg-deficiency was produced in whole animals (rats) by feeding a diet almost completely free of Mg and in hemolysates of men by the addition of a chelating agent. The results show that the decrease of the free Mg-level is diminished by partial destruction of ATP and 2,3-DPG. The analysis of the control strength of the overall flux leads to the conclusion that the decrease of the glycolytic rate is caused by an inhibition of the hexokinase-phosphofructokinase-control system. The decrease of the MgATP-Complex and free Mg++-level explains the diminished phosphorylation of glucose by the hexokinase. The ATP-inhibition of the phosphofructokinase is amplified by a small increase of free ATP-concentration and a simultaneous decrease of the Fru-6P-level. The increase of the PEP-level is caused by the diminished free Mg++ and MgATP-complex and does not demonstrate a larger control strength of the pyruvate kinase.
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PMID:[Control of glycolysis in magnesium deficiency: studies on intact red cells and hemolysates]. 14 77

15 cases of congenital haemolytic anaemia have thus far been attributed to hexokinase (HK) deficiency in erythrocytes. We report some clinical, biochemical and genetic findings from 5 members of a Finnish family with this deficiency. The proband, a 1-year-old girl, was the only patient with anaemia. All subjects had either mild or marked reticulocytosis. Red cell ATP levels were at the lower range of normal in all subjects and 2,3-DPG was abnormally low in one. The activities of red cell enzymes, other than HK, were within or above the normal range, respectively. The Km-values for glucose and fructose were elevated (ATP normal) in the subjects with HK deficiency. We speculate that the family represents heterozygosity of a mutant allele and that there is phenotypic variation associated with the HK mutant. The locus might be subject to mutations which lead to a variety of HK variants and to a spectrum of diseases. This point of view is in accordance with the overwhelming variation of reaction kinetics and metabolic effects of this and other reported cases.
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PMID:Hexokinase deficiency in erythrocytes: a new variant in 5 members of a Finnish family. 45 52

An 11-yr-old child with mild chronic hemolytic anemia was found to have decreased red cell hexokinase activity in spite of the reduced mean age of her red cell population. Similar decreases in red cell hexokinase activity were documented in the patient's parents and in one sib. The red cells were morphologically normal. Red cell 2,3-DPG levels were normal and ATP and glucose-6-phosphate levels were diminished. The kinetic properties, electrophoretic mobility, and thermal stability of the residual red cell hexokinase were normal or nearly so. Glucose consumption of the hexokinase-deficient cells was not appreciably decreased, probably because less of the potent inhibitor glucose-6-phosphate was present in the erythrocytes. It is likely, although not certain, that in this patient nonspherocytic hemolytic anemia resulted from hexokinase deficiency.
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PMID:Hereditary nonspherocytic hemolytic anemia and hexokinase deficiency. 63 52

In a theoretical study the influence of hemoglobin and Mg-ions as binding partners of red cell 2,3-diphosphoglycerate and ATP was investigated. Free hemoglobin may be an efficient competitor of Mg2+ for the ligand ATP. At conditions which favour hemoglobin as binding partner (i.e. desoxygenation, low medium pH and incubation temperature, as in blood preservation) up to 95% of the whole cellular ATP (ca. 2mM in cell water) may be bound to hemoglobin (ca. 7 mM). This binding is largely prevented in the presence of physiological amounts of diphosphoglycerate (ca. 7 mM) which is in excess and has a higher binding affinity to hemoglobin. Therefore, diphosphoglycerate keeps ATP (MgATP) in cell water solution at conditions in which Hb would trop it in the presence of Mg2+ (ca. 3mM). It can be calculated that, by lack of free MgATP, the activity of hexokinase within the cell drops by a factor of greater than 10 when diphosphoglycerate is metabolized. This indirect activation by diphosphoglycerate of hexokinase is operative at free concentrations of DPG far below those which exert the well known excess inhibitory effect on hexokinase and phosphofructokinase. In a model study, the activation by diphosphoglycerate of the initial two-kinase stage was introduced into a simplified kinetic model of glycolysis. A pronounced hysteresis loop of the stationary concentrations of ATP and diphosphoglycerate was produced indicating the existence of several stationary states, one with high ATP and high diphosphoglycerate, the other one with low values. It is demonstrated that diphosphoglycerate, being a protector of glycolysis at physiological concentrations, triggers an autocatalytic breakdown of the energy state when permitted to drop to low values.
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PMID:[Importance of binding of 2,3-diphosphoglycerate and ATP to hemoglobin for erythrocyte glycolysis: activation by 2,3-diphosphoglycerate of hexokinase at intracellular conditions]. 70 29

Erythrocytes from young type I diabetic patients (n = 11), incubated in their plasma in anaerobic conditions, exhibited higher glucose consumption than cells from controls (n = 11). This increased metabolic activity is believed to reflect erythrocyte alterations dependent on the degree of metabolic control, as glucose consumption was significantly correlated to glycosylated haemoglobin (HbA1) and to glucose levels (P < 0.05 and P < 0.01 respectively). Red cell hexokinase (HK) and pyruvate kinase (PK) activities were similar in both groups whereas phosphofructokinase (PFK) activity was slightly higher in patients' cells (P < 0.05). No difference was found between patients and controls for red cell ATP and 2.3 diphosphoglycerate (2.3 DPG) levels. However, the concentrations of these glycolytic products seem also closely related to the glucose homeostasis in diabetes. Indeed, within the diabetic group, ATP levels showed a negative relationship with glucose level (P < 0.05) and 2.3 DPG a positive relationship with HbA1 (P < 0.05). In conclusion, higher glycolytic activity is present in young diabetic red cells. This activity as well as ATP and 2.3 DPG levels are related to the degree of short- or long-term diabetic control. These findings stress the importance of a careful metabolic control to avoid haematological disturbances.
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PMID:Erythrocyte metabolic alterations in type I diabetes: relationship to metabolic control. 144 91

Selected aspects of the metabolism of Plasmodium falciparum are reviewed, but conclusions based on the study of other species of plasmodia are intentionally not included since these may not be applicable. The parasites increase glucose consumption 50-100 fold as compared to uninfected red cells; most of the glucose is metabolized to lactic acid. The parasite contains a complete set of glycolytic enzymes. Some enzymes such a hexokinase, enolase and pyruvate kinase are vastly increased over corresponding levels in uninfected red cells. However, the pathway for synthesizing 2,3-diphosphoglycerate (2,3-DPG) is absent. Parasitized red cells show a decline in the concentration of 2,3-DPG which may function as an inhibitor for certain essential enzyme pathways. Pentose shunt activity is increased in absolute terms, but as a percent of total glucose consumption, there is a decrease during parasite infection of the red cell. The parasite contains a gene for G6PD and can produce a small quantity of parasite-encoded enzyme. It is not clear if the production of this enzyme can be up-regulated in G6PG deficient host red cells. The NADPH normally produced by the pentose shunt can be obtained from other parasite pathways (such as glutamate dehydrogenase). NADPH may subserve additional needs in the infected red cell such as driving diribonucleotide reductase activity--a rate limiting enzyme in DNA synthesis. The role of NADPH in protecting the parasite-red cell system against oxidative stress (via glutathione reduction) remains controversial. Parasitized red cells contain about 10 times more NAD(H) than uninfected red cells, but the NADP(H) content is unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasmodium falciparum carbohydrate metabolism: a connection between host cell and parasite. 225 22

Normal fetal ranges for red cell glycolytic intermediates at 18-24 weeks gestation, which are useful as reference values for the prenatal diagnosis of erythroenzymopathies, were established for the first time. Characteristic increases in glucose-6-phosphate (G6P), fructose-6-phosphate (F6P) and particularly fructose-1,6-diphosphate (FDP) suggest that there is no metabolic block at the phosphofructokinase (PFK) step of glycolysis as previously suggested by others for premature infants on the first day of life. Neither reticulocytosis nor anaemia consistently led to further increases in the early metabolites as occurs in adults. However, very large increases in G6P, F6P and particularly FDP may occur independently of anaemia and reticulocytosis. This suggests that activation of hexokinase (HK) and/or PFK can take place as in adults but the stimulus is probably different to adults. The 2,3-DPG in normal fetuses is higher than in adults and increases still further in anaemic fetuses with or without transfusion of adult blood. The pattern of intermediates found in the fetus suggests that the controlling mechanism for the increased 2,3-DPG may be an in vivo relative preponderance of PFK activity over that of pyruvate kinase (PK) rather than regulation of HK as proposed for adult subjects with anaemia or high altitude hypoxia.
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PMID:Red cell glycolytic intermediates in normal, anaemic and transfused human fetuses. 260 26

The effects of vitamin B6 on erythrocyte metabolism, erythrocyte hemoglobin O2 affinity (P50), and nonenzymatic glycosylation were studied in 15 Caucasian men with type II (non-insulin-dependent) diabetes mellitus. A control group of 13 healthy Caucasian men was also evaluated. Before treatment, diabetic subjects had low mean cell hemoglobin concentration values and increases in both erythrocyte 2,3-diphosphoglycerate (2,3-DPG) levels and erythrocyte hexokinase activities. Although all three of these changes are associated with a decrease in hemoglobin O2 (Hb-O2) affinity, P50 values were normal in diabetic subjects. Moreover, P50 values normalized to pH 7.4 (P50(7.4] were inversely related to the level of glycosylated hemoglobin (HbA1c). Both erythrocyte 2,3-DPG and erythrocyte ATP were also inversely related to HbA1c. Vitamin B6 nutriture, as determined by erythrocyte aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, was normal in all diabetic subjects before vitamin B6 therapy. Nonetheless, HbA1c levels decreased after 6 wk of treatment with 150 mg/day pyridoxine and increased again during placebo administration. These changes were not explained by changes in fasting blood glucose. Pyridoxine therapy also decreased P50(7.4) values and increased erythrocyte AST and ALT activities but had no effect on 2,3-DPG, ATP, or the activities of hexokinase, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase. These observations suggest that 1) nonenzymatic glycosylation may play a role in regulating both erythrocyte metabolism and Hb-O2 affinity in diabetic subjects, and 2) vitamin B6 therapy may modify nonenzymatic glycosylation of hemoglobin in this population.
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PMID:Erythrocyte O2 transport and metabolism and effects of vitamin B6 therapy in type II diabetes mellitus. 273 64

The erythrocyte metabolism of two patients with nonspherocytic hemolytic anemia caused by a hexokinase deficiency, and a pyruvate kinase deficiency, respectively, were studied with NMR. The complexing of ATP and 2,3-diphosphoglycerate (2,3-DPG) with Mg2+ and hemoglobin (Hb) was determined using 31P-NMR on oxygenated and deoxygenated cells to investigate the influences of these enzyme defects on intracellular magnesium distribution and on Hb oxygen dissociation. In the pyruvate kinase-deficient red blood cells, the 2,3-DPG concentration was almost twice the normal value and the ATP concentration was near the lower limit of the normal range. In the hexokinase-deficient red cell population, the predominance of young cells masked the deficiency. Therefore, reticulocyte control cells were included in this study. In the oxygenated pyruvate kinase-deficient cells, the fraction of ATP that is complexed to magnesium as well as the free Mg2+ concentration were normal, despite the abnormal concentration of 2,3-DPG. In the deoxygenated cells the free Mg2+ concentration was lower than in normal cells. The fraction of Hb complexed with 2,3-DPG was higher than normal in both oxygenated and deoxygenated pyruvate kinase-deficient cells, in accordance with the high p50 of the oxygen-hemoglobin dissociation curve. In hexokinase-deficient cells, two major abnormalities are found: when the cells were deoxygenated, the concentration of ATP and 2,3-DPG fell. This was not observed for any other sample and could, therefore, be a consequence of the hexokinase deficiency. Despite almost normal levels of magnesium-binding metabolites, the free Mg2+ concentration in oxygenated and deoxygenated cels is much lower than in normal cells. This could be a cell-age-related phenomenon, since lower free Mg2+ concentrations were also found in reticulocyte control cells.
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PMID:Intracellular free magnesium and phosphorylated metabolites in hexokinase- and pyruvate kinase-deficient red cells measured using 31P-NMR spectroscopy. 292 Jan 77


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