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)

Serum copper levels (SCL) which are concomitantly related to red blood cell free copper are significantly increased in some malignant lymphomas in the phase of activity. This results in a profound inhibition of red cell key glycolytic enzymes, hexokinase (Hx) being the most sensitive. Fifteen patients (eight with Hodgkin's disease and seven with non-Hodgkin's lymphoma) were studied for serum and red cell copper concentrations and Hx activity. The mean red cell life span was determined using 51Cr labelled red cells. The resulting data shows that in active disease an increase in SCL was associated with a decrease in Hx activity and a shortened red cell survival. In these cases there was no evidence of autoimmune phenomena or of direct bone marrow involvement by the disease. It is suggested that the increase in copper levels results in a shortened red cell life span through a copper-induced inhibition of red cell Hx.
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PMID:Metabolic changes in red blood cells in malignant lymphomas. 46 59

Rat brain cytosolic and mitochondrial hexokinase activities were undetectable without added divalent cations. Mg2+ activated cytosolic (K0.5 of Mg2+ = 343 +/- 13 microM) and mitochondrial (K0.5 of Mg2+ = 183 +/- 8 microM) hexokinase in a concentration-related manner. The corresponding values for Mn2+ were 702 +/- 99 and 413 +/- 21 microM respectively. Ca2+, however, activated both forms of hexokinase poorly. In the presence of Mg2+, both Mn2+ and Cu2+ were more potent inhibitors of cytosolic hexokinase than mitochondrial hexokinase, whereas the inhibition of Cd2+ and Ca2+ did not show such selectivity. These results demonstrate that brain mitochondrial and cytosolic hexokinases differ significantly in their responses to divalent cations.
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PMID:Differences in the responses of brain cytosolic and mitochondrial hexokinases to three essential divalent metal ions. 286 Oct 10

The effects of monovalent (Li+, Cs+) divalent (Cu2+, Ca2+, Sr2+, Ba2+, Zn2+, Cd2+, Hg2+, Pb2+, Mn2+, Fe2+, Co2+, Ni2+) and trivalent (Cr3+, Fe3+, Al3+) metals ions on hexokinase activity in rat brain cytosol were compared at 500 microM. The rank order of their potency as inhibitors of brain hexokinase was: Cr3+ (IC50 = 1.3 microM) greater than Hg2+ = Al3+ greater than Cu2+ greater than Pb2+ (IC50 = 80 microM) greater than Fe3+ (IC50 = 250 microM) greater than Cd2+ (IC50 = 540 microM) greater than Zn2+ (IC50 = 560 microM). However, at 500 microM Co2+ slightly stimulated brain hexokinase whereas the other metal ions were without effect. That inhibition of brain glucose metabolism may be an important mechanism in the neurotoxicity of metals is suggested.
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PMID:Differential effects of monovalent, divalent and trivalent metal ions on rat brain hexokinase. 286 Oct 11

Previous studies have shown a marked effect of very high levels of copper on red cell glucose-6-phosphate dehydrogenase and glutathione. When the effect of more nearly physiological levels of copper were studied, red cell hexokinase, phosphofructokinase, phosphoglyceric kinase, pyruvate kinase, and 6-phosphogluconate dehydrogenase were found to be inhibited. Inhibition was observed both when copper was added directly to hemolysates or when hemolysates were prepared from red cells from whole blood which had been incubated with copper and washed. The inhibition of red cell enzymes by copper was completely reversed by the addition of EDTA.
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PMID:The effect of copper on red cell enzyme activities. 425 5

A cation-sensing electrode can be used to monitor enzymatic reactions if their substrates and products differ in the ability to bind the cation. In the first method, the electrode potential vs time curve is recorded. The second, metal-stat method consists of measuring the rate at which substrate must be added to the reaction medium in order to keep the electrode potential at a constant level. These approaches have been used to assay inorganic pyrophosphatase, carboxypeptidase A, and hexokinase with the Mg2+ and Cu2+ ions as the indicators.
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PMID:Use of cation-selective electrodes in enzyme assays. 613 61

1-Formylpyridine monothiosemicarbazonato copper II (CuL+) is readily taken up by red cells and is initially bound to glutathione and hemoglobin. Glutathione was depleted within 5 hr of incubation, presumably by oxidation mediated by CuL+ and O2 with concomitant generation of toxic oxygen species. Cupric ion was slowly transferred from CuL+ to hemoglobin within about 7 hr and hemoglobin was oxidized until the major form prevailing after 10 hr was alpha 2 beta 2+. Little increase in hemolysis due to addition of CuL+ dissolved in the radical scavenger dimethyl sulfoxide was observed with prolonged incubation. Strong inhibition of red cell hexokinase by CuL+ was observed when the enzymes in red cell lysates and hemoglobin-free red cell lysates were examined. CuL+ was also an effective inhibitor of yeast hexokinase. However, the inhibitory effect of CuL+ within the red cells was less pronounced. It is suggested that even though intracellular accumulation of CuL+ creates an oxidizing environment and is potentially capable of inhibiting thiol enzymes such as hexokinase, protective effects are exerted in the red cell by the presence of hemoglobin, of radical scavengers, and of high levels of enzymes that detoxify toxic oxygen species.
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PMID:Effects of 2-formylpyridine monothiosemicarbazonato copper II on red cell components. 622 4

The effects of Cu2+ on glycolysis and several glycolytic enzymes were studied in rat brain extracts in vitro. At concentrations reportedly found in Wilson's disease, Cu2+ significantly inhibited lactate production from glucose or glucose-6-phosphate in rat brain postnuclear supernatant with an IC50 of about 3 microM. Cu2+ also inhibited several glycolytic enzymes. Amongst the latter, Cu2+ was most effective in inhibiting hexokinase (IC50 for Cu2+ = 7 microM), moderately effective in inhibiting pyruvate kinase (IC50 for Cu2+ = 56 microM), but least effective in inhibiting lactate dehydrogenase (IC50 for Cu2+ = 300 microM). These results suggest that inhibition of brain glycolysis may have pathophysiological importance in copper poisoning and in Wilson's disease.
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PMID:Neurotoxic effects of copper: inhibition of glycolysis and glycolytic enzymes. 624 58

Bivalent metal ions, particularly Zn2+ and other members of the first-row transition series, promote irreversible inactivation of yeast hexokinase by Cibacron Blue F3G-A at a site competitive with both ATP and D-glucose. Difference spectroscopy indicates that the protein-dye dissociation constant is decreased from 250 micrometers in the absence of metal ions to less than 100 micrometers in the presence of appropriate concentrations of metal ions, with specificity displayed in the sequence of Zn2+ greater than Cu2+ greater than Ni2+ greater than Mn2+. Quantitative inactivation of yeast hexokinase leads to the incorporation of approx. 1 mol of Cibacron Blue F3G-A/mol of subunit of mol. wt. 51 000 in both the presence and the absence of metal ion. These results suggest the formation of a highly specific ternary complex involving enzyme, dye and metal ion at the active-site region of the enzyme, and correlate well with the known effects of metal ions in promoting the binding of hexokinase to immobilized Cibacron Blue F3G-A.
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PMID:Metal-ion-promoted binding of triazine dyes to proteins. The interaction of Cibacron Blue F3G-A with yeast hexokinase. 675 35

Low concentrations of metal ions, particularly those of the first row transition series such as Zn2+, Co2+, Mn2+, Ni2+, Cu2+, and, to a lesser extent, the group IIA ions, Ca2+ and Mg2+, promotes binding of carboxypeptidase G2, alkaline phosphatase and yeast hexokinase to immobilized Procion Red H-8BN, Procion Yellow H-A and Cibacron Blue F3G-A respectively. The binding of ovalbumin to immobilized Cibacron Blue F3G-A and Procion Orange MX-G is selectively enhanced in the presence of AI3+. With ovalbumin and alkaline phosphatase, the effect is almost totally specific for both the metal ion and dye, whereas with carboxypeptidase G2 and hexokinase, metal ions such as Co2+, Ni2+, Mn2+, Cu2+, Ca2+ and Mg2+ also promote binding to varying degrees. Almost all other monovalent and trivalent metal ions appear to be ineffective. Metal ion-bound enzymes can subsequently be eluted with appropriate chelating agents of the amine, aminocarboxylate or substituted pyridine classes.
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PMID:Metal ion-promoted binding of proteins to immobilized triazine dye affinity adsorbents. 689 1

Two patients with Wilson disease who presented with severe hemolytic anemia are described. One was noted to have unusually high serum copper levels (369 micrograms/100 ml). A review of similar such patients in the literature suggests that, rather than having a low serum copper, patients with hemolysis accompanying Wilson disease have very high serum copper levels. For this reason, in vitro studies of the toxic effects of copper on erythrocytes were undertaken. It was found that, although copper does not have a major direct inhibitory effect on glycolytic enzymes such as hexokinase, the metal does inhibit hexokinase as a consequence of its interaction with oxyhemoglobin. However, such inhibition does not appear to be a major factor in copper-induced hemolysis. On the other hand, the addition of the lipid antioxidant butylated hydroxyanisole (BHA) suppresses hemolysis in copper-treated cells. These experiments suggest that the primary toxic effect of copper is mediated through its oxidant actions on membrane phospholipids rather than through its potential inhibitory effects on intracellular enzymes.
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PMID:Hemolytic anemia in Wilson disease: clinical findings and biochemical mechanisms. 723 65


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