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)

Matched pairs of isogeneic hybrid cells, in which one member of the pair was malignant and the other not, were used to examine the linkage between malignancy and functional alterations in hexose transport. The kinetic parameters of uptake of 2-deoxy-D-glucose were measured in a range of such hybrids, both human and murine. Some other malignant cell lines were also examined and were compared with non-tumorigenic derivatives of tumour cells selected by exposure to the lectin, wheat-germ agglutinin. In every case, malignancy, as defined by the ability of cells to grow progressively in vivo, was found to be linked to a decrease in the Michaelis constant of hexose uptake. Independent measurement of the transport and phosphorylation reactions involved in hexose uptake revealed that this decrease was determined by the membrane transport system. The difference in Michaelis constant between malignant and non-malignant cells was observed with 3-O-methylglucose, a hexose that is transported into the cell but not further metabolized. The activity of hexokinase in cell homogenates was higher than the level that would be required to cope with transport and showed no correlation with tumorigenicity. Measurement of the uptake of D-glucose itself, by a rapid filtration centrifugation method, gave results similar to those obtained with 2-deoxy-D-glucose.
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PMID:Kinetic parameters of hexose transport in hybrids between malignant and nonmalignant cells. 668 24

The isozyme patterns and activities of six enzymes were determined in surgical biopsy samples of lung tumors and non-neoplastic pulmonary areas. Fetal lungs were also examined. No tissue differences were found in the isozyme pattern of hexokinase or alkaline phosphatase; small differences in pyruvate kinase isozyme proportions were observed. The tumors exhibited significant deviations with respect to the lactate dehydrogenase (LDH) and malate dehydrogenase (MDH) isozyme patterns. Despite the diversity of cell types, the proportions of the M-subunit of LDH in each tumor and that of the mitochondrial isozyme of MDH in all but one tumor were higher than in control samples from the same lung. In contrast, the normal fetal lung showed a higher LDH-H proportion than did adult lung and a mature MDH isozyme pattern. The alpha-glycerophosphate dehydrogenase and adenylate kinase activities of the tumors were about one-tenth and one-fourth, respectively, of those of nonneoplastic adult lung. These lower activities (evident also in normal fetal lung) were accompanied by 3- to 5-fold increases in the LDH, MDH, pyruvate kinase, and hexokinase activities of the tumors; fetal lungs had lesser increases (2- to 3-fold) for the first 3 enzymes. The common features of tumors with different cell types and histological grade identified here point to several enzymes the quantitation or isozyme analysis of which may be of practical use in distinguishing cancerous from nonneoplastic human lung samples. A combination of different indicators, such as opposite changes in LDH and alpha-glycerophosphate dehydrogenase activity, coupled with elevated proportions of LDH-M, may be used to diagnose neoplasia most reliably.
Cancer Res 1984 Mar
PMID:Enzyme activities and isozyme patterns in human lung tumors. 669 92

Proliferation of in vitro grown Ehrlich ascites tumor cells is completely inhibited by 0.2-0.4 mM methylglyoxal and 1-2 mM glucosone or galactosone without severely affecting viability (dye exclusion test); no phase-specific arrest of cell growth is observed. Incorporation of [14C] thymidine into the acid-insoluble fraction of the cells decreases within a few minutes to less than 50% of that in controls in the presence of 0.4 mM methylglyoxal, and 2 mM glucosone or galactosone causes a comparable inhibition of DNA synthesis after 2 h or 4 h, respectively. The action of 0.4 mM methylglyoxal inhibits incorporation of [14C] leucine within a few minutes by more than 70%, while 2 mM glucosone and galactosone are significantly less effective (50%-60% inhibition after 12 h). While methylglyoxal and galactosone do not severely affect lactate production of the cells, 2 mM glucosone reduces glycolysis by 60%-70%; ATP/ADP ratios did not fall below 3.5 in the presence of the inhibitors (controls 4-6). It is suggested that the reaction potentialities of the oxaldehyde function of the inhibitors play an important role in their growth-inhibitory activity, besides exerting a specific effect on hexokinase (glucosone) and UTP-trapping activity.
J Cancer Res Clin Oncol 1984
PMID:A comparative study on proliferation, macromolecular synthesis and energy metabolism of in vitro-grown Ehrlich ascites tumor cells in the presence of glucosone, galactosone and methylglyoxal. 673 8

Subcellular distribution of hexokinase (HK) isoenzymes in 22 human breast cancers (21 primary cancers and 1 axillary metastatic growth) and 7 non-pathological human mammary gland tissue samples was studied with starch gel electrophoresis on isolated cell fractions obtained by differential centrifugation. Fractions used were cytosol, mitochondria and microsomes. A comparison of two methods for detecting HK activity was made, yielding different results regarding HK II and HK III. A method based on the ability of NADPH to fluoresce in UV gave a constant pattern of HK isoenzymes. In non-pathological breast tissue, only HK I was seen, i.e. in the cytosol and the microsomal fractions. HK I was also seen in all fractions of the cancers, but another more anodal band of HK I, as well as HK II and HK III, consistently appeared in the cytosol fractions. The more commonly used staining technique with tetrazolium dye revealed HK II in 45% and HK III in 50% of the samples. The pattern of HK isoenzymes in the cancers was the same irrespective of estrogen and progesterone cytosolic receptor contents and the histology of the tumors. The fluorescence method is, therefore, much more sensitive than the tetrazolium technique for detecting HK activity after electrophoresis and could explain difference in results obtained by various laboratories.
Int J Cancer 1984 Jul 15
PMID:Isoenzyme pattern and subcellular localization of hexokinases in human breast cancer and nonpathological breast tissue. 674 20

Enzymes in the histologically normal liver of hosts of mammary carcinomas were examined for their responsiveness to endocrine and dietary modulations. Treatments with the developmental stimuli of alanine aminotransferase (glucocorticoids) and of pyruvate kinase (thyroid hormone) which had no effect in control adult rats raised the levels of these enzymes in the tumor-bearing rats. The latter also showed a greater percentage of increase in malic enzyme upon thyroid hormone administration than did control animals. The tumor-induced increase in hexokinase remained unaltered by the various dietary treatments; enzymes at subnormal levels were raised (glucokinase, malic enzymes, and pyruvate kinase) or further decreased (alanine aminotransferase and ornithine aminotransferase) by excessive carbohydrate intake in immature and adult experimental rats. The normal upsurge of glucokinase and malic enzyme upon weaning to the standard solid diet (from the relatively low-carbohydrate-containing milk) was prevented by cancerous growth in the organism. Similarly, the standard diet, which reversed within 2 days the partial loss of these enzymes in normal adult rats fasted for 48 hr, had no restorative effect on the essentially complete loss of the glucokinase and the very low malic enzyme activity in the fasted tumor bearers. The results suggest that failure in the dietary adaptations of hepatic enzymes as well as diminutions of their basal levels contributes to the clinically observed abnormalities in the glucose metabolism of cancer subjects.
Cancer Res 1983 Apr
PMID:Hormonal and dietary regulation of hepatic enzymes in tumor-bearing rats. 683 4

In response to extrahepatic neoplasms, ornithine aminotransferase, malic enzyme, alanine aminotransferase and glucokinase activity of the 'uninvolved' liver is diminished and that of hexokinase is increased. Comparison of rats at various times after the implantation of ascites tumor, mammary carcinoma, fibrosarcoma and Morris hepatomas indicate that the faster the growth rate of tumors, the earlier the onset of these hepatic changes. The results also show that, when the different tumors are the same size, the magnitude of the enzymic deviations in the liver is directly related to characteristic growth rate of the tumor lines. These and previous observations on other host tissues suggest that tumor-doubling time, which is a known factor in metastatic spread and survival, may also be a variable in the production of systemic agents through which neoplasms affect the metabolic state of the cancer host.
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PMID:Effect of tumors with different growth rates on enzymes in host liver. 687 35

The action of Lonidamine [1-(2,4-chlorobenzyl)-1H-indazol-3-carboxylic acid] on respiration and aerobic lactate production of several murine tumor cells and normal differentiated murine cells was investigated. Lonidamine reduced the oxygen consumption in both normal and neoplastic cells. In contrast, it increased the aerobic glycolysis of normal cells but inhibited that of tumor cells. This selective action might be ascribed to the inhibition of mitochondrially bound hexokinase, which is usually absent in normal differentiated cells.
J Natl Cancer Inst 1981 Mar
PMID:Lonidamine, a selective inhibitor of aerobic glycolysis of murine tumor cells. 693 6

Lymphocyte bioenergetics in cancer patients undergoing surgery is largely unexplored. The effect of surgery on total lymphocyte counts and adenosine triphosphate (ATP) production is reported. Lymphocyte ATP was assayed by the coupled enzymatic method using hexokinase and glucose 6-phosphate dehydrogenase and lymphocyte counts were calculated from total leukocyte counts and differential counts. Lymphocyte ATP assay and counts were carried out in 13 patients pre- and postoperatively, and lymphocyte counts were scored in six more patients similarly. In 69% of the patients lymphocyte ATP production was depressed postoperatively, and this condition appeared to be associated with cancer spread and immunosuppressive tumors. Postoperative increase in lymphocyte ATP was observed following hysterectomy, colostomy, and also after blood transfusion. The significance of the findings are discussed. Changes in postoperative lymphocyte counts correlated with lymphocyte ATP in 62% of the cases.
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PMID:Effect of operation on peripheral lymphocyte counts and production of adenosine triphosphate (ATP) in cancer patients. 707 79

GLycolytic enzymes were studied from normal human retinas (both fetal and adult) and from retinoblastomas of eight patients and an established retinoblastoma cell line. No significant differences were found between the enzyme activities in the tissues investigated except for hexokinase and pyruvate kinase, which were significantly decreased in the tumor cells. In fetal retina, five different forms of pyruvate kinase could be detected by electrophoresis (K4, K3M, K2M2, KM3, and M4). In adult retina the K4 isozyme is almost absent, while in retinoblastoma the M4 isozyme is hardly present. In the retinoblastoma cell line, the M4 isozyme is completely absent. Alanine inhibition of pyruvate kinase from the retinoblastoma cell line is more inhibited compared to the pyruvate kinase of fetal retina and retinoblastoma and is even more inhibited compared to adult retina. Electrophoresis of aldolase from adult retina revealed the presence of all potential A-C hybrids (A4, A3C, A2C2, AC3, and C4). Fetal retina, however, is characterized by the predominance of the A type. The same patterns were observed in the retinoblastoma cell line and retinoblastoma. However, in other brain tumors, e.g., gliomas of adults, a five-membered A-C hybrid set is found. Electrophoresis of hexokinase from normal fetal and adult retina revealed the predominance of hexokinase type I; retinoblastoma and retinoblastoma cell line are both characterized by the presence of considerable amounts of hexokinase type II. The isozyme shifts in retinoblastoma result in an enzyme pattern identical to that of fetal retina except for the presence of hexokinase type II.
Cancer Res 1982 Oct
PMID:Characterization of some glycolytic enzymes from human retina and retinoblastoma. 710 15

Rat liver cytoplasm (postnuclear supernatant) has a low aerobic glycolytic rate in the presence of added glucose, ATP, ADP, Pi, and NAD+, whereas cytoplasm from Ehrlich ascites tumor cells exhibit a high aerobic glycolytic rate which is typical of rapidly proliferating tumor cells. Tumor mitochondria, unlike liver mitochondria, contain bound hexokinase which constitutes about 70% of the total cellular hexokinase activity. The high aerobic glycolytic rate of Ehrlich tumor cytoplasm is reduced markedly if the mitochondria are removed and can be restored almost completely upon addition of the hexokinase-containing tumor mitochondria to tumor cytosol (postmitochondrial supernatant). Addition of tumor mitochondria to liver cytosol can enhance its glycolytic rate to levels approaching those of tumor cytoplasm, whereas added liver mitochondria are without effect on the already low glycolytic rate of liver cytosol. Addition of tumor mitochondria to tumor cytosol increases its glycolytic rate to the level of tumor cytoplasm, as mentioned above, but liver mitochondria added to tumor cytosol actually depress its glycolytic rate to the level of liver cytosol. The stimulatory effect of tumor mitochondria on liver cytosol can be ascribed to its associated hexokinase activity since hexokinase specifically removed from mitochondria of tumor cells can also enhance the glycolytic rate of liver cytosol. The depressing effect of added liver mitochondria on tumor cytosol glycolysis suggests that liver mitochondria can compete more effectively than tumor mitochondria for a common intermediate and/or cofactor. Examination of 12 different tumor cell lines revealed that only those which reached maximum size in 1 month or less, and which have elevated glycolytic activities, had detectable mitochondrially associated hexokinase activity. The studies reported here describe resolution and reconstitution of tumor cytoplasm, supplementation of cytosol with intact mitochondria or mitochondrial hexokinase, and a survey of mitochondrial hexokinase content in various tumors, and provide strong evidence for the view (Bustamante, E., and Pedersen, P. L. (1977) Proc. Natl. Acad. Sci. U. S. A. 74, 3735-3739) that a form of hexokinase with a propensity for mitochondrial binding plays a key role in the high aerobic glycolysis of cancer cells.
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PMID:Energy metabolism of tumor cells. Requirement for a form of hexokinase with a propensity for mitochondrial binding. 726 78


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