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 concentrations of ten or 12 enzymes involved in the metabolism of DNA, collagen, amino acids, or glucose have been determined in variants of human intestinal and pulmonary tissues. In comparison to nonneoplastic adult colon, normal fetal colon had elevated concentrations of thymidine kinase, peptidyl proline hydroxylase, phosphoserine phosphatase, ornithine transcarbamylase, gamma-glutamyl transpeptidase, and ornithine aminotransferase. Raised activities of the first five of these enzymes, and of hexokinase, glucose-6-phosphate dehydrogenase, and pyrroline-5-carboxylate reductase distinguishes neoplastic from nonneoplastic sections of adult colon. Study of a wide range of pulmonary specimens permitted comparisons of different types of tumors, and revealed some subtle differences between lungs of noncancer patients and nonneoplastic portions of host lungs. The concentrations of eight previously identified enzymic indicators were less in moderately or well differentiated than in poorly differentiated pulmonary adenocarcinomas. The latter differed from epidermoid carcinomas (also poorly differentiated) by containing lower concentrations of thymidine kinase (both soluble and particulate) and hexokinase.
Cancer 1980 Nov 01
PMID:Enzyme activities in human fetal and neoplastic tissues. 625 48

The purpose of the present enzymic and histologic analysis of pulmonary samples from 39 subjects was to discern a common, meaningful pattern which may underlie the biochemical heterogeneity of lung neoplasms. The distribution among the different tumors of thymidine kinase, uridine kinase, phosphoserine phosphatase, hexokinase and adenylate kinase was found to correlate with each other. By averaging their standardized units (normal lung = 0) an enzymic index of neoplasticity was calculated for each tumor and used (in increasing order) to rank all 39. The index, showing a significant positive correlation with mitotic frequency, encompassed a continuous 100-fold range. Poorly differentiated carcinomas ranked high while neoplasms with better differentiation and prognosis placed in the lower half of the range. The results indicate that enzymes showing coordinated variations over a broad spectrum of tumors could contribute objective criteria to the rating of any individual tumor against a continuous, quantitative scale of neoplasticity.
Cancer 1982 Feb 01
PMID:Enzyme pathology and the histologic categorization of human lung tumors: the continuum of quantitative biochemical indices of neoplasticity. 627 48

In this study pyruvate kinase, hexokinase and aldolase are investigated in two types of embryonal tumors, neuroblastomas and medulloblastomas; the results are compared with similar studies in gliomas. The activities of hexokinase and pyruvate kinase are significantly decreased in neuroblastomas. In neuroblastoma and medulloblastoma all five forms of pyruvate kinase (K4, K3M, K2M2, KM3 and M4) are present. In contrast, the gliomas investigated are characterized by the presence of mainly K4 and a little K3M. In neuroblastomas, medulloblastomas and gliomas, hexokinase type I is present; in addition, hexokinase type II is present in two medulloblastomas. Aldolase A is the predominant isozyme in all tumors investigated; this is in contrast with normal nervous tissue. It can be concluded that the isozyme characteristics especially of pyruvate kinase from neuroblastomas and medulloblastomas are comparable with similar findings in retinoblastoma; these findings support the hypothesis that these three tumors have a common embryonic origin.
Eur J Cancer Clin Oncol 1984 Feb
PMID:Glycolytic enzymes from human neuroectodermal tumors of childhood. 632 86

The experimental and theoretical bases for the use of Lonidamine in cancer therapy are reviewed and discussed. In murine tumors Lonidamine has a narrow spectrum of antitumor effects. It lacks the characteristic properties of antiproliferative drugs, as well as other important pharmacological actions, with the exception of antispermatogenic and embryotoxic effects which are closely related to the antitumor ones. Lonidamine appears not to affect the cell division processes. Available data instead show that it specifically affects the condensed or oxidized mitochondrion; since tumor cells have a mitochondrially bound hexokinase, both respiration and glycolysis are decreased. There is some evidence that hyperthermia, X rays and some chemotherapeutic agents, when used in combination with Lonidamine, increase the response of tumor cells or systems to this drug.
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PMID:Lonidamine, a new approach to cancer therapy. 637 44

Lymph-node cells of (AKR X C3H) F1 leukaemic mice showed a considerable increase of glycolytic activity and O2 consumption. The glycolytic enzymes phosphofructokinase, pyruvate kinase, aldolase and lactic acid dehydrogenase showed increased activities in leukaemic conditions. Studies on permeabilized leukaemic and normal lymph-node cells, and assays on partially purified phosphofructokinase and pyruvate kinase enzymes, revealed that the enhanced glycolysis of the tumour cells was due to the predominance of glycolytic isoenzymes relatively insensitive to the natural metabolic inhibitors. The glycolytic enzyme hexokinase showed decreased activity in leukaemic conditions, owing to a subcellular translocation of its bulk from the cytosol to the mitochondrial fraction. Association of hexokinase with the mitochondria accounted for an ATPase-like stimulatory action on cell respiration which can explain the increased O2 uptake of leukaemic cells.
Br J Cancer 1981 Jun
PMID:Regulation of glycolysis and oxygen consumption in lymph-node cells of normal and leukaemic mice. 645 31

The efflux of adenine nucleotides was studied in mitochondria isolated from normal rat liver, host livers, and the tumors from four Morris hepatoma lines of varying growth rates. [3H]Adenosine diphosphate (ADP) or [3H]adenosine triphosphate (ATP) was preloaded to the energized mitochondria, and the initial rates of exchange with unlabeled extramitochondrial nucleotides were measured with the carboxyatractyloside stop method. Results indicate that the Vmax values of ATP efflux in mitochondria from fast and intermediately growing tumors (hepatoma cell lines 7777, 7800, and 5123D) are significantly smaller than that of host or normal liver mitochondria, while in slow growing tumor (line 16) the Vmax is not different. On the other hand, for ADP efflux, the opposite (namely, higher in tumor than in host) is observed in the mitochondria of fast growing tumors. Preincubation with the divalent cation ionophore A23187 and calcium chelator ethyleneglycolbis(beta-aminoethyl ether)-N,N'-tetraacetic acid increases the efflux of both ATP and ADP (to a lesser extent) in these tumor mitochondria, indicating that the extraordinarily high concentrations of calcium form complexes with adenine nucleotides (particularly ATP) and thus lower the effective concentrations of free nucleotides for translocation. Together with previously published results (R. L. Barbour and S. H. P. Chan, Cancer Res., 43: 1511-1517, 1983) on lower nucleotide uptake rates in these tumor mitochondria, we propose that the lower ATP efflux and higher ADP efflux rates may cause a futile cycle of ADP transport across the mitochondrial membrane which may contribute to high rates of aerobic glycolysis (by stimulating key glycolytic enzymes such as hexokinase and phosphofructokinase) observed in these fast and intermediately growing tumors.
Cancer Res 1984 Oct
PMID:Efflux of adenine nucleotides in mitochondria from rat tumor cells of varying growth rates. 646 6

Hypoxic cells in solid tumors are known to be resistant to radiation, and may also be resistant to some anti-cancer drugs. Biochemical properties of hypoxic cells, such as their dependence on anaerobic glycolysis leading to production of lactate and low pH might have potential for inhibition by drugs with selective activity against hypoxic cells. Such drugs might improve the Therapeutic Index when used with radiation or some conventional anti-cancer drugs. Preliminary studies have shown that the combination of hypoxia and low pH (pH 6.5-6.0) was cytotoxic to Chinese Hamster Ovary (CHO) cells incubated in vitro for up to 6 hours, although neither factor alone reduced plating efficiency. Lonidamine, an inhibitor of mitochondrially-bound hexokinase and lactate transport, was cytotoxic to CHO cells at low pH, but had no effect at physiological pH under aerobic or hypoxic conditions. Lonidamine has also been tested for in vivo effects against three murine tumors: the KHT fibrosarcoma, 16/C mammary carcinoma and the Lewis Lung Tumor. The drug was tested either alone, or with radiation or Adriamycin to kill aerobic cells, and/or with glucose and insulin to lower intra-tumor pH. No major therapeutic effects have been demonstrated.
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PMID:The effect of the drug lonidamine on Chinese hamster ovary cells in vitro and on experimental tumors. 648 Apr 46

The activities of six different enzymes were compared in 29 normal, 34 dysplastic, and 80 cancerous (both primary and metastatic) human breast tissues; in MCF-7 cells; and in primary rat mammary tumors. Benign lesions generally showed enzyme activities similar to those of normal breast tissues. Malignant tumors had significantly increased activities of lactate dehydrogenase (LDH), malate dehydrogenase (MDH), fructose-bisphosphate aldolase, hexokinase (HK), pyruvate kinase (PK), and creatine kinase. Enzyme activity in the malignant tumor was always higher than that in apparently normal or fibrocystic tissue from the same patient. Enzyme activities did not correlate with the levels of estrogen and progesterone receptors. LDH, MDH, and HK were elevated to a similar extent in all the tissues examined. Conversely, PK was elevated to a much greater extent in cancerous tissues, particularly in MCF-7 cells. The elevated activities of these enzymes may have diagnostic potential, especially when tumor tissue and apparently normal tissue from the same patient are compared.
J Natl Cancer Inst 1984 Feb
PMID:Enzyme activities in normal, dysplastic, and cancerous human breast tissues. 658 10

The activity, isoenzyme distribution and compartmentation of hexokinase (ADP: D-hexose-6-phosphotransferase, EC 2.7.1.1) were compared in slowly growing, well-differentiated medullary thyroid carcinoma (DMTC) and rapidly proliferating anaplastic thyroid carcinoma (AMTC) in the rat. Individual isoenzymes from either soluble or particulate fractions after solubilization were obtained by fast protein liquid chromatography and were kinetically analyzed either in soluble form or after (re)binding to rat liver mitochondria. These studies were undertaken to test the hypothesis that the growth rate of tumors is correlated with the activity of mitochondrial-bound hexokinase in our tumor system. In contradiction to this hypothesis, we found no difference in either enzyme activity or compartmentation of both kinds of tumors. The major part of enzyme activity was soluble (73 and 78% in DMTC and AMTC respectively). In addition, no major differences were observed in the kinetic properties of the individual isoenzymes of both tumors. Only soluble type II hexokinase from AMTC had a slightly decreased apparent Km for glucose. There appeared to be some differences in isoenzyme composition: both tumors contained type I and type II hexokinase in the soluble as well as in the particulate fractions. However, the proportion was shifted in favor of type II hexokinase in the soluble fraction of AMTC. Additional findings of this study were the following: the affinity of type II hexokinase to both substrates glucose and MgATP2- was significantly less compared to type I hexokinase. However, the inhibition constant for glucose-1,6-diphosphate of both isoenzymes was exactly the same. The bound form of both isoenzymes had the same substrate affinities as the soluble form but was considerably less inhibited by glucose-1,6-diphosphate. In the latter respect, type I and type II hexokinase behaved in the same way.
Eur J Cancer Clin Oncol 1984 Jul
PMID:Hexokinase isoenzymes from anaplastic and differentiated medullary thyroid carcinoma in the rat. 661 Dec 65

A study of hexokinase isozymic pattern and age dependence of the enzyme was carried out on erythrocytes of 4 patients with adenocarcinoma of the gastrointestinal tract. On the basis of our results, we think that the increase in hexokinase activity previously reported and the increase in both subtypes (Ia and Ib) of the enzyme herein described are not due to a mean younger red cell population caused by secondary anemia, which is frequently present in cancer patients.
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PMID:Relationship between erythrocyte hexokinase in cancer patients and red cell age. 667 38


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