Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.1 (hexokinase)
5,274 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The R3230AC mammary adenocarcinoma was not dependent on insulin; tumor growth was equal to or greater in diabetic rats than in intact animals. However, tumor growth was reduced when daily doses of insulin were administered. Treatment with estrogen inhibited growth of the R3230AC carcinoma, either in diabetic rats or in intact animals simultaneously treated with insulin. The effects of insulin plus estrogen treatment appeared to be additive in causing inhibition of tumor growth. Tumors from diabetic rats showed few metabolic alterations as reflected by little or no changes in the activities of selected glycolytic enzymes, pyruvate kinase, phosphofructokinase, and hexokinase, nor any striking changes in the activities of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase, representing the pentose phosphate pathway. A modest reduction in the ratio of utilization of (1-14C)glucose: (6-14C)glucose was seen in vitro by tumors from diabetic rats. It was concluded that insulin, along with estrogen and prolactin, should be considered as a hormonal factor that influences growth of this automonous, hormone-responsive adenocarcinoma.
Cancer Res 1975 Mar
PMID:Influence of insulin on estrogen-induced responses in the r3230ac mammary carcinoma. 12 68

The activity of the following enzymes was studied in normal, precancerous, and malignant biopsies from the human cervix uteri: hexokinase (HK), phosphofructokinase (PFK), pyruvate-kinase (PK), lactate dehydrogenase (LDH), and glucose-6-phosphate dehydrogenase (G-6-PDH). In precancerous conditions, i.e., dysplasia and carcinoma in situ without any signs of invasive carcinoma, only PK showed moderate but significant activity increases. A rise in enzyme activity in biopsies histologically classified as carcinoma in situ was found to signal the presence of invasive carcinoma in other parts of the cervix. In invasive carcinomas of the cervix, all the enzymes studied showed a two- to four-fold increase (p less than 0.01) as compared to the normal cervix. The present study failed to reveal significant differences between enzyme activities in biopsies from patients in Stage I, II, and III; no correlation could be established between enzyme activity and prognosis.
Cancer 1975 Feb
PMID:The glycolytic enzyme activity of the human cervix uteri. 16 34

Avian and mammalian fibroblast cultures transformed by type C sarcoma viruses show a dramatic enhancement of the rate of hexose transport at the beginning of transformation which is quantitatively and qualitatively different from that seen by variation in culture conditions of nontransformed control cells. The identification of this change as being a transport alteration independent of total glucose metabolism has been shown by use of nonmetabolizable analogues, 2-deoxyglucose, 3-O-methylglucose, and L-glucose. Increased transport rates were not dependent on levels of hexokinase activity. Transport studies of 3-O-methylglucose confirmed these conclusions and further revealed an additional altered nature of hexose transport after transformation by sarcoma virus. 3-O-methylglucose was not only transported more rapidly in the transformed cells than in the parental nontransformed cells, but the sugar "infiltrated" into the transformed cells despite the inhibitory effect of cytochalasin B. This was not seen with control cells. The sarcoma cells were also able to transport L-glucose in contrast to lack of uptake by nontransformed cells. Under conditions in which cell toxicity was not a factor, 2-deoxyglucose and several other sugars present in culture media inhibited transformation by sarcoma viruses. These same sugars reduced the incidence of sarcomas produced by virus in vivo when administered daily to test animals. The transport changes also correlate well with the transformed state as found by other laboratories using temperature-sensitive mutants and revertant cell lines. Collectively these data suggest that manipulation of transport systems may prove useful for control of certain malignancies.
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PMID:Hexose transport in sarcoma virus transformed cells. 16 30

Considerable thymidine kinase and pyrroline-5-carboxylate reductase activities were found in the plasma of rats bearing a transplanted lymphoma; neither activity was detected in plasma of hosts carrying hepatic, renal, mammary, or submaxillary gland tumors. All host livers exhibited signs of biochemical immaturity as indicated by the appropriate increases or decreases in the concentrations of the nine enzymes measured. The extent and time schedule of the changes in host liver varied with the enzyme and with the tumor that caused them. The hepatic concentrations of ornithine aminotransferase, arginase, pyrroline-5-carboxylate reductase, and glucokinase (all diminished), and of peptidyl proline hydroxylase and hexokinase (increased) were sensitive indicators of tumor growth in general. The concentration of ornithine aminotransferase decreased before the tumors became palpable. At more advanced stages, the high hepatic thymidine kinase activity distinguished the presence of hepatoma and lymphoma from those of all other equally fast-growing tumors. However, only in lymphoma-bearing rats did a fivefold elevation of hepatic thymidine kinase occur as early as 4 days after implantation. Additional observations on the lymphoma itself, on blood cells, and on the involuting thymus of normal rats indicate that the striking systemic effects of this tumor cannot be explained by a release of enzymes from the thymus or by the increased number of lymphoma cells present in blood or liver.
Cancer Res 1977 Jan
PMID:The effect of lymphoma and other neoplasms on hepatic and plasma enzymes of the host rat. 18 34

The concentrations of 16 to 21 enzymes, representing various metabolic pathways, have been determined in human adult, fetal, and neoplastic lung. At midgestation, 12 enzymes (among them, several that metabolize amino acids) were above their adult values while 3 other enzymes were still at low concentrations. These signs of biochemical immaturity are contrasted and compared with those in fetal human liver and rat lung. The enzymic composition of the 11 human pulmonary tumors studied resembled that of the normal fetal lungs closely; the same 12 enzymes were elevated and the same 2 were decreased (compared to nonneoplastic adult lung) in both. The characteristic abnormality in the overall pattern of enzymes, in the concentrations of individual ones, and in the quality of pyrroline-5-carboxylate reductase was clearly evident in both primary and metastatic tumors. The mean concentrations of 10 enzymes in the tumors were significantly different (higher or lower) from those in the control lungs (p less than 0.001 to less than 0.05). The best markers of neoplasticity were thymidine kinase, peptidyl proline hydroxylase, phosphoserine phosphatase, hexokinase, and pyrroline-5-carboxylate reductase. The results demonstrate that quantification of a small battery of enzymes, none of them tissue specific, can distinguish adult human lung from its neoplasms.
Cancer Res 1977 Mar
PMID:The undifferentiated enzymic composition of human fetal lung and pulmonary tumors. 18 17

Experimental data suggest that contrary to the findings obtained for normal and regenerating liver of mouse, the greater part of hexokinase (HK) in transplantable hepatomas is firmly bound to mitochondrial membranes. It is shown that the ratio of the bound HK activity (HKbound) to that of total HK activity (HKtotal) diminishes with a hepatoma growth. Malignization of hepatocytes also leads to a sharp decrease in the cytochrome oxidase (CO) octivity. Though the data obtained are well-correlated with the Warburg hypothesis, there is no direct correlation between the malignancy of hepatomas evaluated by their growth rates, and the biochemical parameters of the tumours studied. On the basis of fundamental principles of Warburg's, it is proposed to evaluate energy metabolism of hepatomas by the activity and subcellular distribution patterns of HK as well as be the activity of CO, according to the expression: [(HKtotal)2//HKbound-CO+HKbound-CO]. It is demonstrated that there exists a certain linear dependence between the integral characteristics of hepatoma energetics and their growth rates.
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PMID:[Biochemical characteristics determining the rates of tumour growth in the organism]. 19 Nov 4

The total activity of hexokinase (HK) and HK isoenzymic spectrum of the normal liver and slowly groming hepatoma 49 did not show any essential differences. However, the HK total activity and the relative and absolute contents of isoenzyme HK-3 were increased in hepatomas 61 and especially in the rapidly growing hepatoma 22-a. The glucokinase activity decreases in the hepatiomas 49 and 61 and disappears in the rapidly growing hepatoma 22-a. The glucose content in hepatoma 49 was slightly lower than in the normal liver, whereas in other hepatoma no traces of glucose could be detected. At low glucose concentration in the medium (0,1 mM), i.e. under conditions simulating those characteristic of tumors in vivo, the predominant form of HK in all hepatomas studied was found to be HK-3. In the liver of hepatoma-bearing mice some shifts in the value of total HK activity and its isoenzymic spectrum, reminding one of those found in hepatomas themselves, were observed. Unequal deviations in the total HK activity and its isoenzymic spectrum in hepatomas with different degrees of malignancy indicate that these characteristics are secondary rather than primary events depending on tumour progression.
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PMID:[Some characteristics of isoenzymic spectrum of hexokinase and glucose levels in hepatomas and liver of the host]. 19 29

In hepatomas of various malignancy contrary to normal and regenerating liver tissue a considerable part of hexokinase (HK) activity was bound with mitochondria. The HK activity, estimated in nuclei, microsomes and apparently in cytoplasma membranes, was due to contamination with mitochondrial fraction. High specific activity of HK in mitochondria of tumors might be responsible for the increased glycolysis, when these organelle preparations were added to the soluble fraction of cells. The HK of tumors was extracted from the preparations by alternative pathways. Reversible binding of some part of the enzyme with mitochondria was regulated by concentration of metabolites (ATP and G6P) similarly to the bound HK from normal tissues (brain, retina). At the same time the other part of unregulated HK activity (isozyme I only) was found in hepatomas to be intercalated into lipoprotein membranes; it was not controlled by metabolites.
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PMID:[Subcellular distribution of hexokinase in hepatoma and its electrophoretic properties]. 19 17

An ultramicrochemical technique has been adapted to the evolution of enzyme profiles within individual human mammary tumors. Tandem observation of adjacent stained and lyophilized sections permitted dissection of microgram quantities of freeze-dried material within confirmed regions of malignancy. Enzymes frequently monitored to examine glycolytic, respiratory, and metastatic capacity were microanalyzed successfully: lactic dehydrogenase (LDH), phosphoglucose isomerase (PGI), malate dehydrogenase (MDH), acid phosphatase (AP), aldolase (ALD), glucose-6-phosphate dehydrogenase (G6PDH), pyruvate kinase (PK), alpha-glycerophosphate dehydrogenase (alpha-GOPDH), hexokinase (HK), and phosphofructokinase (PRK). All enzyme activities were higher in infiltrating ductal carcinomas than in fibroadenomas. Extracts of tumor cells mixed in varying proportions with brain or muscle extracts of rat evidenced no modification of expected activity. The technical adaptation described provided a sensitive methodology to resolve problems of relication, profile analysis, sample quantity, and selectivity within heterogeneous tissues.
Cancer 1978 May
PMID:Application of a microchemical technique to the elucidation of enzyme activity profiles within single human mammary tumors. 20 41

The activity of hexokinase was studied in several normal and malignant human tissues. The enzyme activity in tumors was significantly higher. Isoenzyme studies on normal gastric mucosa and stomach cancer extracts showed that malignancy is accompanied by a "simplification" of the hexokinase isoenzyme pattern due to "deletion" of the slowest isoenzyme. Preparative polyacrylamide gel electrophoreis was used to isolate hexokinase isoenzymes from normal and malignant tissues. Tumor hexokinase isoenzymes displayed an increased affinity to glucose when compared to the corresponding normal prototypes (Km/glucose, 10(-6) M and 10(-5) M, respectively; Km = Michaelis constant). The molecular weights, subunit composition, and peptide patterns were identical for corresponding isoenzyme pairs from normal and tumor tissues.
J Natl Cancer Inst 1978 Jul
PMID:Physicochemical properties and isoenzyme composition of hexokinase from normal and malignant human tissues. 27 35


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