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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The outer mitochondrial membrane contains a pore structure which is composed of a 30,000 Da protein, porin. The pore has an internal diameter of 2 nm and exhibits a molecular-sieving exclusion limit between 3000 and 6000 Da. These pores, therefore, provide the exit/entrance port for metabolites moving between mitochondria and the cytosol. Hexokinase binds to porin on the outer surface of mitochondria. The location of hexokinase has evoked a number of theories in which bound hexokinase is given a central role in regulating glycolysis, and, perhaps, the metabolic communication between oxidative and glycolytic metabolism. This is of particular importance in rapidly growing tumor cells in which the aerobic production of lactate and hexokinase activity are highly induced. In the present paper, we summarize the suggested roles of the outer membrane and bound hexokinase in regulation glycolysis of tumor cells. Experiments attempting to elucidate the role of hexokinase binding in the regulation of tumor cell metabolism are presented.
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PMID:The role of the mitochondrial outer membrane in energy metabolism of tumor cells. 242 23

Ehrlich ascites tumor cells were permeabilized using low concentrations of digitonin, 8 micrograms/10(6) cells. Permeabilization was monitored by the assay of lactate dehydrogenase released into the incubation medium and of hexokinase partially bound to mitochondria. Integrity of the cellular organelles was unaffected as determined by assay of the mitochondrial enzyme glutamate dehydrogenase. Cells were stained with rhodamine 123 as a mitochondrial specific dye and propidium iodide/mithramycin as DNA specific dyes. The green fluorescence of bound rhodamine 123 versus red fluorescence of DNA in individual cells was analysed by dual parameter flow cytometry. Incubation of cells with inhibitors of mitochondrial energy metabolism, such as, potassium cyanide and carbonyl cyanide m-chlorophenylhydrazone abolished binding of rhodamine 123. Flow cytometric data allowed a correlation between cell position in the mitotic cycle with total mitochondrial activity. In addition, comparison of the characteristics of propidium iodide and ethidium bromide staining further elucidated the molecular basis of the staining with the positively-charged fluorescent dye rhodamine 123.
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PMID:Simultaneous analysis of mitochondrial activity and DNA content in Ehrlich ascites tumor cells by dual parameter flow cytometry. 248 81

Significance of the binding of hexokinase to mitochondria was examined with respect to stabilization of the enzyme by the binding. Stability during the incubation of the mitochondria-bound forms of hexokinases I and II, both prepared from Ehrlich-Lettre ascites hyperdiploid tumor cells (ELD cells), were compared with that of the corresponding free forms. During the incubation at pH 7.4 and 37 degrees C up to 60 min, hexokinase activities decreased gradually, and the decrease in the activity of the free form was much more marked than that of the bound form for both hexokinases. Hexokinase II was much less stable than I, and the activity of the free form of the former was almost lost by the incubation for 15 min. But, more than a half of the original activity of hexokinase II was retained even after 60 min of the incubation when the enzyme was bound to mitochondria. Addition of 50 mM glucose increased the stability of hexokinase II, but the stabilizing effect was less marked for hexokinase I. On the other hand, addition of 28 mg/ml of bovine serum albumin markedly stabilized hexokinase I to almost the same extent as was observed with mitochondria. On the contrary, the serum albumin had little stabilizing effect on hexokinase II. These findings indicate that the binding to mitochondria stabilizes the hexokinases of ELD cells, though the stability is different by nature between hexokinases I and II.
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PMID:Stabilization of hexokinases I and II of ELD cells by binding to mitochondria. 271 12

Mannosephosphate isomerase (MPI) showed a higher activity than hexokinase (HKM) in its ability to phosphorylate mannose in the spleen, thymus, brain, liver, striated muscles, kidneys, and testes from BALB/c mice. This led to a HKM/MPI ratio of less than 1 in all the organs and tissues mentioned. In contrast, Ehrlich ascites tumor cells obtained from the peritoneum of BALB/c mice had low MPI activity (half of the HKM activity and, therefore, a ratio of 2). Mannose, which is nontoxic to nontumor cells at a concentration of 0.1 M, induced marked in vitro mortality of the tumor cells. Incubation of Ehrlich ascites tumor cells with mannose resulted in a high accumulation of mannose-6-phosphate and a marked depletion of ATP which did not appear when the cells were incubated with glucose. These facts may explain the selective mortality caused by mannose in the tumor cells studied.
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PMID:Mannose toxicity in Ehrlich ascites tumor cells. 277 33

Activities of key carbohydrate-metabolizing enzymes in biopsied human tissues of hepatocellular carcinoma and related conditions were determined by established methods. Among the enzymes analyzed, fetal-type liver enzymes (low-Km hexokinase, glucose 6-phosphate dehydrogenase, and pyruvate kinase-M2) showed increased activities, and adult-type liver enzymes [glucose 6-phosphatase, fructose 1,6-bisphosphatase, high-Km hexokinase (or glucokinase), and pyruvate kinase-L] showed decreased activities, resulting in undifferentiated enzyme patterns not only in fetal livers and hepatocellular carcinomas but also in livers of acute and chronic hepatitis and liver cirrhosis with or without tumors. Hepatocellular carcinomas showed a general tendency of having greater enzyme deviations than hepatitic and cirrhotic livers. The extent of the enzyme deviation in hepatocellular carcinomas varied considerably from one enzyme to another for each tumor tissue as compared with that in the benign liver diseases. Thus, the phenotypic heterogeneity was important for discriminating between the neoplastic and inflammatory changes in differentiation markers. The enzyme patterns of tumors and their corresponding host cirrhotic livers were unrelated, suggesting that the cirrhotic liver has a significance as preneoplastic state only in terms of having a high incidence of evolving hepatocellular carcinoma.
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PMID:Profiles of carbohydrate-metabolizing enzymes in human hepatocellular carcinomas and preneoplastic livers. 282 76

A study on the enzyme activity of glucose metabolism in the lymphocytes of patients with solid malignant tumors is reported. The results have shown a 30% mean increase of the hexokinase (HK) activity in patients with solid malignant tumors as compared to the mean value observed in a group of healthy subjects. A relationship between level of HK increase and stage of tumor was also observed. The other examined enzyme activities, phosphofructokinase (PFK), pyruvate-kinase (PK), phosphoglycerate-kinase (PGK), phosphoglucoisomerase (PGI), glyceraldehyde-phosphate dehydrogenase (GAPD) glucose-6-phosphate dehydrogenase (G-6PD), 6-phosphogluconate dehydrogenase (6-PGD) and enolase did not show significant changes. It is concluded that even though the use of HK as tumor marker cannot be hypothesized at the present time, a significant relation between an increased activity of this enzyme and presence of the tumor is unquestionable. Therefore, this biochemical effect induced away from the neoplastic tissue deserves further study.
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PMID:Solid tumors and enzyme activity in human lymphocytes. 283 4

It was investigated whether the well-known transplantable insulinoma of the hamster (the Kirkman tumor) contains glucokinase and if so, what its kinetic characteristics are, and whether its cellular levels might be regulated in a manner typical for islet tissue. The supernatant of tumor homogenates contained a low-affinity component (Km 9.7 mmol/L) of glucose phosphorylating activity, apparently glucokinase. Partially purified insulinoma glucokinase exhibited similar kinetic characteristics to liver glucokinase (Km for glucose 5.0 and 5.3 mmol/L, half-maximal saturation 6.9 and 6.3 mmol/L, Hill coefficient 1.63 and 1.62, Ki for mannoheptulose 0.9 and 0.6 mmol/L in hamster insulinoma glucokinase and hamster liver glucokinase, respectively). Insulinoma glucokinase activity was not affected by the age of the tumor. Tumor-bearing hamsters without further treatment stayed normoglycemic (172 +/- 9.5 mg/dL) for the duration of the experiment. Fasting caused hypoglycemia (49 +/- 5.0 mg/dL), and pretreatment with streptozotocin prior to tumor transplantation caused hyperglycemia (393 +/- 20.6 mg/dL) in the tumor-bearing hamsters. Blood glucose levels of the host hamsters did not affect the content of the insulinoma glucokinase (83 +/- 3.5 mU/g in hypoglycemic group, 88 +/- 9.0 mU/g in hyperglycemic group, and 86 +/- 3.5 mU/g in normoglycemic group). Thus, biosynthesis and degradation of insulinoma glucokinase does not seem to be regulated by glucose as found to be true for islet glucokinase. Since glucokinase is constitutively present, the stable transplantable Kirkman tumor could serve as a useful model for studying the pancreatic B-cell glycolysis system which is characterized by the presence of both hexokinase and glucokinase.
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PMID:Characteristics of glucokinase of the Kirkman insulinoma. 283 31

The effect of Adriamycin on mitochondria of the rat heart, liver, and Ehrlich ascites tumor mitochondria has been evaluated. The results may be summarized as follows: Adriamycin reduces both ADP- and FCCP-stimulated respiration, inhibits oxidative phosphorylation, decreases mitochondrial ATP-ase activity, and affects the redox state of respiratory carriers. These alterations are common to all types of mitochondria tested with almost similar patterns. However, the severe cardiotoxicity of the drug cannot be ascribed only to an effect on mitochondrial energy-yielding processes. The addition of hexokinase to phosphorylating heart mitochondria does not increase the sensitivity of succinate oxidation to Adriamycin. Experiments to determine the site of action were not able to detect a specific point of attack. It is conceivable, therefore, that the modifications induced by Adriamycin on the functional parameters of mitochondria may be ascribed to alterations of the physical state of some components of the inner mitochondrial membrane, e.g., lipids, which regulate the kinetic properties of the membrane-associated enzymes.
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PMID:Effect of adriamycin on electron transport in rat heart, liver, and tumor mitochondria. 287 39

The effect of exogenously added adenylate cyclase from Bordetella pertussis (strain 114) has been investigated in Y-1 mouse adrenal tumor, chinese hamster ovary (CHO) and several other cells. A partially purified adenylate cyclase was found not to enter cells but, nevertheless, produced large amounts of cAMP in the medium. We could show that this resulted from release of ATP (and not larger molecules). The ATP released by the cells could be (1) directly measured and was replenished after each change of medium; (2) was reciprocally related to the cAMP produced; and (3) was competed for by ATPases present in added serum or by hexokinase and, less effectively, by exoenzymes on the cell surface. The extent of ATP leakage varied widely between different cell lines, being marked in CHO and Y-1 adrenal cells but negligible in transformed lymphocyte lines. The uncertainty of the origin of cAMP found in media of cultured cells requires separate analysis of cell and medium cAMP and an assessment of ATP leakage.
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PMID:Extracellular cAMP formation from host cell ATP by Bordetella pertussis adenylate cyclase. 290 Jun 55

The potent tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) induced a rapid increase in glycolysis in rat thymocytes. The increase in the glycolytic flux was also reflected by elevated fructose 1,6-diphosphate levels. TPA treatment did not result in an increase of hexokinase, phosphofructokinase or pyruvate kinase when measured in cell homogenates. It is suggested that the early increase in glycolysis in TPA treated lymphocytes may result from TPA-mediated increase in glucose transport.
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PMID:12-O-Tetradecanoylphorbol-13-acetate enhances glycolysis in rat thymocytes. 293 56


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