Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies were carried out to determine the effects of preincubation of 4-methyl-5-amino-1-formylisoquinoline thiosemicarbazone (MAIQ) with hepatic microsomes on the ability of MAIQ to inhibit CDP reductase activity in vitro. An aliquot from the 100,000 x g supernatant fraction from this incubation was used in the CDP reductase assay. MAIQ incubated in the absence of microsomes inhibited CDP reductase activity in a dose-dependent manner. At high MAIQ concentration (5 microM) CDP reductase activity was inhibited 95%. When MAIQ (5 microM) was first incubated in the presence of hepatic microsomes and NADPH, CDP reductase activity was inhibited only 30%. This attenuation of MAIQ inhibition was dependent on time of incubation and microsomal protein concentration and showed an obligatory requirement for NADPH or NADH. Significant attenuation was observed at pyridine nucleotide concentrations as low as 0.1 mM. Heat denaturation of microsomal proteins inactivated their ability to attenuate the MAIQ inhibition. Microsomes prepared from Ehrlich tumor cells were ineffective as inactivators of MAIQ. Results of our studies show that hepatic microsomes contain an enzyme(s) which can inactive MAIQ as an inhibitor of CDP reductase.
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PMID:Liver microsomal inactivation of 4-methyl-5-amino-1-formylisoquinoline thiosemicarbazone as an inhibitor of ribonucleotide reductase. 305 1

A simple way of measuring and evaluating lactate dehydrogenase release from lysed tumor cells is described. LDH activity was determined as NADH oxidation or INT reduction over a defined time interval, which was limited by stopping the enzymatic reaction with the inhibitor oxamate. Reaction products were then assayed using a microplate reader. The principle of measuring LDH activity of cellular culture supernatants as a measure of cytotoxicity was successfully applied to a number of murine and human effector-target cell combinations (macrophages, monocytes, NK cells and cytotoxic T cells with P815, A375, K562 and Yac-1 tumor cells) as well as to the determination of TNF activity on L929 cells. Comparison with 51Cr release assays suggests that LDH release assays are an appropriate and possibly preferable means of measuring cellular cytotoxic reactions. This LDH release assay combines the advantages of reliability and simple evaluation characteristic of radioisotope release assays with the convenience of speed and avoidance of radioactivity.
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PMID:A quick and simple method for the quantitation of lactate dehydrogenase release in measurements of cellular cytotoxicity and tumor necrosis factor (TNF) activity. 319 48

A transmembrane ferricyanide reductase activity was assayed in intact Ehrlich ascites tumor cells. Kinetic measurements gave a Km of 0.14 mM and a Vmax of 0.31 mumol/min per 10(6) cells. In short-term batch experiments, this activity was enhanced in the presence of 10 mM lactate, a source of cytosolic NADH. The transmembrane redox activity was accompanied by alkalinization of the cytosol. Both ferricyanide reduction and proton extrusion were diminished in the presence of 0.2 mM amiloride. Several cytotoxic drugs significantly inhibited the ferricyanide reductase activity at concentrations at which they show antineoplastic activity.
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PMID:Transmembrane ferricyanide reductase activity in Ehrlich ascites tumor cells. 320 24

The bifunctional NAD-dependent methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase from ascites tumor cells has very different kinetic properties from the larger NADP-dependent methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase-formyltetrahydrofolate synthetase present in all mammalian cells. The NAD-dependent dehydrogenase is unique in that it requires formation of a magnesium.enzyme complex to allow addition of the first substrate, NAD+. It catalyzes an equilibrium ordered kinetic mechanism that has methylenetetrahydrofolate as the last reactant to add and NADH as the last product released. The NADP-dependent dehydrogenase has the same order of addition of substrates, but NADPH is released prior to methenyltetrahydrofolate. The dehydrogenase-cyclohydrolase activities of both enzymes channel methenyltetrahydropteroylglutamate intermediates with the same efficiency which is unaffected by the number of glutamyl residues in the methylenetetrahydrofolate substrate. However, the cyclohydrolase activity of the bifunctional protein is kinetically independent of its dehydrogenase activity, as supported by its lack of inhibition by NAD+, whereas NADP+ strongly inhibits that of the NADP-dependent enzyme. This difference is further demonstrated by the observation that conversion of formyltetrahydrofolate to methylenetetrahydrofolate in the presence of reduced pyridine nucleotide is catalyzed readily only by the bifunctional enzyme.
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PMID:The activities of the NAD-dependent methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase from ascites tumor cells are kinetically independent. 325 7

The highly active alcohol dehydrogenase (EC 1.1.1.1) in rat hepatic tumor cells (HTC) was purified 120-fold by chromatography on DEAE-Sepharose and AMP-Agarose to yield an enzyme with a specific activity of 88 mumole/min/mg protein, assayed with 1.7 mM NAD+ and 0.55 M ethanol at pH 9 and 30 degrees C. (By comparison, purified, normal rat liver enzyme has an activity of about 1 unit/mg.) Based on its physical and kinetic properties, we conclude that the HTC isozyme is the same as the enzyme from rat stomach and another rat hepatoma (Cederbaum AI, Pietruszko R, Hempel J, Becker FF, and Rubin E (1975) Arch Biochem Biophys 171:348-360). The kinetics of the HTC enzyme are consistent with the Ordered Bi Bi mechanism. The kinetic constants are generally much larger for the HTC enzyme than for the normal rat liver enzyme. The Michaelis constants for ethanol and acetaldehyde (Kb = 1100 mM, Kp = 260 mM) are 1000-fold larger, and the constants for NADH are 10 to 50-fold larger. Although the HTC enzyme has low catalytic efficiency (V/Kb) on ethanol, it has much better activity on longer chain alcohols, but no activity on cyclohexanol. The pH dependence of V/Kb with ethanol is unusual in that it appears to be a linear function of pH, increasing with a slope of 0.56. Thus, the active sites of the liver and HTC enzymes may be different, although the HTC enzyme is inactivated by bromoacetate and bipyridine as is found for the liver enzyme. The HTC (stomach) enzyme may function to oxidize high concentrations of ingested ethanol or longer chain alcohols.
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PMID:Characterization of alcohol dehydrogenase from cultured rat hepatoma (HTC) cells. 361 21

The activity of the malate-aspartate shuttle for the reoxidation of reduced cytosolic nicotinamide adenine dinucleotide (NADH) by mitochondria was studied in a line of human myeloid leukemia cells (K-562). The tumor cells showed mitochondrial reoxidation of cytosolic NADH, as evidenced by the accumulation of pyruvate, when incubated aerobically with L-lactate. The involvement of the respiratory chain in the reoxidation of cytosolic NADH was demonstrated by the action of rotenone, antimycin A, and oligomycin which strongly inhibited the formation of pyruvate from added L-lactate. Moreover, pyruvate production was greatly inhibited by the transaminase inhibitor, aminooxyacetate. Under glycolytic conditions, in the presence of aminooxyacetate, the rate of pyruvate production was also markedly inhibited, the rate of lactate accumulation was stimulated, and at 60 min the cytosolic NADH/nicotinamide adenine dinucleotide (NAD) ratio had increased progressively about 5-fold with respect to untreated cells. The maximal rate of the malate-aspartate shuttle has also been established by addition of arsenite to inhibit mitochondrial oxidation of the pyruvate formed from added L-lactate.
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PMID:Oxidation of reduced cytosolic nicotinamide adenine dinucleotide by the malate-aspartate shuttle in the K-562 human leukemia cell line. 375 5

Experiments are presented showing that specific inhibition of mitochondrial protein synthesis by tetracyclines decreases the activity of the NADH-dehydrogenase complex in liver mitochondria, if rats are treated for long periods with these antibiotics. The corresponding inhibition of this complex in tumor cells (Zajdela hepatoma) and tumor mitochondria (Leydig cell tumor) is even more pronounced. It is concluded that the mitochondrial genetic system is involved in the assembly of the NADH-dehydrogenase complex, most likely by coding for one or more subunits. It is argued that this information, contrary to the situation for cytochrome c oxidase, the cytochrome bc1 complex and ATPsynthase, has been missed in previous experiments employing differential inhibition of mitochondrial protein synthesis, because of the circumstance that the inhibition did not reach the level at which it became rate-limiting.
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PMID:The effect of long-term inhibition of mitochondrial protein synthesis on the oxidation capacity of mitochondria for NADH-linked substrates. 392 42

In a proliferating giant cell tumor of bone the activities of tartrate-resistant acid phosphatase (acPase) and of NADH-tetrazolium reductase were demonstrated by enzyme histochemical methods. Quantitative microphotometry made it possible to determine the relative enzyme activities per given volume unit in the cytoplasm of giant cells of several sizes. The activity of tartrate-resistant acid phosphatase increases with increasing cell size, whereas the activity of tetrazolium reductase will decrease in proportion. This coincidence of high acPase activity and low tetrazolium reductase activity in larger giant cells is interpreted as an expression of degenerative change.
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PMID:Microphotometric quantitation of enzyme activities in giant cell tumor of bone. A case study. 398 18

The function of glycerophosphate and malate-aspartate shuttles during glucose metabolism in two strains of Ehrlich ascites tumor cells was evaluated by several experimental approaches. The activities of the enzymes involved in these shuttle systems were assayed in the cytosolic and mitochondrial compartments after cell fractionation by the digitonin method. The glycerophosphate shuttle can be ruled out because of the lack of relevant enzymatic activities, and the failure of glucose to increase rotenone-inhibited respiration. Analysis of glycolytic flux in the presence of aminooxyacetate indicates that the activity of malate-aspartate shuttle may be very low. Balance studies of glucose uptake and lactate production suggest the existence of other pathways for the reoxidation of cytosolic NADH, which are acetyl-CoA dependent. Estimation of citrate synthase and ATP citrate lyase, in addition to the observed high activity of malate dehydrogenase, suggests a malate-citrate shuttle.
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PMID:The function of redox shuttles during aerobic glycolysis in two strains of Ehrlich ascites tumor cells. 400 10

Electron microscope studies were carried out with the adrenocortical carcinoma 494 and normal adrenal cortex tissue. The mitochondria of the tumor cells showed marked differences when compared with mitochondria from fasciculata cells of the normal adrenal cortex. These differences were primarily related to mitochondrial number and crista structure. Corticosterone production in isolated tumor cells was extremely low and neither ACTH nor dibutyryl cyclic AMP had any stimulatory effect. Normal adrenal cells showed at least a tenfold increase under identical conditions. In the presence of corticosteroid precursors the amount of corticosterone produced by the tumor cells was much less than that produced by normal cells. The results indicate a reduced capacity for 11beta-hydroxylation in the tumor mitochondria and a possible reduced capacity for biosynthetic steps before the 11beta-hydroxylation reaction. Glycolysis in isolated tumor cells was also lower than in normal cells. Isolated tumor mitochondria oxidized succinate normally with a good degree of coupling with phosphorylation. However, unlike normal adrenal mitochondria, the tumor mitochondria showed little or no oxygen uptake with other Krebs cycle substrates. These data suggest that the tumor mitochondria may be lacking in the flavoprotein dehydrogenases responsible for the oxidation of NADH and NADPH, although other components of the respiratory chain may be intact.
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PMID:Ultrastructure, steroidogenic potential, and energy metabolism of the Snell adrenocortical carcinoma 494. A comparison with normal adrenocortical tissue. 436 5


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