Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Properties of aryl hydrocarbon hydroxylase in the microsomes were compared between Morris hepatoma 5123D and the host liver from rats bearing this tumor. Requirement of NADPH for the assay of the enzyme activity was observed, compared to that of NADH, and also the additive effect of NADH on the requirement of NADPH was found in the tumor and liver. Curve of pH optimum of the enzyme activity in tumor and liver differed between the rats treated with corn oil and those with 3-methylcholanthrene, indicating a slight shift of the peak value to alkaline pH in the latter. The same values of the apparent Km for NADPH and NADH were shown for the enzyme from the liver and tumor even 24 hr after the treatment with 3-methylcholanthrene, but a difference in the apparent Km for benzo[a]pyrene was demonstrated between the tumor and the host liver, showing 3.6 approximately 6.6 muM in the former and 9.1 approximately 20 muM in the latter. By the addition of 7,8- or 5,6-benzoflavone to the assay medium for the tumor, the induced enzyme was inhibited noncompetitively, and the constitutive enzyme was enhanced, as demonstrated in the host liver. As observed in the induced enzyme in both tissues, cyclohexene oxide and 1,1,1-trichloropropane oxide slightly increased the activity of the constitutive enzyme in the tumor, in contrast to its inhibition in the host liver.
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PMID:Properties of aryl hydrocarbon hydroxylase in microsomes of Morris hepatoma 5123D and the host liver. 0 50

The activities of microsomal stearoyl-CoA desaturation, NADH-cytochrome b5 reductase, NADH-cytochrome c reductase, and the content of cytochrome b5 were similar in livers of normal and host rats. On the other hand, stearoyl-CoA desaturation activity was absent in Novikoff hepatoma. The activities of NADH-cytochrome b5 and NADH-cytochrome c reductases in the hepatoma microsomes were 4.8% and 2.2%, respectively, of those in normal liver. Furthermore, in hepatoma microsomes, cytochrome b5 was absent. An active stearoyl-CoA desaturation was reconstituted only on addition of both cytochrome b5 and the terminal desaturase enzyme to the hepatoma microsomes. These results indicated that a complete absence of cytochrome b5 and terminal desaturase is responsible for the lack of stearoyl-CoA desaturation in Novikoff hepatoma microsomes.
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PMID:Stearoyl-coenzyme A desaturase activity in Novikoff hepatoma. 3 26

1. Ethanol metabolism in slices or homogenates of transplantable hepatocellular carcinoma HC-252 (HC-252) was 50 to 60% of the rate found in host liver slices or homogenates when they were expressed per gram of tissue wet weight and 70 to 80% of the liver when the rates were expressed per milligram of tissue protein. At 10 mM ethanol, the activities of alcohol dehydrogenase in tumor and liver supernatants were comparable. 2. Tumor microsomes did not oxidize ethanol in the presence of a NADPH-generating system, indicating the absence of the microsomal ethanol-oxidizing system and catalase-mediated peroxidation of ethanol. The HC-252 microsomes were contaminated with catalase, and acetaldehyde production occurred in the presence of a H2O2-generating system (xanthine oxidase). The virtual absence of ethanol oxidation and drug metabolism (aminopyrine demethylase and aniline hydroxylase) in HC-252 microsomes may be due to the low activities of NADPH-cytochrome c reductase, NADPH oxidase, and NADPH-dependent oxygen uptake. 3. Microsomal oxidation of ethanol was present in Morris hepatoma 5123C, a well-differentiated tumor of intermediate growth rate, while activity was negligible in microsomes from Morris hepatoma 7288CTC, a less differentiated tumor. Microsomal NADPH oxidase was present in the well differentiated tumor 5123C but was lacking in the less differentiated tumor 7288CTC. Several microsomal, mitochondrial, and cytosolic properties of HC-252 are similar to those of Morris hepatoma 7288CTC but differ from those of the more differentiated 5123C tumor and normal liver. 4. The content of mitochondrial protein in HC-252 was only 25% that of liver, and oxygen consumption per gram of tumor was only 28% that of the liver. When corrected for the mitochondrial protein content, oxygen uptake in tumor HC-252 and liver homogenates was comparable. Isolated tumor and liver mitochondria displayed comparable State 4 and 3 rates of oxygen consumption with succinate and glutamate as substrates. The activities of the reconstituted malate-aspartate and alpha-glycerophosphate shuttles were only slightly lower in isolated HC-252 mitochondria compared to liver mitochondria, when shuttles were reconstituted with purified enzymes. 5. Antimycin inhibited alcohol metabolism,and pyruvate stimulated alcohol metabolism, much less in tumor slices than in liver slices, suggesting the presence of an augmented mitochondria-independent, cytosolic mechanism for oxidizing reducing equivalents in the tumor. These factors suggest that oxidation of NADH is the limiting factor in ethanol metabolism. Whereas, in the liver mitochondrial reoxidation is predominant, in HC-252, cytosolic reoxidation of NADH also plays a major role.
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PMID:Ethanol metabolism by a transplantable hepatocellular carcinoma. Role of microsomes and mitochondria. 13 37

The activity of the malate-aspartate shuttle for the reoxidation of cytoplasmic reduced nicotinamide adenine dinucleotide (NADH) by mitochondria was assessed in six lines of rodent ascites tumor cells (two strains of Ehrlich ascites carcinoma, Krebs II carcinoma, Novikoff hepatoma, AS-30D hepatoma, and L1210 mouse leukemia). All the tumor cells examined showed mitochondrial reoxidation of cytoplasmic NADH, as evidenced by the accumulation of pyruvate when the cells were incubated aerobically with L-lactate. Reoxidation of cytoplasmic NADH thus generated was completely inhibited by the transaminase inhibitor aminooxyacetate. The involvement of the respiratory chain in the reoxidation of cytoplasmic NADH was demonstrated by the action of cyanide, rotenone, and antimycin A, which strongly inhibited the formation of pyruvate from added L-lactate. Compounds that inhibit the carrier-mediated entry of malate into mitochondria, such as butylmalonate, benzenetricarboxylate, and iodobenzylmalonate, also inhibited the accumulation of pyruvate from added L-lactate by the tumor cells. The maximal rate of the malate-aspartate shuttle was established by addtion of arsenite to inhibit the mitochondrial oxidation of the pyruvate formed from added lactate. The capacity of the various tumor lines for the reoxidation of cytoplasmic NADH via the malate-aspartate shuttle approaches 20% of the total respiratory rate of the cells and thus appears to be sufficient to account for the mitochondrial reoxidation of that fraction of glycolytic NADH not reoxidized by pyruvate and lactate dehydrognenase in the cytoplasm.
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PMID:Occurrence of the malate-aspartate shuttle in various tumor types. 17 6

Ascites hepatoma cells grown in Wistar rats were incubated anaerobically in the absence of glucose or in the presence of both glucose and D(+)glucosamine, or monoiodoacetate, or NADH, which interfered with glycolysis at different steps and with different mechanisms: Under all these conditions the incorporation of amino acids into the proteins of hepatoma cells was severely reduced without any clear relationship to the degree of inhibition of glycolysis. The postmitochondrial supernatants showed defective incorporation only when obtained from cells incubated in the absence of glucose or in the presence of monolodoacetate; inhibition of glycolysis by glucosamine and NADH did not seem to affect the subcellular basis for protein synthesis. When present, the defect of the cell sap (monoiodoacetate and absence of glucose) and to disaggregation and reduced functional capacity of the polysomes (absence of glucose). The results suggested that the effects of the inhibition of glycolysis on protein synthesis and on the integrity of the protein-synthesizing machinery--which were primarily due to the depletion of the energy stores--might have been modified by the particular mechanism of action of the inhibitor and by the way low levels of ATP were reached in the cell.
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PMID:Inhibition of glycolysis and interference with protein synthesis in hepatoma cells. 19 Apr 11

The activity of delta9 desaturase was determined in the microsomal fraction of normal mouse liver and hepatoma SS1K in the presence of the 105,000 x g supernatant. Neither hepatic nor hepatoma soluble fractions were able to modify the low desaturating capacity. Two enzymes from the microsomal electron transport chain associated with delta9 desaturase, namely NADH-cytochrom b5 reductase and NADH-cytochrom C reductase were also measured. The results indicate that the low delta9 desaturase activity in hepatoma SS1K could be related to the reduced amount of desaturase.
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PMID:delta9 Desaturase activity in normal mouse liver and hepatoma SS1K. 20 43

Serum glutamic oxaloacetic transaminase (GOT), mitochondrial GOT (GOTm), glutamic-pyruvic transaminase (GPT) and glutamate dehydrogenase activities were determined in 43 healthy controls and in 280 cases of liver diseases. A simplified column chromatographic method coupled with UV assay was employed for separation of GOTm. The activity was measured by following decrease in abosrbance of NADH at 340 nm. The lowest activity of GOTm determined with a coefficient of variation below 10% was 6 mIU/ml. High GOTm activities were found in acute hepatitis (acute stage), subacute hepatitis and primary biliary cirrhosis and were generally associated with high total GOT (GOTt) activities. The activity ratio of GOTm/GOTt varied depending on the stage and severity of liver diseases. The GOTm/GOTt ratio was decreased in acute, fulminant and subacute hepatitides. No significant reduction in the ratio was found in bile duct obstruction, alcoholic liver injury or metastatic liver cancer. Although relatively high GOTm/GOTt ratios were found in some patients with severe hepatic injury, they had no definite association with poor prognosis. These results indicate that the marked elevation in GOTt over GPT in advanced chronic hepatitis, liver cirrhosis and primary hepatoma was mainly due to preferential leakage of cytoplasmic GOT (GOTs).
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PMID:The mechanism of the release of hepatic enzymes in various liver diseases. 1. Alterations in cytoplasmic and mitochondrial enzyme activities in serum. 22 31

The prerequisit of reduction for activation of Mitomycin-C and unstability of its reduced form suggested investigation of the possible formation of free radicals (semiquinone forms) of a series of quinone-containing anticancer chemicals in vitro. The ability of rat-liver microsomes to initiate sulfite oxidation in the presence of NADPH was markedly enhanced by the addition of these chemicals. This strongly suggests that these chemicals participated in the process in the form of reactive free radicals. The reaction was specific for NADPH. Carbazilquinone was unique among others in that NADH can replace NADPH and its higher ability to initiate sulfite oxidation. Microsomes from Ehrlich ascites and AH-109A hepatoma cells were also effective, though to a lesser extent than those from rat liver on a protein basis. Generation of free radicals, though their biological significance is not clear at present, may be deemed an inherent chemical property of these chemicals.
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PMID:Generation of free radicals of quinone group-containing anti-cancer chemicals in NADPH-microsome system as evidenced by initiation of sulfite oxidation. 23 81

The activity of NADPH- and NADH-dependent erythrocyte glutathione reductase was determined in rats with Morris 5123 hepatoma at different stages of tumor development (10, 20, 30 and 40 days after transplantation). During the early stage of tumor growth the activity of glutathione reductase with either of these coenzymes was increased. In the late stage of the disease the activity of NADPH-dependent glutathione reductase fell below control values. The obtained results are discussed in the light of previous observations on the effects of this neoplasm on the metabolism of erythrocytes.
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PMID:[Glutathione reductase activity in erythrocytes of rats with transplantable Morris 5123 hepatoma]. 73 12

1. The reoxidation of cytosolic NADH was studied in a line of human hepatoma cells (HuH13) whose mitochondria preferentially utilized glutamine for ATP formation. 2. The tumor cells showed mitochondrial reoxidation of NADH, as evidenced by the accumulation of pyruvate, when incubated aerobically with L-lactate. The involvement of the respiratory chain was demonstrated by the addition of specific inhibitors. 3. Glutamine oxidation proceeded in the tumor mitochondria exclusively via a pathway involving transamination. Malate stimulated aspartate production from glutamine. 4. When the tumor cells were cultured in Eagle's medium with aminooxyacetate or in the absence of glutamine, a marked reduction in the cellular NAD/NADH ratio was observed. 5. These results indicate that the malate-aspartate shuttle was functioning in the tumor cells.
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PMID:Oxidation of cytosolic NADH by the malate-aspartate shuttle in HuH13 human hepatoma cells. 131 Feb 90


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