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)

Brusatol, a quassinoid with potent antineoplastic activity against P-388 lymphocytic leukemia cell proliferation, significantly inhibited P-388 cell hexokinase, phosphofructokinase, malic dehydrogenase, and succinic dehydrogenase. Mitochondrial oxidative phosphorylation, basal, and adenosine diphosphate-stimulated respiration, utilizing succinate and alpha-ketoglutarate as the substrate, was suppressed significantly by in vivo treatment with brusatol. However, brusatol treatment had no effect on liver oxidative phosphorylation. Brusatol greatly increased P-388 cyclic AMP levels but had no effect on liver cyclic nucleotides. Similar inhibitory effects on P-388 cell oxidative phosphorylation were found in vitro with brusatol, bruceoside A, and bruceantin. Brusatol had no effect on adenosine triphosphatase activity or on uncoupling of oxidative phosphorylation. Rather, brusatol appeared to increase the concentration of reduced mitochondrial electron-transport cofactors, thereby blocking aerobic respiration. A proposed mechanism of action is discussed.
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PMID:Antitumor agents. XXXV: Effects of brusatol, bruceoside A, and bruceantin on P-388 lymphocytic leukemia cell respiration. 22 89

In tumoral cells derived from the insulin-producing rat cell line RINm5F, both low- and high-Km glucose-phosphorylating enzymic activities were present. The hexokinase-like enzyme was inhibited by glucose 6-phosphate and displayed a greater affinity for but lower maximal velocity with alpha-D-glucose than beta-D-glucose. A comparable anomeric behavior of hexokinase was observed in breast cancer (MCF-7) and lymphocytic leukemia (P388) cells. Thus, the anomeric specificity of hexokinase in tumoral cells was not different from that recently characterized in normal mammalian cells.
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PMID:Anomeric specificity of hexokinase in rat, human, and murine tumor cells. 390 82

3-Chloromethylthiochromone-1,1-dioxide was observed to be a potent inhibitor of Ehrlich ascites carcinoma growth and a moderate inhibitor of P-388 lymphocytic leukemia growth at 10 mg/kg/day. Preliminary in vitro studies showed that the agents significantly inhibited RNA and DNA synthesis in Ehrlich ascites cells. In vivo studies after dosing on Days 6, 7, and 8 demonstrated the same reductions in nucleic acid synthesis and a moderate reduction in protein synthesis. The primary site of nucleic acid synthesis, which was blocked by 3-chloromethylthiochromone, was at orotidine monophosphate decarboxylase in the primidine pathway. Other enzymes, in anaerobic and aerobic glycolysis, which were blocked include hexokinase, phosphofructokinase, succinic and alpha-ketoglutarate dehydrogenases, as well as States 3 and 4 of oxidative phosphorylation.
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PMID:Effects of 3-chloromethylthiochromone-1,1-dioxide on nucleic acid, protein, and aerobic and anaerobic metabolism of Ehrlich ascites tumor cells. 712 85