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| Content Provider | Springer Nature Link |
|---|---|
| Author | Pan, Shujia J. Combs, Alan B. |
| Copyright Year | 2003 |
| Abstract | This work was designed to test whether phosphofructokinase is a target for emetine action on the heart. The effects of 37, μM emetine on the activities of phosphofructokinase and hexokinase were measured in homogenates from perfused hearts. The action of increasing concentrations of emetine was determined in nonperfused heart homogenates. The effect of 37 μM emetine or control solutions on the concentration of fructose-6-phosphate and fructose-1,6-phosphate was measured. The effect of 37 μM emetine or control perfusion on the utilization of fructose-6-phosphate by phosphofructokinase in centrifugation supernatants of homogenates and in reconstituted 27,000g pellets was measured. Double-reciprocal plots of fructose-6-phosphate concentrations vs phosphofructokinase activities were plotted. Emetine decreased phosphofructokinase activity in homogenates from both perfused and nonperfused hearts. Emetine did not inhibit cardiac hexokinase activity. In homogenates from nonperfused hearts, the maximal inhibition with high concentrations of emetine was approx 50%. Emetine perfusion caused a simultaneous increase in the phosphofructokinase substrate fructose-6-phosphate and a decrease in the phosphofructokinase product fructose-1,6-bisphosphate. Phosphofructokinase and, consequently, glycolytic flux appear to be subcellular targets for emetine in the heart. Homogenate centrifugation studies indicate that emetine acts on bound rather than unbound phosphofructokinase. The inhibition may be uncompetitive in nature. |
| Starting Page | 311 |
| Ending Page | 318 |
| Page Count | 8 |
| File Format | |
| ISSN | 15307905 |
| Journal | Cardiovascular Toxicology |
| Volume Number | 3 |
| Issue Number | 4 |
| e-ISSN | 15590259 |
| Language | English |
| Publisher | Humana Press |
| Publisher Date | 2003-01-01 |
| Publisher Place | Totowa |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Emetine cardiotoxicity glycolysis phosphofructokinase cardiac perfusion Pharmacology/Toxicology Cardiology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Molecular Biology Toxicology Cardiology and Cardiovascular Medicine |
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