Mevalonate-mediated suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase function in alpha-toxin-perforated cells
| Autor: | Maria D. Giron, Christopher Havel, John A. Watson |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
Squalene
Staphylococcus aureus 7-Dehydrocholesterol reductase Cell Membrane Permeability Coenzyme A Mevalonic Acid CHO Cells Mevalonic acid Biology Reductase Models Biological Pyrophosphate chemistry.chemical_compound Cricetinae Animals chemistry.chemical_classification Multidisciplinary Dose-Response Relationship Drug Chinese hamster ovary cell Sterol Clone Cells Kinetics Enzyme chemistry Biochemistry Type C Phospholipases Hydroxymethylglutaryl CoA Reductases Hydroxymethylglutaryl-CoA Reductase Inhibitors Signal Transduction Research Article |
| Zdroj: | Proceedings of the National Academy of Sciences. 91:6398-6402 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | The regulation of mevalonic acid synthesis requires both nonsterol isopentenoid and sterol regulatory signal molecules. A primary target of this multivalent control process is the enzyme which catalyzes mevalonate synthesis: 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (EC 1.1.1.34). In this report Staphylococcus aureus alpha-toxin perforated Chinese hamster ovary cells were used to facilitate the identification of isopentenoidogenic reactions and metabolites required for mevalonate-mediated loss of HMG-CoA reductase activity. alpha-Toxin-perforated cells retained the capacity to decrease, upon demand, HMG-CoA reductase activity and protein in response to mevalonate or isopentenoid pyrophosphate esters. Also, it was deduced with highly specific metabolic inhibitors, that conversion of farnesyl 1-diphosphate to squalene was required for mevalonate-mediated suppression of reductase activity. Since squalene (2 microM) did not downregulate reductase activity, pre-squalene pyrophosphate or a derivative, or polyprenyl-1-pyrophosphate-generated inorganic pyrophosphate, or a combination of these metabolites are proposed as candidate regulatory nonsterol isopentenoid signal molecules. |
| Databáze: | OpenAIRE |
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