Genomes and Genes
Summary: A dihydroxy monocarboxylic acid and precursor in the biosynthetic pathway known as the mevalonate pathway, which produces terpenes and steroids that are vital for diverse cellular functions.
- Pontillo A, Paoluzzi E, Crovella S. The inhibition of mevalonate pathway induces upregulation of NALP3 expression: new insight in the pathogenesis of mevalonate kinase deficiency. Eur J Hum Genet. 2010;18:844-7 pubmed publisher..This is the first time that the involvement of the inflammasome complexes was shown in MKD pathogenesis. ..
- Clendening J, Pandyra A, Boutros P, El Ghamrasni S, Khosravi F, Trentin G, et al. Dysregulation of the mevalonate pathway promotes transformation. Proc Natl Acad Sci U S A. 2010;107:15051-6 pubmed publisher..Taken together, our results suggest that HMGCR is a candidate metabolic oncogene and provide a molecular rationale for further exploring the statin family of HMGCR inhibitors as anticancer agents...
- Musso A, Zocchi M, Poggi A. Relevance of the mevalonate biosynthetic pathway in the regulation of bone marrow mesenchymal stromal cell-mediated effects on T-cell proliferation and B-cell survival. Haematologica. 2011;96:16-23 pubmed publisher..b>Mevalonic acid could revert morphological, phenotypic and functional effects of fluvastatin...
- Simkin A, Guirimand G, Papon N, Courdavault V, Thabet I, Ginis O, et al. Peroxisomal localisation of the final steps of the mevalonic acid pathway in planta. Planta. 2011;234:903-14 pubmed publisherIn plants, the mevalonic acid (MVA) pathway provides precursors for the formation of triterpenes, sesquiterpenes, phytosterols and primary metabolites important for cell integrity...
- Miziorko H. Enzymes of the mevalonate pathway of isoprenoid biosynthesis. Arch Biochem Biophys. 2011;505:131-43 pubmed publisher..The conversion of mevalonic acid to isopentenyl 5-diphosphate involves three ATP-dependent phosphorylation reactions...
- Tsuruta H, Paddon C, Eng D, Lenihan J, Horning T, Anthony L, et al. High-level production of amorpha-4,11-diene, a precursor of the antimalarial agent artemisinin, in Escherichia coli. PLoS ONE. 2009;4:e4489 pubmed publisher..Production of >25 g/L amorpha-4,11-diene by fermentation followed by chemical conversion to artemisinin may allow for development of a process to provide an alternative source of artemisinin to be incorporated into ACTs. ..
- Bentinger M, Tekle M, Dallner G. Coenzyme Q--biosynthesis and functions. Biochem Biophys Res Commun. 2010;396:74-9 pubmed publisher..One approach for this purpose is administration of epoxidated all-trans polyisoprenoids, which enhance both CoQ biosynthesis and levels in experimental systems. ..
- Schaafsma D, Dueck G, Ghavami S, Kroeker A, Mutawe M, Hauff K, et al. The mevalonate cascade as a target to suppress extracellular matrix synthesis by human airway smooth muscle. Am J Respir Cell Mol Biol. 2011;44:394-403 pubmed publisher..These findings reveal mechanisms related to evidence for the positive impact of statins on pulmonary health. ..
- Fildes J, Shaw S, Williams S, Yonan N. Potential immunologic effects of statins in cancer following transplantation. Cancer Immunol Immunother. 2009;58:461-7 pubmed publisher..This hypothetical review attempts to delineate the mode of action of statins in terms of pro/anti-carcinogenic mechanisms, while considering graft rejection and the presence of immunosuppression. ..
- Asadollahi M, Maury J, Schalk M, Clark A, Nielsen J. Enhancement of farnesyl diphosphate pool as direct precursor of sesquiterpenes through metabolic engineering of the mevalonate pathway in Saccharomyces cerevisiae. Biotechnol Bioeng. 2010;106:86-96 pubmed publisher..This could be explained by a toxicity effect of cubebol, possibly resulting in higher transcription levels for the genes under control of MET3 promoter, which could lead to accumulation of squalene and ergosterol. ..
- Freed Pastor W, Mizuno H, Zhao X, Langerød A, Moon S, Rodríguez Barrueco R, et al. Mutant p53 disrupts mammary tissue architecture via the mevalonate pathway. Cell. 2012;148:244-58 pubmed publisher..Finally, p53 mutation correlates with highly expressed sterol biosynthesis genes in human breast tumors. These findings implicate the mevalonate pathway as a therapeutic target for tumors bearing mutations in p53. ..
- Fukunaga M, Nunomura S, Nishida S, Endo K, Gon Y, Hashimoto S, et al. Mast cell death induced by 24(S),25-epoxycholesterol. Exp Cell Res. 2010;316:3272-81 pubmed publisher..Our present findings confer new insights into the roles of lipid metabolism during oxysterol-mediated mast cell apoptosis. ..
- Niknejad N, Morley M, Dimitroulakos J. Activation of the integrated stress response regulates lovastatin-induced apoptosis. J Biol Chem. 2007;282:29748-56 pubmed..Therefore, lovastatin, by targeting mevalonate synthesis, is a potent inducer of the ISR through a novel and as yet unrecognized mechanism. ..
- Zeki A, Franzi L, Last J, Kenyon N. Simvastatin inhibits airway hyperreactivity: implications for the mevalonate pathway and beyond. Am J Respir Crit Care Med. 2009;180:731-40 pubmed publisher..Simvastatin and similar agents that modulate the mevalonate pathway may prove to be treatments for inflammatory airway diseases, such as asthma. ..
- Kotamraju S, Williams C, Willams C, Kalyanaraman B. Statin-induced breast cancer cell death: role of inducible nitric oxide and arginase-dependent pathways. Cancer Res. 2007;67:7386-94 pubmed..NO biosynthesis by NOS. We conclude that iNOS-mediated (.)NO is responsible in part for the proapoptotic, tumoricidal, and antiproliferative effects of statins in MCF-7 cells. ..
- Wang C, Yoon S, Shah A, Chung Y, Kim J, Choi E, et al. Farnesol production from Escherichia coli by harnessing the exogenous mevalonate pathway. Biotechnol Bioeng. 2010;107:421-9 pubmed publisher..Introduction of the exogenous MVA pathway enabled the dramatic production of FOH by E. coli while no detectable FOH production was observed in the endogenous MEP pathway-only control...
- Zhou Y, Gao W, Rong Q, Jin G, Chu H, Liu W, et al. Modular pathway engineering of diterpenoid synthases and the mevalonic acid pathway for miltiradiene production. J Am Chem Soc. 2012;134:3234-41 pubmed publisher..Previous engineering attempts mainly focused on the mevalonic acid (MVA) or methyl-d-erythritol phosphate (MEP) pathways responsible for the generation of precursors for ..
- Yoon S, Park H, Kim J, Lee S, Choi M, Kim J, et al. Increased beta-carotene production in recombinant Escherichia coli harboring an engineered isoprenoid precursor pathway with mevalonate addition. Biotechnol Prog. 2007;23:599-605 pubmed..5% (w/v) glycerol, beta-carotene production of 503 mg/L in concentration and 49.3 mg/g DCW in content was obtained at 144 h, which was the highest level of carotenoid production in E. coli ever reported in the literature. ..
- Hunter W. The non-mevalonate pathway of isoprenoid precursor biosynthesis. J Biol Chem. 2007;282:21573-7 pubmed..Detailed knowledge of the pathway may also be exploited to genetically modify microorganisms and plants to produce compounds of agricultural and medical interest. ..
- Khasnavis S, Pahan K. Sodium benzoate, a metabolite of cinnamon and a food additive, upregulates neuroprotective Parkinson disease protein DJ-1 in astrocytes and neurons. J Neuroimmune Pharmacol. 2012;7:424-35 pubmed publisher..Together, these results suggest that NaB upregulates DJ-1 via modulation of mevalonate metabolites and that p21(ras), but not p21(rac), is involved in the regulation of DJ-1. ..
- Ohto C, Muramatsu M, Obata S, Sakuradani E, Shimizu S. Overexpression of the gene encoding HMG-CoA reductase in Saccharomyces cerevisiae for production of prenyl alcohols. Appl Microbiol Biotechnol. 2009;82:837-45 pubmed publisher..On cultivation of the resultant transformant, in which the HMG-CoA reductase gene was overexpressed, in a 5-liter bench-scale jar fermenter for 7 d, the production of FOH, NOH, and GGOH reached 145.7, 98.8, and 2.46 mg/l, respectively. ..
- Bentley F, Zurbriggen A, Melis A. Heterologous expression of the mevalonic acid pathway in cyanobacteria enhances endogenous carbon partitioning to isoprene. Mol Plant. 2014;7:71-86 pubmed publisher..Evidence is presented to show heterologous genomic integration and cellular expression of the mevalonic acid (MVA) pathway genes in Synechocystis endowing a non-native pathway for carbon flux amplification to ..
- Fujimoto M, Oka T, Murata T, Hori M, Ozaki H. Fluvastatin inhibits mast cell degranulation without changing the cytoplasmic Ca2+ level. Eur J Pharmacol. 2009;602:432-8 pubmed publisher..The inhibitory effects were completely attenuated by simultaneous treatment with 100-1000 microM mevalonic acid for 4 h...
- Anthony J, Anthony L, Nowroozi F, Kwon G, Newman J, Keasling J. Optimization of the mevalonate-based isoprenoid biosynthetic pathway in Escherichia coli for production of the anti-malarial drug precursor amorpha-4,11-diene. Metab Eng. 2009;11:13-9 pubmed publisher..The methods demonstrated here are applicable for identifying and eliminating rate-limiting steps in other constructed biosynthetic pathways. ..
- Park D, So H, Lee J, Park H, Lee Y, Cho J, et al. Simvastatin treatment induces morphology alterations and apoptosis in murine cochlear neuronal cells. Acta Otolaryngol. 2009;129:166-74 pubmed publisher..We also found that simvastatin-induced VOT-33 apoptosis, as indicated by accumulation of the sub G0/G1 fraction, DNA-ladder formation, and caspase-3 activation. The above-mentioned effects were abolished by mevalonate treatment. ..
- Towler M, Weathers P. Evidence of artemisinin production from IPP stemming from both the mevalonate and the nonmevalonate pathways. Plant Cell Rep. 2007;26:2129-36 pubmed..This information will help advance our understanding of the regulation of in planta production of artemisinin. ..
- Buhaescu I, Izzedine H. Mevalonate pathway: a review of clinical and therapeutical implications. Clin Biochem. 2007;40:575-84 pubmed..Here we present a brief description of the biochemistry of the mevalonate pathway, together with a review of the current knowledge of the clinical and therapeutical implications of this fascinating and complex metabolic pathway. ..
- Castella B, Riganti C, Fiore F, Pantaleoni F, Canepari M, Peola S, et al. Immune modulation by zoledronic acid in human myeloma: an advantageous cross-talk between V?9V?2 T cells, ?? CD8+ T cells, regulatory T cells, and dendritic cells. J Immunol. 2011;187:1578-90 pubmed publisher..In conclusion, ZA has multiple immune modulatory activities that allow MM DC to effectively handle the concurrent activation of ?? T cells and MHC-restricted CD8(+) ?? antitumor effector T cells. ..
- Ghavami S, Mutawe M, Sharma P, Yeganeh B, McNeill K, Klonisch T, et al. Mevalonate cascade regulation of airway mesenchymal cell autophagy and apoptosis: a dual role for p53. PLoS ONE. 2011;6:e16523 pubmed publisher..These findings are relevant for the development of statin-based therapeutic approaches in obstructive airway disease. ..
- Ishibashi T. [Anti-atherosclerotic and anti-inflammatory effects of statin on cardiovascular disease and their mechanisms]. Nihon Rinsho. 2011;69:79-84 pubmed..Our recent animal study of intravenous administration of pravastatin supports the rapid pleiotropic effects of statin beyond cholesterol-lowering. ..
- Artsatbanov V, Vostroknutova G, Shleeva M, Goncharenko A, Zinin A, Ostrovsky D, et al. Influence of oxidative and nitrosative stress on accumulation of diphosphate intermediates of the non-mevalonate pathway of isoprenoid biosynthesis in corynebacteria and mycobacteria. Biochemistry (Mosc). 2012;77:362-71 pubmed publisher..A possible role of the MEP-pathway of isoprenoid biosynthesis and a role of its central intermediate MEcDP in bacterial response to nitrosative and oxidative stress is discussed. ..
- Haas D, Hoffmann G. Mevalonate kinase deficiency and autoinflammatory disorders. N Engl J Med. 2007;356:2671-3 pubmed
- Loiseau L, Gerez C, Bekker M, Ollagnier de Choudens S, Py B, Sanakis Y, et al. ErpA, an iron sulfur (Fe S) protein of the A-type essential for respiratory metabolism in Escherichia coli. Proc Natl Acad Sci U S A. 2007;104:13626-31 pubmed..coli. Surprisingly, the erpA gene maps at a distance from any other Fe-S biogenesis-related gene. ErpA is an A-type Fe-S protein that is characterized by an essential role in cellular metabolism. ..
- Balibar C, Shen X, Tao J. The mevalonate pathway of Staphylococcus aureus. J Bacteriol. 2009;191:851-61 pubmed publisher..We subsequently correlate these transcriptional changes with downstream metabolic consequences. ..
- Marcuzzi A, Piscianz E, Girardelli M, Crovella S, Pontillo A. Defect in mevalonate pathway induces pyroptosis in Raw 264.7 murine monocytes. Apoptosis. 2011;16:882-8 pubmed publisher..The involvement of pyroptosis is a novel hit in our cell model and opens discussions about its role in inflammatory cells with chemical or genetic inhibition of mevalonate pathway. ..
- Dueber J, Wu G, Malmirchegini G, Moon T, Petzold C, Ullal A, et al. Synthetic protein scaffolds provide modular control over metabolic flux. Nat Biotechnol. 2009;27:753-9 pubmed publisher..5 g/l) without the synthetic complex. These strategies should prove generalizeable to other metabolic pathways and programmable for fine-tuning pathway flux. ..
- Brahmachari S, Jana A, Pahan K. Sodium benzoate, a metabolite of cinnamon and a food additive, reduces microglial and astroglial inflammatory responses. J Immunol. 2009;183:5917-27 pubmed publisher..These results highlight a novel anti-inflammatory role of NaB via modulation of the mevalonate pathway and p21(ras)...
- Rico J, Pardo E, Orejas M. Enhanced production of a plant monoterpene by overexpression of the 3-hydroxy-3-methylglutaryl coenzyme A reductase catalytic domain in Saccharomyces cerevisiae. Appl Environ Microbiol. 2010;76:6449-54 pubmed publisher..In a haploid laboratory strain, engineering of this key step also improved linalool yield...
- Simon A, Drewe E, Van der Meer J, Powell R, Kelley R, Stalenhoef A, et al. Simvastatin treatment for inflammatory attacks of the hyperimmunoglobulinemia D and periodic fever syndrome. Clin Pharmacol Ther. 2004;75:476-83 pubmed..Simvastatin resulted in a drop in urinary mevalonic acid concentration in all patients and decreased the number of febrile days in 5 of 6 patients...
- Haas D, Hoffmann G. Mevalonate kinase deficiencies: from mevalonic aciduria to hyperimmunoglobulinemia D syndrome. Orphanet J Rare Dis. 2006;1:13 pubmed..In MVA, the diagnosis is established by detection of highly elevated levels of mevalonic acid excreted in urine...
- Pfleger B, Pitera D, Newman J, Martin V, Keasling J. Microbial sensors for small molecules: development of a mevalonate biosensor. Metab Eng. 2007;9:30-8 pubmed
- Kasahara H, Takei K, Ueda N, Hishiyama S, Yamaya T, Kamiya Y, et al. Distinct isoprenoid origins of cis- and trans-zeatin biosyntheses in Arabidopsis. J Biol Chem. 2004;279:14049-54 pubmed..Distinct origins of large proportions of DMAPP for tZ and cZ biosynthesis suggest that plants are able to separately modulate the level of these cytokinin species. ..
- Kotti T, Ramirez D, Pfeiffer B, Huber K, Russell D. Brain cholesterol turnover required for geranylgeraniol production and learning in mice. Proc Natl Acad Sci U S A. 2006;103:3869-74 pubmed..We conclude that cholesterol turnover in brain activates the mevalonate pathway and that a constant production of geranylgeraniol in a small subset of neurons is required for LTP and learning. ..
- Eisenreich W, Bacher A, Arigoni D, Rohdich F. Biosynthesis of isoprenoids via the non-mevalonate pathway. Cell Mol Life Sci. 2004;61:1401-26 pubmed..Detailed knowledge about the mechanisms of this novel route may benefit the development of novel antibiotics, antimalarials and herbicides. ..
- Kaneta S, Satoh K, Kano S, Kanda M, Ichihara K. All hydrophobic HMG-CoA reductase inhibitors induce apoptotic death in rat pulmonary vein endothelial cells. Atherosclerosis. 2003;170:237-43 pubmed..Endothelial cell apoptosis is underlying the improvement of the endothelial dysfunction with hydrophobic statins. ..
- Bate C, Salmona M, Diomede L, Williams A. Squalestatin cures prion-infected neurons and protects against prion neurotoxicity. J Biol Chem. 2004;279:14983-90 pubmed..These studies indicate a pivotal role for cholesterol-sensitive processes in controlling PrP(Sc) formation, and in the activation of signaling pathways associated with PrP-induced neuronal death. ..
- Jemal M, Schuster A, Whigan D. Liquid chromatography/tandem mass spectrometry methods for quantitation of mevalonic acid in human plasma and urine: method validation, demonstration of using a surrogate analyte, and demonstration of unacceptable matrix effect in spite of use of a s. Rapid Commun Mass Spectrom. 2003;17:1723-34 pubmed..mass spectrometry (LC/MS/MS) methods were developed and validated for the determination of mevalonic acid, an intermediate in the biosynthesis of cholesterol and therefore a useful biomarker in the development of ..
- Zheng Y, Plemenitas A, Fielding C, Peterlin B. Nef increases the synthesis of and transports cholesterol to lipid rafts and HIV-1 progeny virions. Proc Natl Acad Sci U S A. 2003;100:8460-5 pubmed..Thus, Nef also transports newly synthesized cholesterol to the site of viral budding. As such, it provides essential building blocks for the formation of viruses that replicate optimally in the host. ..
- Pitera D, Paddon C, Newman J, Keasling J. Balancing a heterologous mevalonate pathway for improved isoprenoid production in Escherichia coli. Metab Eng. 2007;9:193-207 pubmed..These results demonstrate that balancing carbon flux through the heterologous pathway is a key determinant in optimizing isoprenoid biosynthesis in microbial hosts. ..
- Thorpe J, Doitsidou M, Ho S, Raz E, Farber S. Germ cell migration in zebrafish is dependent on HMGCoA reductase activity and prenylation. Dev Cell. 2004;6:295-302 pubmed..Together with data from Drosophila (Santos and Lehmann, this issue), our results highlight a conserved role for protein geranylgeranylation in this context. ..
- Simon A, Kremer H, Wevers R, Scheffer H, De Jong J, van der Meer J, et al. Mevalonate kinase deficiency: Evidence for a phenotypic continuum. Neurology. 2004;62:994-7 pubmed..Mevalonate kinase deficiency should be considered in adult patients with fitting neurologic symptoms, with or without periodic fever attacks. ..
- Siddals K, Marshman E, Westwood M, Gibson J. Abrogation of insulin-like growth factor-I (IGF-I) and insulin action by mevalonic acid depletion: synergy between protein prenylation and receptor glycosylation pathways. J Biol Chem. 2004;279:38353-9 pubmed..These data imply that HMG-CoA reductase inhibitors disrupt IGF-I signaling by combined effects on Ras prenylation and IGF receptor glycosylation, whereas insulin signaling is only affected by disrupted receptor glycosylation. ..
- Wei H, Fang L, Song J, Chatterjee S. Statin-inhibited endothelial permeability could be associated with its effect on PECAM-1 in endothelial cells. FEBS Lett. 2005;579:1272-8 pubmed..All lovastatin's effects were abrogated by mevalonic acid. In resting HUVECs, geranylgeranyl pyrophosphate (GGPP), but not farnesyl pyrophosphate (FPP) (both are ..
- Swanson K, Hohl R. Anti-cancer therapy: targeting the mevalonate pathway. Curr Cancer Drug Targets. 2006;6:15-37 pubmed..These clinical trials are reviewed along with evaluation of some of the potential problems with these agents in their clinical application. ..
- Sakoda K, Yamamoto M, Negishi Y, Liao J, Node K, Izumi Y. Simvastatin decreases IL-6 and IL-8 production in epithelial cells. J Dent Res. 2006;85:520-3 pubmed..Our results may indicate an anti-inflammatory effect of simvastatin on human oral epithelial cells, apparently involving Rac1 GTPase inhibition. ..
- Saini G, Wani T, Gautam A, Varshney B, Ahmed T, Rajan K, et al. Validation of the LC-MS/MS method for the quantification of mevalonic acid in human plasma and determination of the matrix effect. J Lipid Res. 2006;47:2340-5 pubmed..liquid chromatography-tandem mass spectrometry (negative-ion electrospray ionization) methodology to determine mevalonic acid (MVA) in human plasma is described, and its application to the analysis of rat plasma MVA levels after ..