The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 

Links

 

Gene Review

Fdft1  -  farnesyl diphosphate farnesyl transferase 1

Rattus norvegicus

Synonyms: FPP:FPP farnesyltransferase, Farnesyl-diphosphate farnesyltransferase, SQS, SS, Squalene synthase
 
 
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.
 

Disease relevance of Fdft1

  • Surgical denervation of the adult SCG increased ganglion levels of preprosomatostatin (SS) mRNA more than 11-fold, and levels of the mRNA remained elevated 14 days after surgery [1].
 

High impact information on Fdft1

  • Cataract onset was associated with the specific combination of Lss and Fdft1 mutant alleles that decreased cholesterol levels in cataractous lenses to about 57% of normal [2].
  • The importance of SQS in cholesterol metabolism has stimulated research on the mechanism, structure, and regulation of the enzyme [3].
  • SQS produces squalene, a C30 isoprenoid, in a two-step reaction in which two molecules of farnesyl diphosphate are condensed head to head [3].
  • Regulation of SQS is thought to direct proximal intermediates in the pathway into either sterol or nonsterol branches in response to changing cellular requirements [3].
  • Site-directed mutagenesis of rat SQS has identified conserved Tyr, Phe, and Asp residues that are essential for function [3].
 

Biological context of Fdft1

 

Anatomical context of Fdft1

  • A soluble squalene synthetase protein with an estimated mass of 32-35 kDa, as determined by gel filtration chromatography on Sephacryl S-200 column, was solubilized out of the microsomes by controlled proteolysis with trypsin [9].
  • Isoprenoid biosynthesis in rat liver peroxisomes. Characterization of cis-prenyltransferase and squalene synthetase [10].
  • ER-28448 inhibited SQS in rat liver microsome with an IC(50) value of 3.6 nm [11].
  • The present study deals with the mechanism of the inhibition of triglyceride biosynthesis by the SQS inhibitors ER-27856 and RPR-107393 in rat primary cultured hepatocytes [12].
  • SS mRNA and SS increased in the cortex and striatum, while only SS increased in the hippocampus [13].
 

Associations of Fdft1 with chemical compounds

  • Rat hepatic microsomal squalene synthetase (EC 2.5.1.21) was induced 25-fold by feeding rats with diet containing the hydroxymethylglutaryl-coenzyme A reductase inhibitor, fluvastatin, and cholestyramine, a bile acid sequestrant [9].
  • Inhibition of mammalian squalene synthetase activity by zaragozic acid A is a result of competitive inhibition followed by mechanism-based irreversible inactivation [14].
  • Isolated peroxisomes were able to utilize [3H]isopentenyl diphosphate to synthesize farnesyl diphosphate, which then was utilized as substrate by both the peroxisomal squalene synthetase and cis-prenyltransferase [10].
  • These results suggest that SQS inhibitors reduce triglyceride biosynthesis by suppressing fatty acid biosynthesis via an increase in intracellular farnesol and its derivatives [12].
  • HMG-CoA reductase regulation: use of structurally diverse first half-reaction squalene synthetase inhibitors to characterize the site of mevalonate-derived nonsterol regulator production in cultured IM-9 cells [7].
 

Other interactions of Fdft1

 

Analytical, diagnostic and therapeutic context of Fdft1

References

  1. Differences in the effects of membrane depolarization on levels of preprosomatostatin mRNA and tyrosine hydroxylase mRNA in rat sympathetic neurons in vivo and in culture. Spiegel, K., Kremer, N.E., Kessler, J.A. Brain Res. Mol. Brain Res. (1989) [Pubmed]
  2. Lanosterol synthase mutations cause cholesterol deficiency-associated cataracts in the Shumiya cataract rat. Mori, M., Li, G., Abe, I., Nakayama, J., Guo, Z., Sawashita, J., Ugawa, T., Nishizono, S., Serikawa, T., Higuchi, K., Shumiya, S. J. Clin. Invest. (2006) [Pubmed]
  3. Squalene synthase: structure and regulation. Tansey, T.R., Shechter, I. Prog. Nucleic Acid Res. Mol. Biol. (2001) [Pubmed]
  4. Regulation of cholesterol 7 alpha-hydroxylase expression by sterols in primary rat hepatocyte cultures. Doerner, K.C., Gurley, E.C., Vlahcevic, Z.R., Hylemon, P.B. J. Lipid Res. (1995) [Pubmed]
  5. Synthesis and activity of a novel series of 3-biarylquinuclidine squalene synthase inhibitors. Brown, G.R., Clarke, D.S., Foubister, A.J., Freeman, S., Harrison, P.J., Johnson, M.C., Mallion, K.B., McCormick, J., McTaggart, F., Reid, A.C., Smith, G.J., Taylor, M.J. J. Med. Chem. (1996) [Pubmed]
  6. The squalestatins: decarboxy and 4-deoxy analogues as potent squalene synthase inhibitors. Chan, C., Andreotti, D., Cox, B., Dymock, B.W., Hutson, J.L., Keeling, S.E., McCarthy, A.D., Procopiou, P.A., Ross, B.C., Sareen, M., Scicinski, J.J., Sharratt, P.J., Snowden, M.A., Watson, N.S. J. Med. Chem. (1996) [Pubmed]
  7. HMG-CoA reductase regulation: use of structurally diverse first half-reaction squalene synthetase inhibitors to characterize the site of mevalonate-derived nonsterol regulator production in cultured IM-9 cells. Petras, S.F., Lindsey, S., Harwood, H.J. J. Lipid Res. (1999) [Pubmed]
  8. Inhibition of squalene synthase in vitro by 3-(biphenyl-4-yl)-quinuclidine. Ward, W.H., Holdgate, G.A., Freeman, S., McTaggart, F., Girdwood, P.A., Davidson, R.G., Mallion, K.B., Brown, G.R., Eakin, M.A. Biochem. Pharmacol. (1996) [Pubmed]
  9. Solubilization, purification, and characterization of a truncated form of rat hepatic squalene synthetase. Shechter, I., Klinger, E., Rucker, M.L., Engstrom, R.G., Spirito, J.A., Islam, M.A., Boettcher, B.R., Weinstein, D.B. J. Biol. Chem. (1992) [Pubmed]
  10. Isoprenoid biosynthesis in rat liver peroxisomes. Characterization of cis-prenyltransferase and squalene synthetase. Ericsson, J., Appelkvist, E.L., Thelin, A., Chojnacki, T., Dallner, G. J. Biol. Chem. (1992) [Pubmed]
  11. Effect of ER-27856, a novel squalene synthase inhibitor, on plasma cholesterol in rhesus monkeys: comparison with 3-hydroxy-3-methylglutaryl-coa reductase inhibitors. Hiyoshi, H., Yanagimachi, M., Ito, M., Ohtsuka, I., Yoshida, I., Saeki, T., Tanaka, H. J. Lipid Res. (2000) [Pubmed]
  12. Squalene synthase inhibitors suppress triglyceride biosynthesis through the farnesol pathway in rat hepatocytes. Hiyoshi, H., Yanagimachi, M., Ito, M., Yasuda, N., Okada, T., Ikuta, H., Shinmyo, D., Tanaka, K., Kurusu, N., Yoshida, I., Abe, S., Saeki, T., Tanaka, H. J. Lipid Res. (2003) [Pubmed]
  13. Amygdaloid kindling of rats increases preprosomatostatin mRNA and somatostatin without affecting glutamic acid decarboxylase (GAD) mRNA or GAD. Shinoda, H., Schwartz, J.P., Nadi, N.S. Brain Res. Mol. Brain Res. (1989) [Pubmed]
  14. Inhibition of mammalian squalene synthetase activity by zaragozic acid A is a result of competitive inhibition followed by mechanism-based irreversible inactivation. Lindsey, S., Harwood, H.J. J. Biol. Chem. (1995) [Pubmed]
  15. Chromosomal localization of genes involved in biosynthesis, metabolism or transport of cholesterol in the rat. Bonné, A.C., den Bieman, M.G., Gillissen, G.F., van Lith, H.A., van Zutphen, L.F. Cytogenet. Genome Res. (2002) [Pubmed]
  16. Determination of isopentenyl diphosphate and farnesyl diphosphate in tissue samples with a comment on secondary regulation of polyisoprenoid biosynthesis. Bruenger, E., Rilling, H.C. Anal. Biochem. (1988) [Pubmed]
  17. Effects of AP-V and bicuculline on somatostatin-positive neurons in hypothalamus of rats subjected to acute hypobaric hypoxia. Fan, X.T., Ruan, H.Z., Xu, H.W., Zhang, J.H., Wu, X.G. Acta Pharmacol. Sin. (2001) [Pubmed]
 
WikiGenes - Universities