Squalene synthase inhibitor

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farnesyl-diphosphate farnesyltransferase 1
Identifiers
Symbol FDFT1
Entrez 2222
HUGO 3629
OMIM 184420
RefSeq NM_004462
UniProt P37268
Other data
EC number 2.5.1.21
Locus Chr. 8 p23.1-p22

Farnesyl-diphosphate farnesyltransferase (FDFT1) (or squalene synthase (SQS)) is an enzyme which converts two units of farnesyl pyrophosphate into squalene.

Squalene synthase is considered to be an enzyme of eukaryotes or advanced organisms, although at least one prokaryote has been shown to possess a functionally similar enzyme.

It has been described as the first dedicated enzyme of sterol (i.e. cholesterol, etc.) synthesis since the squalene formed by it is exclusively routed into various sterols via a complex, multi-step pathway.

Mechanistically and structurally, squalene synthase most closely resembles phytoene syntase, which serves a similar role in many plants in the elaboration of phytoene, a precursor of many carotenoid compounds. (Carotenoids are the colorful pigments present in most vegetables.)

Inhibition of squalene synthase, e.g. by lapaquistat, is under investigation as a method of lowering cholesterol levels in the prevention of cardiovascular disease.[1] Squalene synthase homolog inhibition in Staphylococcus aureus is currently being investigated as a virulence factor-based antibacterial therapy. [2]

References

  1. ^ Davidson, MH (Jan 2007). "Squalene synthase inhibition: a novel target for the management of dyslipidemia". Curr Atheroscler Rep 9 (1): 78–80. doi:10.1007/BF02693932. PMID 17169251. 
  2. ^ Liu et al (2008). "A Cholesterol Biosynthesis Inhibitor Blocks Staphylococcus aureus Virulence". Science 319: 1391. doi:10.1126/science.1153018. PMID 18276850. 

External links

 This transferase article is a stub. You can help Wikipedia by expanding it.
v • d • e
Alkyl and aryl transferases (EC 2.5)
v • d • e
Metabolism: lipid metabolism - ketones/mevalonate pathway/cholesterol synthesis enzymes
To HMG-CoA
Ketogenesis
To Mevalonic acid
To DMAPP
To Cholesterols
To Bile acids
see also intermediates

Wikipedia content modification information:

  • This page was last modified on 8 June 2008, at 08:01.

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