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

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


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.



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.

In terms of structure and mechanics, 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.)

Clinical significance

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][2] It has also been suggested that variants in this enzyme may be part of a genetic association with hypercholesterolemia.[3]

Squalene synthase homolog inhibition in Staphylococcus aureus is currently being investigated as a virulence factor-based antibacterial therapy. [4]


  1. ^ Davidson, MH (January 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. ^ Charlton-Menys V, Durrington PN (2007). "Squalene synthase inhibitors : clinical pharmacology and cholesterol-lowering potential". Drugs 67 (1): 11–6. PMID 17209661.  
  3. ^ Do R, Kiss RS, Gaudet D, Engert JC (January 2009). "Squalene synthase: a critical enzyme in the cholesterol biosynthesis pathway". Clin. Genet. 75 (1): 19–29. doi:10.1111/j.1399-0004.2008.01099.x. PMID 19054015.  
  4. ^ Liu et al. (2008). "A Cholesterol Biosynthesis Inhibitor Blocks Staphylococcus aureus Virulence". Science 319: 1391. doi:10.1126/science.1153018. PMID 18276850.  

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