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 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.

Contents 1 Diversity 2 Clinical significance 3 References 4 External links

[edit] Diversity

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.)

[edit] 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]

[edit] References

[edit] External links

• MeSH Farnesyl-Diphosphate+Farnesyltransferase

v • d • e Transferases: alkyl and aryl (EC 2.5) 2.5.1 Dimethylallyltranstransferase - Thiaminase I - Methionine adenosyltransferase - Riboflavin synthase - Dihydropteroate synthetase - Spermidine synthase - Glutathione S-transferase - Farnesyl-diphosphate farnesyltransferase - Spermine synthase - Alkylglycerone phosphate synthase - Farnesyltransferase - Geranylgeranyltransferase type 1 - Porphobilinogen deaminase

v • d • e Metabolism: lipid metabolism · ketones/cholesterol synthesis enzymes/steroid metabolism Mevalonate pathway To HMG-CoA Acetyl-Coenzyme A acetyltransferase · HMG-CoA synthase (regulated step) Ketogenesis HMG-CoA lyase · 3-hydroxybutyrate dehydrogenase · Thiophorase To Mevalonic acid HMG-CoA reductase To DMAPP Mevalonate kinase · Phosphomevalonate kinase · Pyrophosphomevalonate decarboxylase · Isopentenyl-diphosphate delta isomerase Geranyl- Dimethylallyltranstransferase · Geranyl pyrophosphate To cholesterol To lanosterol Farnesyl-diphosphate farnesyltransferase · Squalene monooxygenase · Lanosterol synthase 7-Dehydrocholesterol path Lanosterol 14α-demethylase · Sterol-C5-desaturase-like · 7-Dehydrocholesterol reductase Desmosterol path 24-dehydrocholesterol reductase To Bile acids Cholesterol 7α-hydroxylase · Sterol 27-hydroxylase Steroidogenesis To pregnenolone Side-chain cleavage To corticosteroids aldosterone: 18-hydroxylase cortisol/cortisone: 17α-hydroxylase · 11β dehydrogenase (HSD11B1, HSD11B2) both: 3β dehydrogenase · 21α-hydroxylase · 11β-hydroxylase To sex hormones To androgens 17α-hydroxylase/17,20 lyase · 3β dehydrogenase · 17β dehydrogenase · 5α reductase To estrogens Aromatase Other/ungrouped Steroid sulfatase · Steroidogenic acute regulatory protein see also intermediates, disorders

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