Transferases;
Transferring alkyl or aryl groups, other than methyl groups;
Transferring alkyl or aryl groups, other than methyl groups (only sub-subclass identified to date)

(2E,6E)-farnesyl-diphosphate:(2E,6E)-farnesyl-diphosphate farnesyltransferase

2 (2E,6E)-farnesyl diphosphate + NAD(P)H + H+ = squalene + 2 diphosphate + NAD(P)+ (overall reaction) [RN:R06223];
(1a) 2 (2E,6E)-farnesyl diphosphate = diphosphate + presqualene diphosphate [RN:R00702];
(1b) presqualene diphosphate + NAD(P)H + H+ = squalene + diphosphate + NAD(P)+ [RN:R02872]

R00702 R02872 R06223

(2E,6E)-farnesyl diphosphate [CPD:C00448];
NADH [CPD:C00004];
NADPH [CPD:C00005];
H+ [CPD:C00080];
presqualene diphosphate [CPD:C03428]

This microsomal enzyme catalyses the first committed step in the biosynthesis of sterols. The enzyme from yeast requires either Mg2+ or Mn2+ for activity. In the absence of NAD(P)H, presqualene diphosphate (PSPP) is accumulated. When NAD(P)H is present, presqualene diphosphate does not dissociate from the enzyme during the synthesis of squalene from farnesyl diphosphate (FPP) [8]. High concentrations of FPP inhibit the production of squalene but not of PSPP [8].

EC 2.5.1.21 created 1976, modified 2005, modified 2012

1  [PMID:3805037]

Kuswik-Rabiega G, Rilling HC.

Squalene synthetase. Solubilization and partial purification of squalene synthetase, copurification of presqualene pyrophosphate and squalene synthetase activities.

J Biol Chem 262:1505-9 (1987)

2  [PMID:1527001]

Ericsson J, Appelkvist EL, Thelin A, Chojnacki T, Dallner G.

Isoprenoid biosynthesis in rat liver peroxisomes. Characterization of cis-prenyltransferase and squalene synthetase.

J Biol Chem 267:18708-14 (1992)

3  [PMID:11111077]

Tansey TR, Shechter I.

Structure and regulation of mammalian squalene synthase.

Biochim Biophys Acta 1529:49-62 (2000)
DOI:10.1016/S1388-1981(00)00137-2

4  [PMID:8239656]

LoGrasso PV, Soltis DA, Boettcher BR.

Overexpression, purification, and kinetic characterization of a carboxyl-terminal-truncated yeast squalene synthetase.

Arch Biochem Biophys 307:193-9 (1993)
DOI:10.1006/abbi.1993.1578

5  [PMID:1569107]

Shechter I, Klinger E, Rucker ML, Engstrom RG, Spirito JA, Islam MA, Boettcher BR, Weinstein DB.

Solubilization, purification, and characterization of a truncated form of rat hepatic squalene synthetase.

J Biol Chem 267:8628-35 (1992)

[rno:29580]

6  [PMID:26684]

Agnew WS, Popjak G.

Squalene synthetase. Stoichiometry and kinetics of presqualene pyrophosphate and squalene synthesis by yeast microsomes.

J Biol Chem 253:4566-73 (1978)

7  [PMID:10896663]

Pandit J, Danley DE, Schulte GK, Mazzalupo S, Pauly TA, Hayward CM, Hamanaka ES, Thompson JF, Harwood HJ Jr.

Crystal structure of human squalene synthase. A key enzyme in cholesterol biosynthesis.

J Biol Chem 275:30610-7 (2000)
DOI:10.1074/jbc.M004132200

[hsa:2222]

8  [PMID:10677224]

Radisky ES, Poulter CD.

Squalene synthase: steady-state, pre-steady-state, and isotope-trapping studies.

Biochemistry 39:1748-60 (2000)
DOI:10.1021/bi9915014