Reaction: 2 (2E,6E)-farnesyl diphosphate + NAD(P)H + H+ = squalene + 2 diphosphate + NAD(P)+ (overall reaction)
(1a) 2 (2E,6E)-farnesyl diphosphate = diphosphate + presqualene diphosphate
(1b) presqualene diphosphate + NAD(P)H + H+ = squalene + diphosphate + NAD(P)+
For diagram of reaction click here
Other name(s): farnesyltransferase; presqualene-diphosphate synthase; presqualene synthase; squalene synthetase; farnesyl-diphosphate farnesyltransferase; SQS
Systematic name: (2E,6E)-farnesyl-diphosphate:(2E,6E)-farnesyl-diphosphate farnesyltransferase
Comments: 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].
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9077-14-9
References:
1. Kuswick-Rabiega, G. and Rilling, H.C. Squalene synthetase. Solubilization and partial purification of squalene synthetase, copurification of presqualene pyrophosphate and squalene synthetase activities. J. Biol. Chem. 262 (1987) 1505-1509. [PMID: 3805037]
2. Ericsson, J., Appelkvist, E.L., Thelin, A., Chojnacki, T. and Dallner, G. Isoprenoid biosynthesis in rat liver peroxisomes. Characterization of cis-prenyltransferase and squalene synthetase. J. Biol. Chem. 267 (1992) 18708-18714. [PMID: 1527001]
3. Tansey, T.R. and Shechter, I. Structure and regulation of mammalian squalene synthase. Biochim. Biophys. Acta 1529 (2000) 49-62. [PMID: 11111077]
4. LoGrasso, P.V., Soltis, D.A. and Boettcher, B.R. Overexpression, purification, and kinetic characterization of a carboxyl-terminal-truncated yeast squalene synthetase. Arch. Biochem. Biophys. 307 (1993) 193-199. [PMID: 8239656]
5. Shechter, I., Klinger, E., Rucker, M.L., Engstrom, R.G., Spirito, J.A., Islam, M.A., Boettcher, B.R. and Weinstein, D.B. Solubilization, purification, and characterization of a truncated form of rat hepatic squalene synthetase. J. Biol. Chem. 267 (1992) 8628-8635. [PMID: 1569107]
6. Agnew, W.S. and Popják, G. Squalene synthetase. Stoichiometry and kinetics of presqualene pyrophosphate and squalene synthesis by yeast microsomes. J. Biol. Chem. 253 (1978) 4566-4573. [PMID: 26684]
7. Pandit, J., Danley, D.E., Schulte, G.K., Mazzalupo, S., Pauly, T.A., Hayward, C.M., Hamanaka, E.S., Thompson, J.F. and Harwood, H.J., Jr. Crystal structure of human squalene synthase. A key enzyme in cholesterol biosynthesis. J. Biol. Chem. 275 (2000) 30610-30617. [PMID: 10896663]
8. Radisky, E.S. and Poulter, C.D. Squalene synthase: steady-state, pre-steady-state, and isotope-trapping studies. Biochemistry 39 (2000) 1748-1760. [PMID: 10677224]