IntEnz

EC 2.5.1.21 - Squalene synthase

IntEnz Enzyme Nomenclature
EC 2.5.1.21

Names

Reactions

• (1) 2 farnesyl diphosphate + NAD(P)H + H+ = squalene + 2 diphosphate + NAD(P)+
•   (1a) 2 farnesyl diphosphate = diphosphate + presqualene diphosphate
•   (1b) presqualene diphosphate + NAD(P)H + H+ = squalene + diphosphate + NAD(P)+

Cofactor

• Mn²⁺ Mg²⁺

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

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 : 1505-1509 (1987). [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 : 18708-18714 (1992). [PMID: 1527001]
3. Tansey, T.R. and Shechter, I.
   Structure and regulation of mammalian squalene synthase.
   Biochim. Biophys. Acta 1529 : 49-62 (2001). [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 : 193-199 (1993). [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 : 8628-8635 (1992). [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 : 4566-4573 (1978). [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., Harwood, H. J.
   Crystal structure of human squalene synthase. A key enzyme in cholesterol biosynthesis.
   J. Biol. Chem. 275 : 30610-30617 (2000). [PMID: 10896663]
8. Radisky, E.S. and Poulter, C.D.
   Squalene synthase: steady-state, pre-steady-state, and isotope-trapping studies.
   Biochemistry 39 : 1748-1760 (2000). [PMID: 10677224]

[EC 2.5.1.21 created 1976, modified 2005]