The Enzyme Database

Displaying entries 51-77 of 77.

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EC 2.3.1.26     
Accepted name: sterol O-acyltransferase
Reaction: a long-chain acyl-CoA + a sterol = CoA + a long-chain 3-hydroxysterol ester
Other name(s): cholesterol acyltransferase; sterol-ester synthase; acyl coenzyme A-cholesterol-O-acyltransferase; acyl-CoA:cholesterol acyltransferase; ACAT; acylcoenzyme A:cholesterol O-acyltransferase; cholesterol ester synthase; cholesterol ester synthetase; cholesteryl ester synthetase; SOAT1 (gene name); SOAT2 (gene name); ARE1 (gene name); ARE2 (gene name); acyl-CoA:cholesterol O-acyltransferase
Systematic name: long-chain acyl-CoA:sterol O-acyltransferase
Comments: The enzyme catalyses the formation of sterol esters from a sterol and long-chain fatty acyl-coenzyme A. The enzyme from yeast, but not from mammals, prefers monounsaturated acyl-CoA. In mammals the enzyme acts mainly on cholesterol and forms cholesterol esters that are stored in cytosolic droplets, which may serve to protect cells from the toxicity of free cholesterol. In macrophages, the accumulation of cytosolic droplets of cholesterol esters results in the formation of `foam cells’, a hallmark of early atherosclerotic lesions. In hepatocytes and enterocytes, cholesterol esters can be incorporated into apolipoprotein B-containing lipoproteins for secretion from the cell.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9027-63-8
References:
1.  Spector, A.A., Mathur, S.N. and Kaduce, T.L. Role of acylcoenzyme A: cholesterol O-acyltransferase in cholesterol metabolism. Prog. Lipid Res. 18 (1979) 31–53. [DOI] [PMID: 42927]
2.  Taketani, S., Nishino, T. and Katsuki, H. Characterization of sterol-ester synthetase in Saccharomyces cerevisiae. Biochim. Biophys. Acta 575 (1979) 148–155. [DOI] [PMID: 389289]
3.  Lee, O., Chang, C.C., Lee, W. and Chang, T.Y. Immunodepletion experiments suggest that acyl-coenzyme A:cholesterol acyltransferase-1 (ACAT-1) protein plays a major catalytic role in adult human liver, adrenal gland, macrophages, and kidney, but not in intestines. J. Lipid Res. 39 (1998) 1722–1727. [PMID: 9717734]
4.  Yang, H., Cromley, D., Wang, H., Billheimer, J.T. and Sturley, S.L. Functional expression of a cDNA to human acyl-coenzyme A:cholesterol acyltransferase in yeast. Species-dependent substrate specificity and inhibitor sensitivity. J. Biol. Chem. 272 (1997) 3980–3985. [PMID: 9020103]
5.  Chang, C.C., Lee, C.Y., Chang, E.T., Cruz, J.C., Levesque, M.C. and Chang, T.Y. Recombinant acyl-CoA:cholesterol acyltransferase-1 (ACAT-1) purified to essential homogeneity utilizes cholesterol in mixed micelles or in vesicles in a highly cooperative manner. J. Biol. Chem. 273 (1998) 35132–35141. [PMID: 9857049]
6.  Das, A., Davis, M.A. and Rudel, L.L. Identification of putative active site residues of ACAT enzymes. J. Lipid Res. 49 (2008) 1770–1781. [PMID: 18480028]
[EC 2.3.1.26 created 1972, modified 2019]
 
 
EC 2.3.1.43     
Accepted name: phosphatidylcholine—sterol O-acyltransferase
Reaction: phosphatidylcholine + a sterol = 1-acylglycerophosphocholine + a sterol ester
Other name(s): lecithin—cholesterol acyltransferase; phospholipid—cholesterol acyltransferase; LCAT (lecithin-cholesterol acyltransferase); lecithin:cholesterol acyltransferase; lysolecithin acyltransferase
Systematic name: phosphatidylcholine:sterol O-acyltransferase
Comments: Palmitoyl, oleoyl and linoleoyl residues can be transferred; a number of sterols, including cholesterol, can act as acceptors. The bacterial enzyme also catalyses the reactions of EC 3.1.1.4 phospholipase A2 and EC 3.1.1.5 lysophospholipase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9031-14-5
References:
1.  Bartlett, K., Keat, M.J. and Mercer, E.I. Biosynthesis of sterol esters in Phycomyces blakesleeanus. Phytochemistry 13 (1974) 1107–1113.
2.  Buckley, J.T., Halasa, L.N. and Macintyre, S. Purification and partial characterization of a bacterial phospholipid: cholesterol acyltransferase. J. Biol. Chem. 257 (1982) 3320–3325. [PMID: 7061477]
3.  Glomset, J.A.J. The plasma lecithins:cholesterol acyltransferase reaction. Lipid Res. 9 (1968) 155–167. [PMID: 4868699]
4.  Vahouny, G.V. and Tradwell, C.R. Enzymatic synthesis and hydrolysis of cholesterol esters. Methods Biochem. Anal. 16 (1968) 219–272. [PMID: 4877146]
[EC 2.3.1.43 created 1972, modified 1976]
 
 
EC 2.3.1.65     
Accepted name: bile acid-CoA:amino acid N-acyltransferase
Reaction: choloyl-CoA + glycine = CoA + glycocholate
For diagram of the biosynthesis of cholic-acid conjugates, click here
Glossary: choloyl-CoA = 3α,7α,12α-trihydroxy-5β-cholan-24-oyl-CoA
Other name(s): glycine—taurine N-acyltransferase; amino acid N-choloyltransferase; BAT; glycine N-choloyltransferase; BACAT; cholyl-CoA glycine-taurine N-acyltransferase; cholyl-CoA:taurine N-acyltransferase
Systematic name: choloyl-CoA:glycine N-choloyltransferase
Comments: Also acts on CoA derivatives of other bile acids. Taurine and 2-fluoro-β-alanine can act as substrates, but more slowly [4]. The enzyme can also conjugate fatty acids to glycine and can act as a very-long-chain acyl-CoA thioesterase [7]. Bile-acid—amino-acid conjugates serve as detergents in the gastrointestinal tract, solubilizing long chain fatty acids, mono- and diglycerides, fat-soluble vitamins and cholesterol [4]. This is the second enzyme in a two-step process leading to the conjugation of bile acids with amino acids; the first step is the conversion of bile acids into their acyl-CoA thioesters, which is catalysed by EC 6.2.1.7, cholate—CoA ligase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 65979-40-0
References:
1.  Czuba, B. and Vessey, D.A. Kinetic characterization of cholyl-CoA glycine-taurine N-acyltransferase from bovine liver. J. Biol. Chem. 255 (1980) 5296–5299. [PMID: 7372637]
2.  Jordan, T.W., Lee, R. and Lim, W.C. Isoelectric focussing of soluble and particulate benzoyl-CoA and cholyl-CoA:amino acid N-acyltransferases from rat liver. Biochem. Int. 1 (1980) 325–330.
3.  Vessey, D.A. The co-purification and common identity of cholyl CoA:glycine- and cholyl CoA:taurine-N-acyltransferase activities from bovine liver. J. Biol. Chem. 254 (1979) 2059–2063. [PMID: 422567]
4.  Johnson, M.R., Barnes, S., Kwakye, J.B. and Diasio, R.B. Purification and characterization of bile acid-CoA:amino acid N-acyltransferase from human liver. J. Biol. Chem. 266 (1991) 10227–10233. [PMID: 2037576]
5.  Falany, C.N., Xie, X., Wheeler, J.B., Wang, J., Smith, M., He, D. and Barnes, S. Molecular cloning and expression of rat liver bile acid CoA ligase. J. Lipid Res. 43 (2002) 2062–2071. [PMID: 12454267]
6.  He, D., Barnes, S. and Falany, C.N. Rat liver bile acid CoA:amino acid N-acyltransferase: expression, characterization, and peroxisomal localization. J. Lipid Res. 44 (2003) 2242–2249. [DOI] [PMID: 12951368]
7.  O'Byrne, J., Hunt, M.C., Rai, D.K., Saeki, M. and Alexson, S.E. The human bile acid-CoA:amino acid N-acyltransferase functions in the conjugation of fatty acids to glycine. J. Biol. Chem. 278 (2003) 34237–34244. [DOI] [PMID: 12810727]
[EC 2.3.1.65 created 1983, modified 2005]
 
 
EC 2.3.1.73     
Accepted name: diacylglycerol—sterol O-acyltransferase
Reaction: a 1,2-diacyl-sn-glycerol + sterol = a 1-acyl-sn-glycerol + sterol ester
Other name(s): 1,2-diacyl-sn-glycerol:sterol acyl transferase
Systematic name: 1,2-diacyl-sn-glycerol:sterol O-acyltransferase
Comments: Cholesterol, sitosterol, campesterol and diacylglycerol can act as acceptors. Transfers a number of long-chain fatty acyl groups.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 79586-23-5
References:
1.  Bartlett, K., Keat, M.J. and Mercer, E.I. Biosynthesis of sterol esters in Phycomyces blakesleeanus. Phytochemistry 13 (1974) 1107–1113.
2.  Garcia, R.E. and Mudd, J.B. Metabolism of monoacylglycerol and diacylglycerol by enzyme preparations from spinach leaves. Arch. Biochem. Biophys. 191 (1978) 487–493. [DOI] [PMID: 742884]
3.  Garcia, R.E. and Mudd, J.B. 1,2-Diacyl-sn-glycerol:sterol acyl transferase from spinach leaves (Spinacia oleracea L.). Methods Enzymol. 71 (1981) 768–772.
[EC 2.3.1.73 created 1984]
 
 
EC 2.3.2.36     
Accepted name: RING-type E3 ubiquitin transferase (cysteine targeting)
Reaction: [E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-cysteine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-S-ubiquitinyl-L-cysteine
Glossary: RING = Really Interesting New Gene
Other name(s): RING E3 ligase (misleading)
Systematic name: [E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine:[acceptor protein] ubiquitin transferase (thioester bond-froming; RING-type)
Comments: This relatively rare subpopulation of RING-type E3 ubiquitin transferases (cf. EC 2.3.2.27), found in mammals and herpes viruses, can transfer ubiquitin to a cysteine residue in target proteins. Additional ubiquitin molecules are polymerized on top of the initial ubiquitin molecule by formation of an isopeptide linkage with lysine48 in the pre-attached ubiquitin [2].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB
References:
1.  Cadwell, K. and Coscoy, L. Ubiquitination on nonlysine residues by a viral E3 ubiquitin ligase. Science 309 (2005) 127–130. [DOI] [PMID: 15994556]
2.  Wang, Y.J., Bian, Y., Luo, J., Lu, M., Xiong, Y., Guo, S.Y., Yin, H.Y., Lin, X., Li, Q., Chang, C.CY., Chang, T.Y., Li, B.L. and Song, B.L. Cholesterol and fatty acids regulate cysteine ubiquitylation of ACAT2 through competitive oxidation. Nat. Cell Biol. 19 (2017) 808–819. [DOI] [PMID: 28604676]
3.  Zhou, Z.S., Li, M.X., Liu, J., Jiao, H., Xia, J.M., Shi, X.J., Zhao, H., Chu, L., Liu, J., Qi, W., Luo, J. and Song, B.L. Competitive oxidation and ubiquitylation on the evolutionarily conserved cysteine confer tissue-specific stabilization of Insig-2. Nat. Commun. 11:379 (2020). [DOI] [PMID: 31953408]
[EC 2.3.2.36 created 2020]
 
 
EC 2.4.1.274     
Accepted name: glucosylceramide β-1,4-galactosyltransferase
Reaction: UDP-α-D-galactose + β-D-glucosyl-(1↔1)-ceramide = UDP + β-D-galactosyl-(1→4)-β-D-glucosyl-(1↔1)-ceramide
For diagram of glycolipid biosynthesis, click here
Other name(s): lactosylceramide synthase; uridine diphosphate-galactose:glucosyl ceramide β 1-4 galactosyltransferase; UDP-Gal:glucosylceramide β1→4galactosyltransferase; GalT-2 (misleading); UDP-galactose:β-D-glucosyl-(1↔1)-ceramide β-1,4-galactosyltransferase
Systematic name: UDP-α-D-galactose:β-D-glucosyl-(1↔1)-ceramide 4-β-D-galactosyltransferase
Comments: Involved in the synthesis of several different major classes of glycosphingolipids.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  Chatterjee, S. and Castiglione, E. UDPgalactose:glucosylceramide β1→4-galactosyltransferase activity in human proximal tubular cells from normal and familial hypercholesterolemic homozygotes. Biochim. Biophys. Acta 923 (1987) 136–142. [DOI] [PMID: 3099851]
2.  Trinchera, M., Fiorilli, A. and Ghidoni, R. Localization in the Golgi apparatus of rat liver UDP-Gal:glucosylceramide β1→4galactosyltransferase. Biochemistry 30 (1991) 2719–2724. [PMID: 1900430]
3.  Chatterjee, S., Ghosh, N. and Khurana, S. Purification of uridine diphosphate-galactose:glucosyl ceramide, β 1-4 galactosyltransferase from human kidney. J. Biol. Chem. 267 (1992) 7148–7153. [PMID: 1551920]
4.  Nomura, T., Takizawa, M., Aoki, J., Arai, H., Inoue, K., Wakisaka, E., Yoshizuka, N., Imokawa, G., Dohmae, N., Takio, K., Hattori, M. and Matsuo, N. Purification, cDNA cloning, and expression of UDP-Gal: glucosylceramide β-1,4-galactosyltransferase from rat brain. J. Biol. Chem. 273 (1998) 13570–13577. [DOI] [PMID: 9593693]
5.  Takizawa, M., Nomura, T., Wakisaka, E., Yoshizuka, N., Aoki, J., Arai, H., Inoue, K., Hattori, M. and Matsuo, N. cDNA cloning and expression of human lactosylceramide synthase. Biochim. Biophys. Acta 1438 (1999) 301–304. [DOI] [PMID: 10320813]
[EC 2.4.1.274 created 2011]
 
 
EC 2.5.1.21     
Accepted name: squalene synthase
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 squalene, phytoene and 4,4′-diapophytoene biosynthesis, 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. [DOI] [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. [DOI] [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. [DOI] [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. [DOI] [PMID: 10677224]
[EC 2.5.1.21 created 1976, modified 2005, modified 2012]
 
 
EC 2.5.1.96     
Accepted name: 4,4′-diapophytoene synthase
Reaction: 2 (2E,6E)-farnesyl diphosphate = 15-cis-4,4′-diapophytoene + 2 diphosphate (overall reaction)
(1a) 2 (2E,6E)-farnesyl diphosphate = diphosphate + presqualene diphosphate
(1b) presqualene diphosphate = 15-cis-4,4′-diapophytoene + diphosphate
For diagram of squalene, phytoene and 4,4′-diapophytoene biosynthesis, click here
Other name(s): dehydrosqualene synthase; DAP synthase; C30 carotene synthase; CrtM
Systematic name: farnesyl-diphosphate:farnesyl-diphosphate farnesyltransferase (15-cis-4,4′-diapophytoene-forming)
Comments: Requires Mn2+. Typical of Staphylococcus aureus and some other bacteria such as Heliobacillus sp.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB
References:
1.  Umeno, D., Tobias, A.V. and Arnold, F.H. Evolution of the C30 carotenoid synthase CrtM for function in a C40 pathway. J. Bacteriol. 184 (2002) 6690–6699. [DOI] [PMID: 12426357]
2.  Pelz, A., Wieland, K.P., Putzbach, K., Hentschel, P., Albert, K. and Gotz, F. Structure and biosynthesis of staphyloxanthin from Staphylococcus aureus. J. Biol. Chem. 280 (2005) 32493–32498. [DOI] [PMID: 16020541]
3.  Ku, B., Jeong, J.C., Mijts, B.N., Schmidt-Dannert, C. and Dordick, J.S. Preparation, characterization, and optimization of an in vitro C30 carotenoid pathway. Appl. Environ. Microbiol. 71 (2005) 6578–6583. [DOI] [PMID: 16269684]
4.  Liu, C.I., Liu, G.Y., Song, Y., Yin, F., Hensler, M.E., Jeng, W.Y., Nizet, V., Wang, A.H. and Oldfield, E. A cholesterol biosynthesis inhibitor blocks Staphylococcus aureus virulence. Science 319 (2008) 1391–1394. [DOI] [PMID: 18276850]
[EC 2.5.1.96 created 2011]
 
 
EC 2.7.1.36     
Accepted name: mevalonate kinase
Reaction: ATP + (R)-mevalonate = ADP + (R)-5-phosphomevalonate
For diagram of terpenoid biosynthesis, click here
Other name(s): mevalonate kinase (phosphorylating); mevalonate phosphokinase; mevalonic acid kinase; mevalonic kinase; mevalonate 5-phosphotransferase ; MVA kinase; ATP:mevalonate 5-phosphotransferase
Systematic name: ATP:(R)-mevalonate 5-phosphotransferase
Comments: CTP, GTP and UTP can also act as donors.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9026-52-2
References:
1.  Hellig, H. and Popják, G. Studies on the biosynthesis of cholesterol. XIII. Phosphomevalonic kinase from liver. J. Lipid Res. 2 (1961) 235–243.
2.  Levy, G.B. and Popják, G. Studies on the biosynthesis of cholesterol. 10. Mevalonic kinase from liver. Biochem. J. 75 (1960) 417–428. [PMID: 14416398]
3.  Markley, K. and Smallman, E. Mevalonic kinase in rabbit liver. Biochim. Biophys. Acta 47 (1961) 327–335.
4.  Tchen, T.T. Mevalonic kinase: purification and properties. J. Biol. Chem. 233 (1958) 1100–1103. [PMID: 13598740]
[EC 2.7.1.36 created 1961]
 
 
EC 2.7.4.2     
Accepted name: phosphomevalonate kinase
Reaction: ATP + (R)-5-phosphomevalonate = ADP + (R)-5-diphosphomevalonate
For diagram of terpenoid biosynthesis, click here
Other name(s): ATP:5-phosphomevalonate phosphotransferase; 5-phosphomevalonate kinase; mevalonate phosphate kinase; mevalonate-5-phosphate kinase; mevalonic acid phosphate kinase
Systematic name: ATP:(R)-5-phosphomevalonate phosphotransferase
Links to other databases: BRENDA, EXPASY, GTD, KEGG, MetaCyc, PDB, CAS registry number: 9026-46-4
References:
1.  Bloch, K., Chaykin, S., Phillips, A.H. and de Waard, A. Mevalonic acid pyrophosphate and isopentenyl pyrophosphate. J. Biol. Chem. 234 (1959) 2595–2604. [PMID: 13801508]
2.  Henning, U., Möslein, E.M. and Lynen, F. Biosynthesis of terpenes. V. Formation of 5-pyrophosphomevalonic acid by phosphomevalonic kinase. Arch. Biochem. Biophys. 83 (1959) 259–267. [DOI] [PMID: 13662013]
3.  Levy, G.B. and Popják, G. Studies on the biosynthesis of cholesterol. 10. Mevalonic kinase from liver. Biochem. J. 75 (1960) 417–428. [PMID: 14416398]
[EC 2.7.4.2 created 1961]
 
 
EC 2.8.2.2     
Accepted name: alcohol sulfotransferase
Reaction: 3′-phosphoadenylyl sulfate + an alcohol = adenosine 3′,5′-bisphosphate + an alkyl sulfate
Glossary: 3′-phosphoadenylyl sulfate = PAPS
Other name(s): hydroxysteroid sulfotransferase; 3β-hydroxy steroid sulfotransferase; Δ5-3β-hydroxysteroid sulfokinase; 3-hydroxysteroid sulfotransferase; HST; 5α-androstenol sulfotransferase; cholesterol sulfotransferase; dehydroepiandrosterone sulfotransferase; estrogen sulfokinase; estrogen sulfotransferase; steroid alcohol sulfotransferase; steroid sulfokinase; steroid sulfotransferase; sterol sulfokinase; sterol sulfotransferase; alcohol/hydroxysteroid sulfotransferase; 3β-hydroxysteroid sulfotransferase; 3′-phosphoadenylyl-sulfate:alcohol sulfotransferase
Systematic name: 3′-phosphoadenylyl-sulfate:alcohol sulfonotransferase
Comments: Primary and secondary alcohols, including aliphatic alcohols, ascorbic acid, chloramphenicol, ephedrine and hydroxysteroids, but not phenolic steroids, can act as acceptors (cf. EC 2.8.2.15 steroid sulfotransferase).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9032-76-2
References:
1.  Lyon, E.S. and Jakoby, W.B. The identity of alcohol sulfotransferases with hydroxysteroid sulfotransferases. Arch. Biochem. Biophys. 202 (1980) 474–481. [DOI] [PMID: 6935986]
2.  Lyon, E.S., Marcus, C.J., Wang, J.-L. and Jakoby, W.B. Hydroxysteroid sulfotransferase. Methods Enzymol. 77 (1981) 206–213. [PMID: 6173569]
[EC 2.8.2.2 created 1961, modified 1980]
 
 
EC 3.1.1.13     
Accepted name: sterol esterase
Reaction: a steryl ester + H2O = a sterol + a fatty acid
Other name(s): cholesterol esterase; cholesteryl ester synthase; triterpenol esterase; cholesteryl esterase; cholesteryl ester hydrolase; sterol ester hydrolase; cholesterol ester hydrolase; cholesterase; acylcholesterol lipase
Systematic name: steryl-ester acylhydrolase
Comments: A group of enzymes of broad specificity, acting on esters of sterols and long-chain fatty acids, that may also bring about the esterification of sterols. Activated by bile salts.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9026-00-0
References:
1.  Hyun, J., Kothari, H., Herm, E., Mortenson, J., Treadwell, C.R. and Vahouny, G.V. Purification and properties of pancreatic juice cholesterol esterase. J. Biol. Chem. 244 (1969) 1937–1945. [PMID: 5780846]
2.  Okawa, Y. and Yamaguchi, T. Studies on sterol-ester hydrolase from Fusarium oxysporum. I. Partial purification and properties. J. Biochem. (Tokyo) 81 (1977) 1209–1215. [PMID: 19426]
3.  Vahouny, G.V. and Tradwell, C.R. Enzymatic synthesis and hydrolysis of cholesterol esters. Methods Biochem. Anal. 16 (1968) 219–272. [PMID: 4877146]
4.  Warnaar, F. Triterpene ester synthesis in latex of Euphorbia species. Phytochemistry 26 (1987) 2715–2721.
[EC 3.1.1.13 created 1961, modified 1990]
 
 
EC 3.2.1.104     
Accepted name: steryl-β-glucosidase
Reaction: cholesteryl-β-D-glucoside + H2O = D-glucose + cholesterol
Systematic name: cholesteryl-β-D-glucoside glucohydrolase
Comments: Acts on glucosides of cholesterol and sitosterol, but not on some related sterols such as coprostanol.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 69494-88-8
References:
1.  Kalinowska, M. and Wojciechowski, Z.A. Purification and some properties of steryl β-D-glucoside hydrolase from Sinapis alba seedlings. Phytochemistry 17 (1978) 1533–1537.
[EC 3.2.1.104 created 1984]
 
 
EC 3.3.2.6     
Accepted name: leukotriene-A4 hydrolase
Reaction: leukotriene A4 + H2O = leukotriene B4
Glossary: leukotriene A4 = (7E,9E,11Z,14Z)-(5S,6S)-5,6-epoxyicosa-7,9,11,14-tetraenoate
leukotriene B4 = (6Z,8E,10E,14Z)-(5S,12R)-5,12-dihydroxyicosa-6,8,10,14-tetraenoate
Other name(s): LTA4 hydrolase; LTA4H; leukotriene A4 hydrolase
Systematic name: (7E,9E,11Z,14Z)-(5S,6S)-5,6-epoxyicosa-7,9,11,14-tetraenoate hydrolase
Comments: This is a bifunctional zinc metalloprotease that displays both epoxide hydrolase and aminopeptidase activities [4,6]. It preferentially cleaves tripeptides at an arginyl bond, with dipeptides and tetrapeptides being poorer substrates [6] (see EC 3.4.11.6, aminopeptidase B). It also converts leukotriene A4 into leukotriene B4, unlike EC 3.3.2.10, soluble epoxide hydrolase, which converts leukotriene A4 into 5,6-dihydroxy-7,9,11,14-icosatetraenoic acid [3,4]. In vertebrates, five epoxide-hydrolase enzymes have been identified to date: EC 3.3.2.6 (leukotriene A4 hydrolase), EC 3.3.2.7 (hepoxilin-epoxide hydrolase), EC 3.3.2.9 (microsomal epoxide hydrolase), EC 3.3.2.10 (soluble epoxide hydrolase) and EC 3.3.2.11 (cholesterol-5,6-oxide hydrolase) [5].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 90119-07-6
References:
1.  Evans, J.F., Dupuis, P. and Ford-Hutchinson, A.W. Purification and characterisation of leukotriene A4 hydrolase from rat neutrophils. Biochim. Biophys. Acta 840 (1985) 43–50. [DOI] [PMID: 3995081]
2.  Minami, M., Ohno, S., Kawasaki, H., Rådmark, O., Samuelsson, B., Jörnvall, H., Shimizu, T., Seyama, Y. and Suzuki, K. Molecular cloning of a cDNA coding for human leukotriene A4 hydrolase - complete primary structure of an enzyme involved in eicosanoid synthesis. J. Biol. Chem. 262 (1987) 13873–13876. [PMID: 3654641]
3.  Haeggström, J., Meijer, J. and Rådmark, O. Leukotriene A4. Enzymatic conversion into 5,6-dihydroxy-7,9,11,14-eicosatetraenoic acid by mouse liver cytosolic epoxide hydrolase. J. Biol. Chem. 261 (1986) 6332–6337. [PMID: 3009453]
4.  Newman, J.W., Morisseau, C. and Hammock, B.D. Epoxide hydrolases: their roles and interactions with lipid metabolism. Prog. Lipid Res. 44 (2005) 1–51. [DOI] [PMID: 15748653]
5.  Fretland, A.J. and Omiecinski, C.J. Epoxide hydrolases: biochemistry and molecular biology. Chem. Biol. Interact. 129 (2000) 41–59. [DOI] [PMID: 11154734]
6.  Orning, L., Gierse, J.K. and Fitzpatrick, F.A. The bifunctional enzyme leukotriene-A4 hydrolase is an arginine aminopeptidase of high efficiency and specificity. J. Biol. Chem. 269 (1994) 11269. [PMID: 8157657]
7.  Ohishi, N., Izumi, T., Minami, M., Kitamura, S., Seyama, Y., Ohkawa, S., Terao, S., Yotsumoto, H., Takaku, F. and Shimizu, T. Leukotriene A4 hydrolase in the human lung. Inactivation of the enzyme with leukotriene A4 isomers. J. Biol. Chem. 262 (1987) 10200–10205. [PMID: 3038871]
[EC 3.3.2.6 created 1989, modified 2006]
 
 
EC 3.3.2.7     
Accepted name: hepoxilin-epoxide hydrolase
Reaction: hepoxilin A3 + H2O = trioxilin A3
Glossary: hepoxilin A3 = (5Z,9E,14Z)-(8ξ,11R,12S)-11,12-epoxy-8-hydroxyicosa-5,9,14-trienoate
trioxilin A3 = (5Z,9E,14Z)-(8ξ,11ξ,12S)-8,11,12-trihydroxyicosa-5,9,14-trienoate
Other name(s): hepoxilin epoxide hydrolase; hepoxylin hydrolase; hepoxilin A3 hydrolase
Systematic name: (5Z,9E,14Z)-(8ξ,11R,12S)-11,12-epoxy-8-hydroxyicosa-5,9,14-trienoate hydrolase
Comments: Converts hepoxilin A3 into trioxilin A3. Highly specific for the substrate, having only slight activity with other epoxides such as leukotriene A4 and styrene oxide [2]. Hepoxilin A3 is an hydroxy-epoxide derivative of arachidonic acid that is formed via the 12-lipoxygenase pathway [2]. It is probable that this enzyme plays a modulatory role in inflammation, vascular physiology, systemic glucose metabolism and neurological function [4]. In vertebrates, five epoxide-hydrolase enzymes have been identified to date: EC 3.3.2.6 (leukotriene-A4 hydrolase), EC 3.3.2.7 (hepoxilin-epoxide hydrolase), EC 3.3.2.9 (microsomal epoxide hydrolase), EC 3.3.2.10 (soluble epoxide hydrolase) and EC 3.3.2.11 (cholesterol 5,6-oxide hydrolase) [3].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 122096-98-4
References:
1.  Pace-Asciak, C.R. Formation and metabolism of hepoxilin A3 by the rat brain. Biochem. Biophys. Res. Commun. 151 (1988) 493–498. [DOI] [PMID: 3348791]
2.  Pace-Asciak, C.R. and Lee, W.-S. Purification of hepoxilin epoxide hydrolase from rat liver. J. Biol. Chem. 264 (1989) 9310–9313. [PMID: 2722835]
3.  Fretland, A.J. and Omiecinski, C.J. Epoxide hydrolases: biochemistry and molecular biology. Chem. Biol. Interact. 129 (2000) 41–59. [DOI] [PMID: 11154734]
4.  Newman, J.W., Morisseau, C. and Hammock, B.D. Epoxide hydrolases: their roles and interactions with lipid metabolism. Prog. Lipid Res. 44 (2005) 1–51. [DOI] [PMID: 15748653]
[EC 3.3.2.7 created 1992, modified 2006]
 
 
EC 3.3.2.9     
Accepted name: microsomal epoxide hydrolase
Reaction: (1) cis-stilbene oxide + H2O = (1R,2R)-1,2-diphenylethane-1,2-diol
(2) 1-(4-methoxyphenyl)-N-methyl-N-[(3-methyloxetan-3-yl)methyl]methanamine + H2O = 2-({[(4-methoxyphenyl)methyl](methyl)amino}methyl)-2-methylpropane-1,3-diol
Glossary: oxirane = ethylene oxide = a 3-membered oxygen-containing ring
oxetane = 1,3-propylene oxide = a 4-membered oxygen-containing ring
Other name(s): microsomal oxirane/oxetane hydrolase; epoxide hydratase (ambiguous); microsomal epoxide hydratase (ambiguous); epoxide hydrase; microsomal epoxide hydrase; arene-oxide hydratase (ambiguous); benzo[a]pyrene-4,5-oxide hydratase; benzo(a)pyrene-4,5-epoxide hydratase; aryl epoxide hydrase (ambiguous); cis-epoxide hydrolase; mEH; EPHX1 (gene name)
Systematic name: cis-stilbene-oxide hydrolase
Comments: This is a key hepatic enzyme that catalyses the hydrolytic ring opening of oxiranes (epoxides) and oxetanes to give the corresponding diols. The enzyme is involved in the metabolism of numerous substrates including the stereoselective hydrolytic ring opening of 7-oxabicyclo[4.1.0]hepta-2,4-dienes (arene oxides) to the corresponding trans-dihydrodiols. The reaction proceeds via a triad mechanism and involves the formation of an hydroxyalkyl-enzyme intermediate. Five epoxide-hydrolase enzymes have been identified in vertebrates to date: EC 3.3.2.6 (leukotriene-A4 hydrolase), EC 3.3.2.7 (hepoxilin-epoxide hydrolase), EC 3.3.2.9 (microsomal epoxide hydrolase), EC 3.3.2.10 (soluble epoxide hydrolase) and EC 3.3.2.11 (cholesterol-5,6-oxide hydrolase).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB
References:
1.  Oesch, F. and Daly, J. Solubilization, purification, and properties of a hepatic epoxide hydrase. Biochim. Biophys. Acta 227 (1971) 692–697. [DOI] [PMID: 4998715]
2.  Jakoby, W.B. and Fjellstedt, T.A. Epoxidases. In: Boyer, P.D. (Ed.), The Enzymes, 3rd edn, vol. 7, Academic Press, New York, 1972, pp. 199–212.
3.  Oesch, F. Mammalian epoxide hydrases: inducible enzymes catalysing the inactivation of carcinogenic and cytotoxic metabolites derived from aromatic and olefinic compounds. Xenobiotica 3 (1973) 305–340. [DOI] [PMID: 4584115]
4.  Oesch, F. Purification and specificity of a human microsomal epoxide hydratase. Biochem. J. 139 (1974) 77–88. [PMID: 4463951]
5.  Lu, A.Y., Ryan, D., Jerina, D.M., Daly, J.W. and Levin, W. Liver microsomal expoxide hydrase. Solubilization, purification, and characterization. J. Biol. Chem. 250 (1975) 8283–8288. [PMID: 240858]
6.  Bellucci, G., Chiappe, C. and Ingrosso, G. Kinetics and stereochemistry of the microsomal epoxide hydrolase-catalyzed hydrolysis of cis-stilbene oxides. Chirality 6 (1994) 577–582. [DOI] [PMID: 7986671]
7.  Fretland, A.J. and Omiecinski, C.J. Epoxide hydrolases: biochemistry and molecular biology. Chem. Biol. Interact. 129 (2000) 41–59. [DOI] [PMID: 11154734]
8.  Morisseau, C. and Hammock, B.D. Epoxide hydrolases: mechanisms, inhibitor designs, and biological roles. Annu. Rev. Pharmacol. Toxicol. 45 (2005) 311–333. [DOI] [PMID: 15822179]
9.  Newman, J.W., Morisseau, C. and Hammock, B.D. Epoxide hydrolases: their roles and interactions with lipid metabolism. Prog. Lipid Res. 44 (2005) 1–51. [DOI] [PMID: 15748653]
10.  Toselli, F., Fredenwall, M., Svensson, P., Li, X.Q., Johansson, A., Weidolf, L. and Hayes, M.A. Oxetane substrates of human microsomal epoxide hydrolase. Drug Metab. Dispos. 45 (2017) 966–973. [DOI] [PMID: 28600384]
[EC 3.3.2.9 created 2006 (EC 3.3.2.3 created 1978, modified 1999, part incorporated 2006), modified 2017]
 
 
EC 3.3.2.10     
Accepted name: soluble epoxide hydrolase
Reaction: an epoxide + H2O = a glycol
Other name(s): epoxide hydrase (ambiguous); epoxide hydratase (ambiguous); arene-oxide hydratase (ambiguous); aryl epoxide hydrase (ambiguous); trans-stilbene oxide hydrolase; sEH; cytosolic epoxide hydrolase
Systematic name: epoxide hydrolase
Comments: Catalyses the hydrolysis of trans-substituted epoxides, such as trans-stilbene oxide, as well as various aliphatic epoxides derived from fatty-acid metabolism [7]. It is involved in the metabolism of arachidonic epoxides (epoxyicosatrienoic acids; EETs) and linoleic acid epoxides. The EETs, which are endogenous chemical mediators, act at the vascular, renal and cardiac levels to regulate blood pressure [4,5]. The enzyme from mammals is a bifunctional enzyme: the C-terminal domain exhibits epoxide-hydrolase activity and the N-terminal domain has the activity of EC 3.1.3.76, lipid-phosphate phosphatase [1,2]. Like EC 3.3.2.9, microsomal epoxide hydrolase, it is probable that the reaction involves the formation of an hydroxyalkyl—enzyme intermediate [4,6]. The enzyme can also use leukotriene A4, the substrate of EC 3.3.2.6, leukotriene-A4 hydrolase, but it forms 5,6-dihydroxy-7,9,11,14-icosatetraenoic acid rather than leukotriene B4 as the product [9,10]. In vertebrates, five epoxide-hydrolase enzymes have been identified to date: EC 3.3.2.6 (leukotriene-A4 hydrolase), EC 3.3.2.7 (hepoxilin-epoxide hydrolase), EC 3.3.2.9 (microsomal epoxide hydrolase), EC 3.3.2.10 (soluble epoxide hydrolase) and EC 3.3.2.11 (cholesterol 5,6-oxide hydrolase) [7].
Links to other databases: BRENDA, EAWAG-BBD, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9048-63-9
References:
1.  Newman, J.W., Morisseau, C., Harris, T.R. and Hammock, B.D. The soluble epoxide hydrolase encoded by EPXH2 is a bifunctional enzyme with novel lipid phosphate phosphatase activity. Proc. Natl. Acad. Sci. USA 100 (2003) 1558–1563. [DOI] [PMID: 12574510]
2.  Cronin, A., Mowbray, S., Dürk, H., Homburg, S., Fleming, I., Fisslthaler, B., Oesch, F. and Arand, M. The N-terminal domain of mammalian soluble epoxide hydrolase is a phosphatase. Proc. Natl. Acad. Sci. USA 100 (2003) 1552–1557. [DOI] [PMID: 12574508]
3.  Oesch, F. Mammalian epoxide hydrases: inducible enzymes catalysing the inactivation of carcinogenic and cytotoxic metabolites derived from aromatic and olefinic compounds. Xenobiotica 3 (1973) 305–340. [DOI] [PMID: 4584115]
4.  Morisseau, C. and Hammock, B.D. Epoxide hydrolases: mechanisms, inhibitor designs, and biological roles. Annu. Rev. Pharmacol. Toxicol. 45 (2005) 311–333. [DOI] [PMID: 15822179]
5.  Yu, Z., Xu, F., Huse, L.M., Morisseau, C., Draper, A.J., Newman, J.W., Parker, C., Graham, L., Engler, M.M., Hammock, B.D., Zeldin, D.C. and Kroetz, D.L. Soluble epoxide hydrolase regulates hydrolysis of vasoactive epoxyeicosatrienoic acids. Circ. Res. 87 (2000) 992–998. [PMID: 11090543]
6.  Lacourciere, G.M. and Armstrong, R.N. The catalytic mechanism of microsomal epoxide hydrolase involves an ester intermediate. J. Am. Chem. Soc. 115 (1993) 10466.
7.  Fretland, A.J. and Omiecinski, C.J. Epoxide hydrolases: biochemistry and molecular biology. Chem. Biol. Interact. 129 (2000) 41–59. [DOI] [PMID: 11154734]
8.  Zeldin, D.C., Wei, S., Falck, J.R., Hammock, B.D., Snapper, J.R. and Capdevila, J.H. Metabolism of epoxyeicosatrienoic acids by cytosolic epoxide hydrolase: substrate structural determinants of asymmetric catalysis. Arch. Biochem. Biophys. 316 (1995) 443–451. [DOI] [PMID: 7840649]
9.  Haeggström, J., Meijer, J. and Rådmark, O. Leukotriene A4. Enzymatic conversion into 5,6-dihydroxy-7,9,11,14-eicosatetraenoic acid by mouse liver cytosolic epoxide hydrolase. J. Biol. Chem. 261 (1986) 6332–6337. [PMID: 3009453]
10.  Newman, J.W., Morisseau, C. and Hammock, B.D. Epoxide hydrolases: their roles and interactions with lipid metabolism. Prog. Lipid Res. 44 (2005) 1–51. [DOI] [PMID: 15748653]
[EC 3.3.2.10 created 2006 (EC 3.3.2.3 created 1978, part incorporated 2006)]
 
 
EC 3.3.2.11     
Accepted name: cholesterol-5,6-oxide hydrolase
Reaction: (1) 5,6α-epoxy-5α-cholestan-3β-ol + H2O = 5α-cholestane-3β,5α,6β-triol
(2) 5,6β-epoxy-5β-cholestan-3β-ol + H2O = 5α-cholestane-3β,5α,6β-triol
For diagram of reactions, click here
Glossary: cholesterol = cholest-5-en-3β-ol
Other name(s): cholesterol-epoxide hydrolase; ChEH
Systematic name: 5,6α-epoxy-5α-cholestan-3β-ol hydrolase
Comments: The enzyme appears to work equally well with either epoxide as substrate [3]. The product is a competitive inhibitor of the reaction. In vertebrates, five epoxide-hydrolase enzymes have been identified to date: EC 3.3.2.6 (leukotriene-A4 hydrolase), EC 3.3.2.7 (hepoxilin-epoxide hydrolase), EC 3.3.2.9 (microsomal epoxide hydrolase), EC 3.3.2.10 (soluble epoxide hydrolase) and EC 3.3.2.11 (cholesterol 5,6-oxide hydrolase) [3].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB
References:
1.  Levin, W., Michaud, D.P., Thomas, P.E. and Jerina, D.M. Distinct rat hepatic microsomal epoxide hydrolases catalyze the hydration of cholesterol 5,6 α-oxide and certain xenobiotic alkene and arene oxides. Arch. Biochem. Biophys. 220 (1983) 485–494. [DOI] [PMID: 6401984]
2.  Oesch, F., Timms, C.W., Walker, C.H., Guenthner, T.M., Sparrow, A., Watabe, T. and Wolf, C.R. Existence of multiple forms of microsomal epoxide hydrolases with radically different substrate specificities. Carcinogenesis 5 (1984) 7–9. [DOI] [PMID: 6690087]
3.  Sevanian, A. and McLeod, L.L. Catalytic properties and inhibition of hepatic cholesterol-epoxide hydrolase. J. Biol. Chem. 261 (1986) 54–59. [PMID: 3941086]
4.  Fretland, A.J. and Omiecinski, C.J. Epoxide hydrolases: biochemistry and molecular biology. Chem. Biol. Interact. 129 (2000) 41–59. [DOI] [PMID: 11154734]
5.  Newman, J.W., Morisseau, C. and Hammock, B.D. Epoxide hydrolases: their roles and interactions with lipid metabolism. Prog. Lipid Res. 44 (2005) 1–51. [DOI] [PMID: 15748653]
[EC 3.3.2.11 created 2006]
 
 
EC 3.4.21.70     
Accepted name: pancreatic endopeptidase E
Reaction: Preferential cleavage: Ala┼. Does not hydrolyse elastin
Other name(s): cholesterol-binding proteinase; proteinase E; cholesterol-binding serine proteinase; pancreatic protease E; pancreatic proteinase E; cholesterol-binding pancreatic proteinase; CBPP; pancreas E proteinase
Comments: A peptidase of family S1 (trypsin family) from pancreatic juice. Unlike elastases, has an acidic pI. Binds cholesterol
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, MEROPS, CAS registry number: 68073-27-8
References:
1.  Mallory, P.A. and Travis, J. Human pancreatic enzymes: purification and characterization of a nonelastolytic enzyme, protease E, resembling elastase. Biochemistry 14 (1975) 722–729. [PMID: 234742]
2.  Shen, W., Fletcher, T.S. and Largman, C. Primary structure of human pancreatic protease E determined by sequence analysis of the cloned mRNA. Biochemistry 26 (1987) 3447–3452. [PMID: 3477287]
[EC 3.4.21.70 created 1992]
 
 
EC 3.4.21.112     
Accepted name: site-1 protease
Reaction: Processes precursors containing basic and hydrophobic/aliphatic residues at P4 and P2, respectively, with a relatively relaxed acceptance of amino acids at P1 and P3
Other name(s): mammalian subtilisin/kexin isozyme 1; membrane-bound transcription factor site-1 protease; proprotein convertase SKI-1; proprotein convertase SKI-1/S1PPS1; S1P endopeptidase; S1P protease; site-1 peptidase; site-1 protease; SKI-1; SREBP proteinase; SREBP S1 protease; SREBP-1 proteinase; SREBP-2 proteinase; sterol regulatory element-binding protein proteinase; sterol regulatory element-binding protein site 1 protease; sterol-regulated luminal protease; subtilase SKI-1; subtilase SKI-1/S1P; subtilisin/kexin-isozyme 1
Comments: Cleaves sterol regulatory element-binding proteins (SREBPs) and thereby initiates a process by which the active fragments of the SREBPs translocate to the nucleus and activate genes controlling the synthesis and uptake of cholesterol and unsaturated fatty acids into the bloodstream [1]. The enzyme also processes pro-brain-derived neurotrophic factor and undergoes autocatalytic activation in the endoplasmic reticulum through sequential cleavages [5]. The enzyme can also process the unfolded protein response stress factor ATF6 at an Arg-His-Lys-Lys┼ site [4,8], and the envelope glycoprotein of the highly infectious Lassa virus [5,8] and Crimean Congo hemorrhagic fever virus at Arg-Arg-Lys-Lys┼ [7,8]. Belongs in peptidase family S8A.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 167140-48-9
References:
1.  Espenshade, P.J., Cheng, D., Goldstein, J.L. and Brown, M.S. Autocatalytic processing of site-1 protease removes propeptide and permits cleavage of sterol regulatory element-binding proteins. J. Biol. Chem. 274 (1999) 22795–22804. [DOI] [PMID: 10428864]
2.  Cheng, D., Espenshade, P.J., Slaughter, C.A., Jaen, J.C., Brown, M.S. and Goldstein, J.L. Secreted site-1 protease cleaves peptides corresponding to luminal loop of sterol regulatory element-binding proteins. J. Biol. Chem. 274 (1999) 22805–22812. [DOI] [PMID: 10428865]
3.  Touré, B.B., Munzer, J.S., Basak, A., Benjannet, S., Rochemont, J., Lazure, C., Chrétien, M. and Seidah, N.G. Biosynthesis and enzymatic characterization of human SKI-1/S1P and the processing of its inhibitory prosegment. J. Biol. Chem. 275 (2000) 2349–2358. [DOI] [PMID: 10644685]
4.  Ye, J., Rawson, R.B., Komuro, R., Chen, X., Dave, U.P., Prywes, R., Brown, M.S. and Goldstein, J.L. ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs. Mol. Cell 6 (2000) 1355–1364. [DOI] [PMID: 11163209]
5.  Lenz, O., ter Meulen, J., Klenk, H.D., Seidah, N.G. and Garten, W. The Lassa virus glycoprotein precursor GP-C is proteolytically processed by subtilase SKI-1/S1P. Proc. Natl. Acad. Sci. USA 98 (2001) 12701–12705. [DOI] [PMID: 11606739]
6.  Basak, A., Chrétien, M. and Seidah, N.G. A rapid fluorometric assay for the proteolytic activity of SKI-1/S1P based on the surface glycoprotein of the hemorrhagic fever Lassa virus. FEBS Lett. 514 (2002) 333–339. [DOI] [PMID: 11943176]
7.  Vincent, M.J., Sanchez, A.J., Erickson, B.R., Basak, A., Chretien, M., Seidah, N.G. and Nichol, S.T. Crimean-Congo hemorrhagic fever virus glycoprotein proteolytic processing by subtilase SKI-1. J. Virol. 77 (2003) 8640–8649. [DOI] [PMID: 12885882]
8.  Seidah, N.G. and Chrétien, M. Proprotein convertase SKI-1/S1P. In: Barrett, A.J., Rawlings, N.D. and Woessner, J.F. (Ed.), Handbook of Proteolytic Enzymes, 2nd edn, vol. 2, Elsevier, London, 2004, pp. 1845–1847.
[EC 3.4.21.112 created 2006]
 
 
EC 3.7.1.17     
Accepted name: 4,5:9,10-diseco-3-hydroxy-5,9,17-trioxoandrosta-1(10),2-diene-4-oate hydrolase
Reaction: (1E,2Z)-3-hydroxy-5,9,17-trioxo-4,5:9,10-disecoandrosta-1(10),2-dien-4-oate + H2O = 3-[(3aS,4S,7aS)-7a-methyl-1,5-dioxo-octahydro-1H-inden-4-yl]propanoate + (2Z,4Z)-2-hydroxyhexa-2,4-dienoate
Other name(s): tesD (gene name); hsaD (gene name)
Systematic name: 4,5:9,10-diseco-3-hydroxy-5,9,17-trioxoandrosta-1(10),2-diene-4-oate hydrolase ( (2Z,4Z)-2-hydroxyhexa-2,4-dienoate-forming)
Comments: The enzyme is involved in the bacterial degradation of the steroid ring structure, and is involved in degradation of multiple steroids, such as testosterone [1], cholesterol [2], and sitosterol.
Links to other databases: BRENDA, EAWAG-BBD, EXPASY, KEGG, MetaCyc, PDB
References:
1.  Horinouchi, M., Hayashi, T., Koshino, H., Kurita, T. and Kudo, T. Identification of 9,17-dioxo-1,2,3,4,10,19-hexanorandrostan-5-oic acid, 4-hydroxy-2-oxohexanoic acid, and 2-hydroxyhexa-2,4-dienoic acid and related enzymes involved in testosterone degradation in Comamonas testosteroni TA441. Appl. Environ. Microbiol. 71 (2005) 5275–5281. [DOI] [PMID: 16151114]
2.  Van der Geize, R., Yam, K., Heuser, T., Wilbrink, M.H., Hara, H., Anderton, M.C., Sim, E., Dijkhuizen, L., Davies, J.E., Mohn, W.W. and Eltis, L.D. A gene cluster encoding cholesterol catabolism in a soil actinomycete provides insight into Mycobacterium tuberculosis survival in macrophages. Proc. Natl. Acad. Sci. USA 104 (2007) 1947–1952. [DOI] [PMID: 17264217]
3.  Lack, N., Lowe, E.D., Liu, J., Eltis, L.D., Noble, M.E., Sim, E. and Westwood, I.M. Structure of HsaD, a steroid-degrading hydrolase, from Mycobacterium tuberculosis. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 64 (2008) 2–7. [DOI] [PMID: 18097091]
4.  Lack, N.A., Yam, K.C., Lowe, E.D., Horsman, G.P., Owen, R.L., Sim, E. and Eltis, L.D. Characterization of a carbon-carbon hydrolase from Mycobacterium tuberculosis involved in cholesterol metabolism. J. Biol. Chem. 285 (2010) 434–443. [DOI] [PMID: 19875455]
[EC 3.7.1.17 created 2012]
 
 
EC 4.1.2.33     
Accepted name: fucosterol-epoxide lyase
Reaction: (24R,241R)-fucosterol epoxide = desmosterol + acetaldehyde
Glossary: (24R,241R)-fucosterol epoxide = (3β,24R,28R)-24,28-epoxystigmast-5-en-3-ol
Other name(s): (24R,24′R)-fucosterol-epoxide acetaldehyde-lyase; (24R,24′R)-fucosterol-epoxide acetaldehyde-lyase (desmosterol-forming)
Systematic name: (24R,241R)-fucosterol-epoxide acetaldehyde-lyase (desmosterol-forming)
Comments: The insect enzyme is involved in the conversion of sitosterol into cholesterol.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 99676-42-3
References:
1.  Prestwich, G.D., Angelastro, M., De Palma, A. and Perino, M.A. Fucosterol epoxide lyase of insects: synthesis of labeled substrates and development of a partition assay. Anal. Biochem. 151 (1985) 315–326. [DOI] [PMID: 3913328]
[EC 4.1.2.33 created 1989, modified 2013]
 
 
EC 4.2.1.107     
Accepted name: 3α,7α,12α-trihydroxy-5β-cholest-24-enoyl-CoA hydratase
Reaction: (24R,25R)-3α,7α,12α,24-tetrahydroxy-5β-cholestanoyl-CoA = (24E)-3α,7α,12α-trihydroxy-5β-cholest-24-enoyl-CoA + H2O
For diagram of cholic-acid biosynthesis (sidechain), click here
Other name(s): 46 kDa hydratase 2; (24R,25R)-3α,7α,12α,24-tetrahydroxy-5β-cholestanoyl-CoA hydro-lyase
Systematic name: (24R,25R)-3α,7α,12α,24-tetrahydroxy-5β-cholestanoyl-CoA hydro-lyase [(24E)-3α,7α,12α-trihydroxy-5β-cholest-24-enoyl-CoA-forming]
Comments: This enzyme forms part of the rat peroxisomal multifunctional enzyme perMFE-2, which also exhibits a dehydrogenase activity. The enzyme is involved in the β-oxidation of the cholesterol side chain in the cholic-acid-biosynthesis pathway.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 152787-68-3
References:
1.  Qin, Y.M., Haapalainen, A.M., Conry, D., Cuebas, D.A., Hiltunen, J.K. and Novikov, D.K. Recombinant 2-enoyl-CoA hydratase derived from rat peroxisomal multifunctional enzyme 2: role of the hydratase reaction in bile acid synthesis. Biochem. J. 328 (1997) 377–382. [PMID: 9371691]
2.  Xu, R. and Cuebas, D.A. The reactions catalyzed by the inducible bifunctional enzyme of rat liver peroxisomes cannot lead to the formation of bile acids. Biochem. Biophys. Res. Commun. 221 (1996) 271–278. [DOI] [PMID: 8619845]
3.  Kinoshita, T., Miyata, M., Ismail, S.M., Fujimoto, Y., Kakinuma, K., Kokawa, N.I. and Morisaki, M. Synthesis and determination of stereochemistry of four diastereoisomers at the C-24 and C-25 positions of 3α,7α,12α,24-tetrahydroxy-5β-cholestan-26-oic acid and cholic acid. Chem. Pharm. Bull. 36 (1988) 134–141.
4.  Fujimoto, Y., Kinoshita, T., Oya, I., Kakinuma, K., Ismail, S.M., Sonoda, Y., Sato, Y. and Morisaki, M. Non-stereoselective conversion of the four diastereoisomers at the C-24 and C-25 positions of 3α,7α,12α,24-tetrahydroxy-5β-cholestan-26-oic acid and cholic acid. Chem. Pharm. Bull. 36 (1988) 142–145.
5.  Kurosawa, T., Sato, M., Nakano, H., Fujiwara, M., Murai, T., Yoshimura, T. and Hashimoto, T. Conjugation reactions catalyzed by bifunctional proteins related to β-oxidation in bile acid biosynthesis. Steroids 66 (2001) 107–114. [DOI] [PMID: 11146090]
6.  Russell, D.W. The enzymes, regulation, and genetics of bile acid synthesis. Annu. Rev. Biochem. 72 (2003) 137–174. [DOI] [PMID: 12543708]
[EC 4.2.1.107 created 2005]
 
 
EC 5.3.3.1     
Accepted name: steroid Δ-isomerase
Reaction: a 3-oxo-Δ5-steroid = a 3-oxo-Δ4-steroid
For diagram of cholesterol catabolism (rings A, B and C), click here
Other name(s): hydroxysteroid isomerase; steroid isomerase; Δ5-ketosteroid isomerase; Δ5(or Δ4)-3-keto steroid isomerase; Δ5-steroid isomerase; 3-oxosteroid isomerase; Δ5-3-keto steroid isomerase; Δ5-3-oxosteroid isomerase
Systematic name: 3-oxosteroid Δ5-Δ4-isomerase
Comments: This activity is catalysed by several distinct enzymes (cf. EC 1.1.3.6, cholesterol oxidase and EC 1.1.1.145, 3-hydroxy-5-steroid dehydrogenase).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9031-36-1
References:
1.  Ewald, W., Werbein, H. and Chaikoff, I.L. Evidence for the presence of 17-hydroxypregnenedione isomerase in beef adrenal cortex. Biochim. Biophys. Acta 111 (1965) 306–312. [DOI] [PMID: 5867327]
2.  Kawahara, F.S. and Talalay, P. Crystalline Δ5-3-ketosteroid isomerase. J. Biol. Chem. 235 (1960) PC1–PC2. [PMID: 14404954]
3.  Talalay, P. and Wang, V.S. Enzymic isomerization of Δ5-3-ketosteroids. Biochim. Biophys. Acta 18 (1955) 300–301. [PMID: 13276386]
4.  MacLachlan, J., Wotherspoon, A.T., Ansell, R.O. and Brooks, C.J. Cholesterol oxidase: sources, physical properties and analytical applications. J. Steroid Biochem. Mol. Biol. 72 (2000) 169–195. [DOI] [PMID: 10822008]
[EC 5.3.3.1 created 1961]
 
 
EC 5.3.3.5     
Accepted name: cholestenol Δ-isomerase
Reaction: 5α-cholest-7-en-3β-ol = 5α-cholest-8-en-3β-ol
For diagram of the modification of sterol rings B, C and D, click here
Systematic name: Δ7-cholestenol Δ7-Δ8-isomerase
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 52410-46-5
References:
1.  Wilton, D.C., Rahimtula, A.D. and Akhtar, M. The reversibility of the Δ8-cholestenol-Δ7-cholestenol isomerase reaction in cholesterol biosynthesis. Biochem. J. 114 (1969) 71–73. [PMID: 5810070]
[EC 5.3.3.5 created 1972]
 
 
EC 6.2.1.41     
Accepted name: 3-[(3aS,4S,7aS)-7a-methyl-1,5-dioxo-octahydro-1H-inden-4-yl]propanoate—CoA ligase
Reaction: ATP + 3-[(3aS,4S,7aS)-7a-methyl-1,5-dioxo-octahydro-1H-inden-4-yl]propanoate + CoA = AMP + diphosphate + 3-[(3aS,4S,7aS)-7a-methyl-1,5-dioxo-octahydro-1H-inden-4-yl]propanoyl-CoA
For diagram of cholesterol catabolism, click here
Glossary: 3-[(3aS,4S,7aS)-7a-methyl-1,5-dioxo-octahydro-1H-inden-4-yl]propanoate = HIP
Other name(s): fadD3 (gene name); HIP—CoA ligase
Systematic name: 3-[(3aS,4S,7aS)-7a-methyl-1,5-dioxo-octahydro-1H-inden-4-yl]propanoate:CoA ligase (AMP-forming)
Comments: The enzyme, characterized from actinobacterium Mycobacterium tuberculosis, catalyses a step in the degradation of cholesterol and cholate. The enzyme is very specific for its substrate, and requires that the side chain at C17 is completely removed.
Links to other databases: BRENDA, EAWAG-BBD, EXPASY, KEGG, MetaCyc
References:
1.  Horinouchi, M., Hayashi, T., Koshino, H. and Kudo, T. ORF18-disrupted mutant of Comamonas testosteroni TA441 accumulates significant amounts of 9,17-dioxo-1,2,3,4,10,19-hexanorandrostan-5-oic acid and its derivatives after incubation with steroids. J. Steroid Biochem. Mol. Biol. 101 (2006) 78–84. [DOI] [PMID: 16891113]
2.  Casabon, I., Crowe, A.M., Liu, J. and Eltis, L.D. FadD3 is an acyl-CoA synthetase that initiates catabolism of cholesterol rings C and D in actinobacteria. Mol. Microbiol. 87 (2013) 269–283. [DOI] [PMID: 23146019]
[EC 6.2.1.41 created 2014]
 
 
EC 6.2.1.42     
Accepted name: 3-oxocholest-4-en-26-oate—CoA ligase
Reaction: ATP + (25S)-3-oxocholest-4-en-26-oate + CoA = AMP + diphosphate + (25S)-3-oxocholest-4-en-26-oyl-CoA
For diagram of cholic acid biosynthesis (sidechain), click here
Other name(s): fadD19 (gene name)
Systematic name: (25S)-3-oxocholest-4-en-26-oate:CoA ligase (AMP-forming)
Comments: The enzyme, characterized from actinobacterium Mycobacterium tuberculosis, catalyses a step in the degradation of cholesterol. It is responsible for the activation of the C8 side chain. 3β-hydroxycholest-5-en-26-oate can also be used as substrate.
Links to other databases: BRENDA, EAWAG-BBD, EXPASY, KEGG, MetaCyc
References:
1.  Wilbrink, M.H., Petrusma, M., Dijkhuizen, L. and van der Geize, R. FadD19 of Rhodococcus rhodochrous DSM43269, a steroid-coenzyme A ligase essential for degradation of C-24 branched sterol side chains. Appl. Environ. Microbiol. 77 (2011) 4455–4464. [DOI] [PMID: 21602385]
2.  Casabon, I., Swain, K., Crowe, A.M., Eltis, L.D. and Mohn, W.W. Actinobacterial acyl coenzyme a synthetases involved in steroid side-chain catabolism. J. Bacteriol. 196 (2014) 579–587. [DOI] [PMID: 24244004]
[EC 6.2.1.42 created 2014]
 
 


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