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Literature summary for 1.3.1.72 extracted from
- Cholesterol biosynthesis from lanosterol: development of a novel assay method and characterization of rat liver microsomal lanosterol DELTA24-reductase (1997), Biochem. J., 326, 609-616.
Activating Compound
| Activating Compound | Comment | Organism | Structure |
|---|---|---|---|
| cholestyramine | 120fold induction and activation by feeding 5% cholestyramine plus 0.1% lovastatin, CL-diet, and by modulating diurnal variation | Rattus norvegicus |  |
| CO | substrate lanosterol: required to inhibit 14alpha-methyl demethylase, 14alpha-demethylation of lanosterol. 14alpha-methyl demethylase activity is dominant over 24-reductase activity, and blockade or removal of 14alpha-methyl demethylase activity is absolutely required for the detection of maximal 24-reductase activity when lanosterol substrate is present. 24-reductase activity is activated in time-dependent manner when 14alpha-methyl demethylase is blocked by CO treatment | Rattus norvegicus | |
| ketoconazole | substrate lanosterol: dose-dependent activation, less effective than miconazole, required to inhibit 14alpha-methyl demethylase, 14alpha-demethylation of lanosterol. 14alpha-methyl demethylase activity is dominant over 24-reductase activity, and blockade or removal of 14alpha-methyl demethylase activity is absolutely required for the detection of maximal 24-reductase activity when lanosterol substrate is present | Rattus norvegicus | |
| lovastatin | 120fold induction and activation by feeding 5% cholestyramine plus 0.1% lovastatin, CL-diet, and by modulating diurnal variation | Rattus norvegicus | |
| miconazole | substrate lanosterol: dose-dependent activation, maximum activation with about 0.01 mM miconazole, required to inhibit 14alpha-methyl demethylase, 14alpha-demethylation of lanosterol. 14alpha-methyl demethylase activity is dominant over 24-reductase activity, and blockade or removal of 14alpha-methyl demethylase activity is absolutely required for the detection of maximal 24-reductase activity when lanosterol substrate is present | Rattus norvegicus | |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| 3-beta-(2-(diethylamino)ethoxy)androst-5-en-17-one | U18666A, non-competitive inhibition, Ki: 0.000157 mM, IC50 about 0.00015 mM, 690fold higher affinity for the enzyme than substrate lanosterol | Rattus norvegicus | |
| additional information | no inhibition by lovastatin, mevalonolactone, Squalestatin 1, (E)-N-ethyl-N-(6,6-dimethyl-2-hepten-4-ynyl)-3-((3,3'-bithiophen-5-yl)methoxy)benzenemethanamine, NB-598, trans-1,4-bis(2-chlorobenzylaminomethyl)cyclohexane dihydrochloride, AY-9944 and CN- ion | Rattus norvegicus | |
| Triparanol | 4-chloro-alpha-[4-[2-diethylaminoethoxy]phenyl]-alpha-(4-methylphenyl)benze-methanol; non-competitive inhibition, specific inhibitor, Ki: 0.000523 mM, IC50 about 0.0008 mM, 208fold higher affinity for the enzyme than substrate lanosterol | Rattus norvegicus | |
KM Value [mM]
| KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| additional information | - |
additional information | kinetic behaviour and kinetic data | Rattus norvegicus | |
| 0.037 | - |
5alpha-cholesta-7,24-dien-3beta-ol | - |
Rattus norvegicus | |
| 0.109 | - |
4,4',14alpha-trimethyl-5alpha-cholesta-8,24-dien-3beta-ol | lanosterol | Rattus norvegicus | |
| 0.163 | - |
5alpha-cholesta-5,24-dien-3beta-ol | desmosterol | Rattus norvegicus | |
| 0.176 | - |
5alpha-cholesta-8,24-dien-3beta-ol | zymosterol | Rattus norvegicus | |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| membrane | membrane-bound | Rattus norvegicus | 16020 | - |
| microsome | microsome-bound | Rattus norvegicus | - |
- |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| 5alpha-cholesta-7,24-dien-3beta-ol + NADPH | Rattus norvegicus | C-24 reduction of sterols probably takes place straight after sterol DELTA8-7 isomerization of zymosterol, which occurs several steps after C-32 demethylation of lanosterol in the 19-step pathway of cholesterol biosynthesis from lanosterol | 5alpha-cholesta-7-en-3beta-ol + NADP+ | - |
? | |
| 5alpha-cholesta-7,24-dien-3beta-ol + NADPH | Rattus norvegicus | C-24 reduction of DELTA7,24-diene | 5alpha-cholesta-7-en-3beta-ol + NADP+ | - |
? | |
| 5alpha-cholesta-7,24-dien-3beta-ol + NADPH | Rattus norvegicus | most reactive, probably natural substrate | 5alpha-cholesta-7-en-3beta-ol + NADP+ | - |
? | |
| additional information | Rattus norvegicus | anaerobic reduction of 24(25)-enes of lanosterol and other obligatory intermediates of cholesterol biosynthesis from lanosterol in mammals to produce 24(25)-dihydrosterols | ? | - |
? | |
| additional information | Rattus norvegicus | C-24 reduction of sterols probably takes place straight after sterol DELTA8-7 isomerization of zymosterol, which occurs several steps after C-32 demethylation of lanosterol in the 19-step pathway of cholesterol biosynthesis from lanosterol | ? | - |
? | |
| additional information | Rattus norvegicus | cholesterogenic enzyme | ? | - |
? | |
| additional information | Rattus norvegicus | important enzyme in the 19-step pathway of cholesterol biosynthesis from lanosterol | ? | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Rattus norvegicus | - |
male sprague-dawley rats | - |
Reaction
| Reaction | Comment | Organism | Reaction ID |
|---|---|---|---|
| 5alpha-cholest-7-en-3beta-ol + NADP+ = 5alpha-cholesta-7,24-dien-3beta-ol + NADPH + H+ | anaerobic reduction of 24(25)-enes of lanosterol and other obligatory intermediates of cholesterol biosynthesis from lanosterol | Rattus norvegicus | |
| 5alpha-cholest-7-en-3beta-ol + NADP+ = 5alpha-cholesta-7,24-dien-3beta-ol + NADPH + H+ | regulation, enzyme induction, dietary induction | Rattus norvegicus |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| hepatocyte | - |
Rattus norvegicus | - |
| liver | - |
Rattus norvegicus | - |
Specific Activity [micromol/min/mg]
| Specific Activity Minimum [µmol/min/mg] | Specific Activity Maximum [µmol/min/mg] | Comment | Organism |
|---|---|---|---|
| additional information | - |
- |
Rattus norvegicus |
| 0.0015 | - |
substrate: 5alpha-cholesta-7,24-dien-3beta-ol | Rattus norvegicus |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| 4,4-dimethyl-5alpha-cholesta-8,24-dien-3beta-ol + NADPH | - |
Rattus norvegicus | 4,4-dimethyl-5alpha-cholesta-8-en-3beta-ol + NADP+ | - |
? | |
| 5alpha-cholesta-7,24-dien-3beta-ol + NADPH | most reactive, best substrate, 17.8fold activity compared with lanosterol, 4,4',14alpha-trimethyl-5alpha-cholesta-8,24-dien-3beta-ol | Rattus norvegicus | 5alpha-cholesta-7-en-3beta-ol + NADP+ | lathosterol | ? | |
| 5alpha-cholesta-7,24-dien-3beta-ol + NADPH | C-24 reduction of sterols probably takes place straight after sterol DELTA8-7 isomerization of zymosterol, which occurs several steps after C-32 demethylation of lanosterol in the 19-step pathway of cholesterol biosynthesis from lanosterol | Rattus norvegicus | 5alpha-cholesta-7-en-3beta-ol + NADP+ | - |
? | |
| 5alpha-cholesta-7,24-dien-3beta-ol + NADPH | C-24 reduction of DELTA7,24-diene | Rattus norvegicus | 5alpha-cholesta-7-en-3beta-ol + NADP+ | - |
? | |
| 5alpha-cholesta-7,24-dien-3beta-ol + NADPH | most reactive, probably natural substrate | Rattus norvegicus | 5alpha-cholesta-7-en-3beta-ol + NADP+ | - |
? | |
| cholesta-5,7,24-trien-3beta-ol + NADPH + H+ | - |
Rattus norvegicus | cholesta-5,7-dien-3beta-ol + NADP+ | - |
? | |
| desmosterol + NADPH | 5.5fold activity compared with lanosterol, 4,4',14alpha-trimethyl-5alpha-cholesta-8,24-dien-3beta-ol | Rattus norvegicus | cholesterol + NADP+ | - |
? | |
| desmosterol + NADPH | 5alpha-cholesta-5,24-dien-3beta-ol | Rattus norvegicus | cholesterol + NADP+ | - |
? | |
| lanosterol + NADPH | 14alpha-methyl demethylase activity is dominant over 24-reductase activity, and blockade or removal of 14alpha-methyl demethylase activity is absolutely required for the detection of maximal 24-reductase activity when lanosterol substrate is present | Rattus norvegicus | 4,4,14alpha-trimethyl-5alpha-cholesta-8-en-3beta-ol + NADP+ | - |
? | |
| lanosterol + NADPH | 4,4',14alpha-trimethyl-5alpha-cholesta-8,24-dien-3beta-ol | Rattus norvegicus | 4,4,14alpha-trimethyl-5alpha-cholesta-8-en-3beta-ol + NADP+ | - |
? | |
| additional information | substrate specificity | Rattus norvegicus | ? | - |
? | |
| additional information | anaerobic reduction of 24(25)-enes of lanosterol and other obligatory intermediates of cholesterol biosynthesis from lanosterol in mammals to produce 24(25)-dihydrosterols | Rattus norvegicus | ? | - |
? | |
| additional information | C-24 reduction of sterols probably takes place straight after sterol DELTA8-7 isomerization of zymosterol, which occurs several steps after C-32 demethylation of lanosterol in the 19-step pathway of cholesterol biosynthesis from lanosterol | Rattus norvegicus | ? | - |
? | |
| additional information | substrate specificity studies | Rattus norvegicus | ? | - |
? | |
| additional information | cholesterogenic enzyme | Rattus norvegicus | ? | - |
? | |
| additional information | important enzyme in the 19-step pathway of cholesterol biosynthesis from lanosterol | Rattus norvegicus | ? | - |
? | |
| zymosterol + NADPH | 6.1fold activity compared with lanosterol, 4,4',14alpha-trimethyl-5alpha-cholesta-8,24-dien-3beta-ol | Rattus norvegicus | 5alpha-cholesta-8-en-3beta-ol + NADP+ | - |
? | |
| zymosterol + NADPH | 5alpha-cholesta-8,24-dien-3beta-ol | Rattus norvegicus | 5alpha-cholesta-8-en-3beta-ol + NADP+ | - |
? | |
Temperature Optimum [°C]
| Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
|---|---|---|---|
| 37 | - |
assay at, anaerobically | Rattus norvegicus |
pH Optimum
| pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|
| 6.2 | - |
assay at, anaerobically | Rattus norvegicus |
| 6.5 | - |
- |
Rattus norvegicus |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| NADPH | - |
Rattus norvegicus | |
Ki Value [mM]
| Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 0.000157 | - |
3-beta-(2-(diethylamino)ethoxy)androst-5-en-17-one | - |
Rattus norvegicus | |
| 0.000523 | - |
Triparanol | - |
Rattus norvegicus | |
IC50 Value
| IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
|---|---|---|---|---|---|
| 0.00015 | - |
U18666A, non-competitive inhibition, Ki: 0.000157 mM, IC50 about 0.00015 mM, 690fold higher affinity for the enzyme than substrate lanosterol | Rattus norvegicus | 3-beta-(2-(diethylamino)ethoxy)androst-5-en-17-one | |
| 0.0008 | - |
non-competitive inhibition, specific inhibitor, Ki: 0.000523 mM, IC50 about 0.0008 mM, 208fold higher affinity for the enzyme than substrate lanosterol | Rattus norvegicus | Triparanol | |
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