Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary for 1.3.1.72 extracted from

  • Bae, S.H.; Paik, Y.K.
    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.
    View publication on PubMedView publication on EuropePMC

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 [┬Ámol/min/mg] Specific Activity Maximum [┬Ámol/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