Enzymes
UniProtKB help_outline | 382 proteins |
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- Name help_outline albendazole Identifier CHEBI:16664 (Beilstein: 752696; CAS: 54965-21-8) help_outline Charge 0 Formula C12H15N3O2S InChIKeyhelp_outline HXHWSAZORRCQMX-UHFFFAOYSA-N SMILEShelp_outline CCCSc1ccc2[nH]c(NC(=O)OC)nc2c1 2D coordinates Mol file for the small molecule Search links Involved in 3 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H+ Identifier CHEBI:15378 Charge 1 Formula H InChIKeyhelp_outline GPRLSGONYQIRFK-UHFFFAOYSA-N SMILEShelp_outline [H+] 2D coordinates Mol file for the small molecule Search links Involved in 9,176 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline NADPH Identifier CHEBI:57783 (Beilstein: 10411862) help_outline Charge -4 Formula C21H26N7O17P3 InChIKeyhelp_outline ACFIXJIJDZMPPO-NNYOXOHSSA-J SMILEShelp_outline NC(=O)C1=CN(C=CC1)[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OC[C@H]2O[C@H]([C@H](OP([O-])([O-])=O)[C@@H]2O)n2cnc3c(N)ncnc23)[C@@H](O)[C@H]1O 2D coordinates Mol file for the small molecule Search links Involved in 1,247 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline O2 Identifier CHEBI:15379 (CAS: 7782-44-7) help_outline Charge 0 Formula O2 InChIKeyhelp_outline MYMOFIZGZYHOMD-UHFFFAOYSA-N SMILEShelp_outline O=O 2D coordinates Mol file for the small molecule Search links Involved in 2,648 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline albendazole S-oxide Identifier CHEBI:16959 (Beilstein: 677664; CAS: 54029-12-8) help_outline Charge 0 Formula C12H15N3O3S InChIKeyhelp_outline VXTGHWHFYNYFFV-UHFFFAOYSA-N SMILEShelp_outline CCCS(=O)c1ccc2[nH]c(NC(=O)OC)nc2c1 2D coordinates Mol file for the small molecule Search links Involved in 2 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H2O Identifier CHEBI:15377 (Beilstein: 3587155; CAS: 7732-18-5) help_outline Charge 0 Formula H2O InChIKeyhelp_outline XLYOFNOQVPJJNP-UHFFFAOYSA-N SMILEShelp_outline [H]O[H] 2D coordinates Mol file for the small molecule Search links Involved in 6,048 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline NADP+ Identifier CHEBI:58349 Charge -3 Formula C21H25N7O17P3 InChIKeyhelp_outline XJLXINKUBYWONI-NNYOXOHSSA-K SMILEShelp_outline NC(=O)c1ccc[n+](c1)[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OC[C@H]2O[C@H]([C@H](OP([O-])([O-])=O)[C@@H]2O)n2cnc3c(N)ncnc23)[C@@H](O)[C@H]1O 2D coordinates Mol file for the small molecule Search links Involved in 1,253 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
RHEA:10796 | RHEA:10797 | RHEA:10798 | RHEA:10799 | |
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Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
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Publications
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Chiral sulfoxidation of albendazole by the flavin adenine dinucleotide-containing and cytochrome P450-dependent monooxygenases from rat liver microsomes.
Moroni P., Buronfosse T., Longin-Sauvageon C., Delatour P., Benoit E.
The enantioselectivity of the in vitro sulfoxidation of the prochiral drug albendazole was investigated in rat liver microsomes. When biological material obtained from control rats and phenobarbital-, 3-methylcholanthrene-, or dexamethazone-pretreated rats was subjected to specific immunological a ... >> More
The enantioselectivity of the in vitro sulfoxidation of the prochiral drug albendazole was investigated in rat liver microsomes. When biological material obtained from control rats and phenobarbital-, 3-methylcholanthrene-, or dexamethazone-pretreated rats was subjected to specific immunological and chemical inhibitors, it was shown that two main enzymatic systems--cytochrome P450s and flavin-containing monooxygenase (FMO)--were responsible for the sulfoxidation. Purified FMO from rat liver was used to study the enantioselectivity of this enzyme in the sulfoxidation of albendazole. The enantiospecificity of FMO is the reverse of that of the P450s. Nevertheless, each P450 isoenzyme involved in this reaction presents its own individual stereoselectivity. << Less
Drug Metab. Dispos. 23:160-165(1995) [PubMed] [EuropePMC]
This publication is cited by 2 other entries.
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Relative contribution of cytochromes P-450 and flavin-containing monooxygenases to the metabolism of albendazole by human liver microsomes.
Rawden H.C., Kokwaro G.O., Ward S.A., Edwards G.
<h4>Aims</h4>Albendazole (ABZ; methyl 5-propylthio-1H-benzimidazol-2-yl carbamate) is a broad spectrum anthelmintic whose activity resides both in the parent compound and its sulphoxide metabolite (ABS). There are numerous reports of ABZ metabolism in animals but relatively few in humans. We have ... >> More
<h4>Aims</h4>Albendazole (ABZ; methyl 5-propylthio-1H-benzimidazol-2-yl carbamate) is a broad spectrum anthelmintic whose activity resides both in the parent compound and its sulphoxide metabolite (ABS). There are numerous reports of ABZ metabolism in animals but relatively few in humans. We have investigated the sulphoxidation of ABZ in human liver microsomes and recombinant systems.<h4>Methods</h4>The specific enzymes involved in the sulphoxidation of ABZ were determined by a combination of approaches; inhibition with an antiserum directed against cytochrome P450 reductase, the effect of selective chemical inhibitors on ABZ sulphoxidation in human liver microsomes, the capability of expressed CYP and FMO to mediate the formation of ABS, regression analysis of the rate of metabolism of ABZ to ABS in human liver microsomes against selective P450 substrates and regression analysis of the rate of ABS sulphoxidation against CYP expression measured by Western blotting.<h4>Results</h4>Comparison of Vmax values obtained following heat inactivation (3min at 45 degrees C) of flavin monoxygenases (FMO), chemical inhibition of FMO with methimazole and addition of an antiserum directed against cytochrome P450 reductase indicate that FMO and CYP contribute approximately 30% and 70%, respectively, to ABS production in vitro. Comparison of CLint values suggests CYP is a major contributor in vivo. A significant reduction in ABZ sulphoxidation (n = 3) was seen with ketoconazole (CYP3 A4; 32-37%), ritonavir (CYP3 A4: 34-42%), methimazole (FMO: 28-49%) and thioacetamide (FMO; 32-35%). Additive inhibition with ketoconazole and methimazole was 69 +/-8% (n = 3). ABS production in heat - treated microsomes (3 min at 45 degrees C) correlated significantly with testosterone 6beta-hydroxylation (CYP3A4; P < 0.05) and band intensities on Western blots probed with an antibody selective for 3A4 (P < 0.05). Recombinant human CYP3 A4, CYP1A2 and FMO3 produced ABS in greater quantities than control microsomes, with those expressing CYP3A4 producing threefold more ABS than those expressing CYP1A2. Kinetic studies showed the Km values obtained with both CYP3A4 and FMO3 were similar.<h4>Conclusions</h4>We conclude that the production of ABS in human liver is mediated via both FMO and CYP, principally CYP3A4, with the CYP component being the major contributor. << Less
Br. J. Clin. Pharmacol. 49:313-322(2000) [PubMed] [EuropePMC]
This publication is cited by 2 other entries.
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Sulfoxidation of albendazole by a cytochrome P450-independent monooxygenase from rat liver microsomes.
Fargetton X., Galtier P., Delatour P.
The in vitro biological oxidation of albendazole to albendazole sulfoxide by rat liver microsomes has been studied. This reaction corresponds to a NADPH-dependent enzymatic system, characterised by Km and Vm values of 53.6 microM and 0.59 nmole/mg protein per min. The rate of sulfoxidation by live ... >> More
The in vitro biological oxidation of albendazole to albendazole sulfoxide by rat liver microsomes has been studied. This reaction corresponds to a NADPH-dependent enzymatic system, characterised by Km and Vm values of 53.6 microM and 0.59 nmole/mg protein per min. The rate of sulfoxidation by liver microsomes of rats treated with phenobarbital, B-naphthoflavone, Aroclor 1254 and 3-methylcholanthrene was not increased. SKF 525A and metyrapone did not inhibit albendazole sulfoxidase. Thiobenzamide and tranylcypromine decreased sulfoxidation to 48 and 52% of control values. The inhibition by tranylcypromine was competitive. Purified flavin adenine dinucleotide (FAD)-containing monooxygenase from hog liver microsomes catalysed sulfoxidation of albendazole (V = 0.52 nmole/nmole enzyme per min). The present data demonstrate that sulfoxidation of albendazole in the rat liver is not catalysed by a cytochrome P450-dependent monooxygenase and suggest that albendazole is a substrate for FAD-containing monooxygenase (FMO). << Less