Enzymes
| UniProtKB help_outline | 223 proteins |
Reaction participants Show >> << Hide
- Name help_outline 3β-hydroxyandrost-5-en-17-one Identifier CHEBI:28689 (CAS: 53-43-0) help_outline Charge 0 Formula C19H28O2 InChIKeyhelp_outline FMGSKLZLMKYGDP-USOAJAOKSA-N SMILEShelp_outline [H][C@@]12CC=C3C[C@@H](O)CC[C@]3(C)[C@@]1([H])CC[C@]1(C)C(=O)CC[C@@]21[H] 2D coordinates Mol file for the small molecule Search links Involved in 9 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
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Namehelp_outline
reduced [NADPH—hemoprotein reductase]
Identifier
RHEA-COMP:11964
Reactive part
help_outline
- Name help_outline FMNH2 Identifier CHEBI:57618 (Beilstein: 6258176) help_outline Charge -2 Formula C17H21N4O9P InChIKeyhelp_outline YTNIXZGTHTVJBW-SCRDCRAPSA-L SMILEShelp_outline Cc1cc2Nc3c([nH]c(=O)[nH]c3=O)N(C[C@H](O)[C@H](O)[C@H](O)COP([O-])([O-])=O)c2cc1C 2D coordinates Mol file for the small molecule Search links Involved in 771 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline 3β,16α-dihydroxy-androst-5-en-17-one Identifier CHEBI:27771 (Beilstein: 2625823; CAS: 1232-73-1) help_outline Charge 0 Formula C19H28O3 InChIKeyhelp_outline QQIVKFZWLZJXJT-DNKQKWOHSA-N SMILEShelp_outline [H][C@@]12CC=C3C[C@@H](O)CC[C@]3(C)[C@@]1([H])CC[C@]1(C)C(=O)[C@H](O)C[C@@]21[H] 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 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 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
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Namehelp_outline
oxidized [NADPH—hemoprotein reductase]
Identifier
RHEA-COMP:11965
Reactive part
help_outline
- Name help_outline FMN Identifier CHEBI:58210 Charge -3 Formula C17H18N4O9P InChIKeyhelp_outline ANKZYBDXHMZBDK-SCRDCRAPSA-K SMILEShelp_outline C12=NC([N-]C(C1=NC=3C(N2C[C@@H]([C@@H]([C@@H](COP(=O)([O-])[O-])O)O)O)=CC(=C(C3)C)C)=O)=O 2D coordinates Mol file for the small molecule Search links Involved in 781 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
| RHEA:47220 | RHEA:47221 | RHEA:47222 | RHEA:47223 | |
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| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
| UniProtKB help_outline |
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Publications
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Differential catalytic properties in metabolism of endogenous and exogenous substrates among CYP3A enzymes expressed in COS-7 cells.
Ohmori S., Nakasa H., Asanome K., Kurose Y., Ishii I., Hosokawa M., Kitada M.
The catalytic properties of CYP3A7 in the metabolism of endogenous and exogenous substrates were compared with those of CYP3A4 and CYP3A5 using COS-7 expressing enzymes. The highest activities of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone 3-sulfate (DHEA-S) 16alpha-hydroxylase were o ... >> More
The catalytic properties of CYP3A7 in the metabolism of endogenous and exogenous substrates were compared with those of CYP3A4 and CYP3A5 using COS-7 expressing enzymes. The highest activities of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone 3-sulfate (DHEA-S) 16alpha-hydroxylase were observed in COS-7 cells expressing CYP3A7. In contrast, the activity of testosterone 6beta-hydroxylase of CYP3A7 expressed in COS-7 cells was much less than that of CYP3A4 expressed in COS-7 cells. The rate of carbamazepine 10, 11-epoxidation was the greatest in COS-7 cells expressing CYP3A4, followed by CYP3A5 and CYP3A7. On the other hand, the formation of reductive metabolite of zonisamide was the highest in COS-7 cells expressing CYP3A4, followed by CYP3A7 and CYP3A5. Furthermore, the addition of triazolam resulted in a decrease in 6beta-hydroxylation catalyzed by CYP3A7, but not by CYP3A4, whereas the pretreatment of microsomes with triacetyloleandomycin (TAO) resulted in a decrease in the reaction catalyzed by CYP3A4, but not by CYP3A7. Together with these results, it was suggested that CYP3A7 exerts differential catalytic properties not only in metabolism of endogenous substrates but also in drug metabolism compared to CYP3A4 and CYP3A5. << Less
Biochim. Biophys. Acta 1380:297-304(1998) [PubMed] [EuropePMC]
This publication is cited by 2 other entries.
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Helices F-G are important for the substrate specificities of CYP3A7.
Torimoto N., Ishii I., Toyama K., Hata M., Tanaka K., Shimomura H., Nakamura H., Ariyoshi N., Ohmori S., Kitada M.
CYP3A7 is a member of the human CYP3A family and a major form of P450 expressed in human fetal livers. Although CYP3A7 shares nearly 90% base sequence with CYP3A4, CYP3A7 shows striking functional differences in the catalytic preference for several substrates, such as dehydroepiandrosterone (DHEA) ... >> More
CYP3A7 is a member of the human CYP3A family and a major form of P450 expressed in human fetal livers. Although CYP3A7 shares nearly 90% base sequence with CYP3A4, CYP3A7 shows striking functional differences in the catalytic preference for several substrates, such as dehydroepiandrosterone (DHEA) or dehydroepiandrosterone 3-sulfate (DHEA-3S). First, to clarify the reason for the differences between CYP3A7 and CYP3A4, a homology model of CYP3A7 was constructed using the CYP3A4 crystal structure. Because these two structures were similar, four kinds of chimeric enzymes were constructed to determine which sequences are important for exhibiting the characteristics of CYP3A7. The results of kinetic analysis of DHEA and DHEA-3S 16alpha-hydroxylations by CYP3A7, CYP3A4, and CYP3A chimeras suggested that the amino acid residues from Leu(210) to Glu(279) were important to express the specificity for substrates as CYP3A7. This region was on the F and G helices of the modeled CYP3A7. Furthermore, to assess which amino acid in this sequence is important for the substrate specificity of CYP3A7, a one-point mutation of CYP3A7 to CYP3A4 was made by site-directed mutagenesis. The mutants of K224T and K244E had lost DHEA and DHEA-3S 16alpha-hydroxylation activities. The mutants also greatly decreased the metabolism of testosterone, erythromycin, nevirapine, and triazolam relative to those activities of CYP3A7 wild-type enzyme. From these results, it is expected that CYP3A7 can recognize specific substrates using the lysines in F-G loops. << Less
Drug Metab. Dispos. 35:484-492(2007) [PubMed] [EuropePMC]
This publication is cited by 2 other entries.
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Mechanism of 17alpha,20-Lyase and New Hydroxylation Reactions of Human Cytochrome P450 17A1: 18O LABELING AND OXYGEN SURROGATE EVIDENCE FOR A ROLE OF A PERFERRYL OXYGEN.
Yoshimoto F.K., Gonzalez E., Auchus R.J., Guengerich F.P.
Cytochrome P450 (P450) reactions can involve C-C bond cleavage, and several of these are critical in steroid and sterol biosynthesis. The mechanisms of P450s 11A1, 17A1, 19A1, and 51A1 have been controversial, in the context of the role of ferric peroxide (FeO2 (-)) versus perferryl (FeO(3+), comp ... >> More
Cytochrome P450 (P450) reactions can involve C-C bond cleavage, and several of these are critical in steroid and sterol biosynthesis. The mechanisms of P450s 11A1, 17A1, 19A1, and 51A1 have been controversial, in the context of the role of ferric peroxide (FeO2 (-)) versus perferryl (FeO(3+), compound I) chemistry. We reinvestigated the 17α-hydroxyprogesterone and 17α-hydroxypregnenolone 17α,20-lyase reactions of human P450 17A1 and found incorporation of one (18)O atom (from (18)O2) into acetic acid, consonant with proposals for a ferric peroxide mechanism (Akhtar, M., Lee-Robichaud, P., Akhtar, M. E., and Wright, J. N. (1997) J. Steroid Biochem. Mol. Biol. 61, 127-132; Akhtar, M., Wright, J. N., and Lee-Robichaud, P. (2011) J. Steroid Biochem. Mol. Biol. 125, 2-12). However, the reactions were supported by iodosylbenzene (a precursor of the FeO(3+) species) but not by H2O2 We propose three mechanisms that can involve the FeO(3+) entity and that explain the (18)O label in the acetic acid, two involving the intermediacy of an acetyl radical and one a steroid 17,20-dioxetane. P450 17A1 was found to perform 16-hydroxylation reactions on its 17α-hydroxylated products to yield 16,17α-dihydroxypregnenolone and progesterone, suggesting the presence of an active perferryloxo active species of P450 17A1 when its lyase substrate is bound. The 6β-hydroxylation of 16α,17α-dihydroxyprogesterone and the oxidation of both 16α,17α-dihydroxyprogesterone and 16α,17α-dihydroxypregnenolone to 16-hydroxy lyase products were also observed. We provide evidence for the contribution of a compound I mechanism, although contribution of a ferric peroxide pathway in the 17α,20-lyase reaction cannot be excluded. << Less
J. Biol. Chem. 291:17143-17164(2016) [PubMed] [EuropePMC]
This publication is cited by 6 other entries.