Rhea - reaction knowledgebase

Enzymes

UniProtKB ^help_outline	4 proteins
GO Molecular Function ^help_outline	GO:0047103 3-alpha,7-alpha,12-alpha-trihydroxycholestan-26-al 26-oxidoreductase activity

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Name ^help_outline (25R)-3α,7α,12α-trihydroxy-5β-cholestan-26-al Identifier CHEBI:48940 (Beilstein: 5620906) ^help_outline Charge 0 Formula C27H46O4 InChIKey^help_outline USFJGINJGUIFSY-IUFSEJPUSA-N SMILES^help_outline [H]C(=O)[C@H](C)CCC[C@@H](C)[C@@]1([H])CC[C@@]2([H])[C@]3([H])[C@H](O)C[C@]4([H])C[C@H](O)CC[C@]4(C)[C@@]3([H])C[C@H](O)[C@]12C 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 InChIKey^help_outline GPRLSGONYQIRFK-UHFFFAOYSA-N SMILES^help_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 O₂ Identifier CHEBI:15379 (CAS: 7782-44-7) ^help_outline Charge 0 Formula O2 InChIKey^help_outline MYMOFIZGZYHOMD-UHFFFAOYSA-N SMILES^help_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 reduced [adrenodoxin] Identifier RHEA-COMP:9998 Reactive part ^help_outline
- Name ^help_outline [2Fe-2S]¹⁺ Identifier CHEBI:33738 Charge 1 Formula Fe2S2 InChIKey^help_outline MAGIRAZQQVQNKP-UHFFFAOYSA-N SMILES^help_outline S1[Fe]S[Fe+]1 2D coordinates Mol file for the small molecule Search links Involved in 236 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Search links Involved in 54 reaction(s) Find proteins in UniProtKB for this molecule
Name ^help_outline (25R)-3α,7α,12α-trihydroxy-5β-cholestan-26-oate Identifier CHEBI:58734 Charge -1 Formula C27H45O5 InChIKey^help_outline CNWPIIOQKZNXBB-WBYPBBSPSA-M SMILES^help_outline [H][C@@]12C[C@H](O)CC[C@]1(C)[C@@]1([H])C[C@H](O)[C@]3(C)[C@]([H])(CC[C@@]3([H])[C@]1([H])[C@H](O)C2)[C@H](C)CCC[C@@H](C)C([O-])=O 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 H₂O Identifier CHEBI:15377 (Beilstein: 3587155; CAS: 7732-18-5) ^help_outline Charge 0 Formula H2O InChIKey^help_outline XLYOFNOQVPJJNP-UHFFFAOYSA-N SMILES^help_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 oxidized [adrenodoxin] Identifier RHEA-COMP:9999 Reactive part ^help_outline
- Name ^help_outline [2Fe-2S]²⁺ Identifier CHEBI:33737 Charge 2 Formula Fe2S2 InChIKey^help_outline XSOVBBGAMBLACL-UHFFFAOYSA-N SMILES^help_outline S1[Fe+]S[Fe+]1 2D coordinates Mol file for the small molecule Search links Involved in 236 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Search links Involved in 54 reaction(s) Find proteins in UniProtKB for this molecule

Cross-references

	RHEA:34627	RHEA:34628	RHEA:34629	RHEA:34630
Reaction direction	undefined	left-to-right	right-to-left	bidirectional
UniProtKB ^help_outline	4 proteins	4 proteins
Gene Ontology ^help_outline	GO:0047103
KEGG ^help_outline				R08761
MetaCyc ^help_outline		1.2.1.40-RXN

Publications

Putative helix F contributes to regioselectivity of hydroxylation in mitochondrial cytochrome P450 27A1.

Pikuleva I.A., Puchkaev A., Bjoerkhem I.

On the basis of alignment with structurally characterized cytochromes P450 (P450s), we have identified the putative F and G helices of mitochondrial P450s 27A1 and 11A. We introduced substitutions at Phe-207, Ile-211, and Phe-215 within putative helix F and at Trp-235 and Tyr-238 within putative h ... >> More

On the basis of alignment with structurally characterized cytochromes P450 (P450s), we have identified the putative F and G helices of mitochondrial P450s 27A1 and 11A. We introduced substitutions at Phe-207, Ile-211, and Phe-215 within putative helix F and at Trp-235 and Tyr-238 within putative helix G in P450 27A1 and compared wild type and mutants with respect to catalytic activity, product pattern, substrate binding, formation of hydrogen peroxide, and interaction with redox partner. Results indicate that the mutated residues are important for delivery of the correctly oriented substrate to the P450 active site. The I211K and F215K mutations, for example, affected the regioselectivity of P450 27A1-dependent hydroxylation reactions and conferred the P450 capacity to cleave the C-C bond of the substrate during the catalytic cycle. Studies of P450 11A1 indicate that Phe-202 has functions similar to those of its counterpart in P450 27A1 (Phe-215). We propose that putative helices F and G form the sides of the substrate-access channel, thus providing the additional mechanism to control regioselectivity of hydroxylation in mitochondrial P450s. << Less

Biochemistry 40:7621-7629(2001) [PubMed] [EuropePMC]

This publication is cited by 3 other entries.
Characterization of human sterol 27-hydroxylase. A mitochondrial cytochrome P-450 that catalyzes multiple oxidation reaction in bile acid biosynthesis.

Cali J.J., Russell D.W.

The enzyme sterol 27-hydroxylase catalyzes the first step in the oxidation of the side chain of sterol intermediates in the bile acid synthesis pathway. Human sterol 27-hydroxylase cDNAs were isolated from a liver cDNA library by cross-hybridization with a previously cloned rabbit cDNA probe. DNA ... >> More

The enzyme sterol 27-hydroxylase catalyzes the first step in the oxidation of the side chain of sterol intermediates in the bile acid synthesis pathway. Human sterol 27-hydroxylase cDNAs were isolated from a liver cDNA library by cross-hybridization with a previously cloned rabbit cDNA probe. DNA sequence analysis of hybridization-positive clones predicted a human sterol 27-hydroxylase consisting of a 33-amino-acid mitochondrial signal sequence followed by a mature protein of 498 amino acids. RNA blotting experiments demonstrated sterol 27-hydroxylase mRNAs of approximately 1.8 to 2.2 kilobases in liver and fibroblast cells. The steady state levels of the mRNA did not change when cultured cells were grown in the presence or absence of sterols. Introduction of the sterol 27-hydroxylase cDNA into Simian COS cells resulted in the expression of active enzyme capable of catalyzing multiple oxidation reactions (R-CH3----R-CH2OH----R-COOH) at carbon 27 of sterol intermediates of the bile acid synthesis pathway. << Less

J. Biol. Chem. 266:7774-7778(1991) [PubMed] [EuropePMC]

This publication is cited by 3 other entries.
Sterol 27-hydroxylase in bile acid biosynthesis. Mechanism of oxidation of 5 beta-cholestane-3 alpha,7 alpha,12 alpha,27-tetrol into 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid.

Holmberg-Betsholtz I., Lund E., Bjorkhem I., Wikvall K.

The sequence of reactions catalyzed by sterol 27-hydroxylase (CYP27) in the oxidation of 5 beta-cholestane-3 alpha,7 alpha,12 alpha,27-tetrol into 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid was studied with apparently homogeneous preparations of the cytochrome P-450 from rabbit l ... >> More

The sequence of reactions catalyzed by sterol 27-hydroxylase (CYP27) in the oxidation of 5 beta-cholestane-3 alpha,7 alpha,12 alpha,27-tetrol into 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid was studied with apparently homogeneous preparations of the cytochrome P-450 from rabbit liver mitochondria. Conditions are described for the formation and characterization of 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestane-27-al as an enzymatically generated intermediate in the oxidation process. Incubation of 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol or 5 beta-cholestane-3 alpha,7 alpha,12 alpha,27-tetrol with sterol 27-hydroxylase in 18O2 atmosphere resulted in the incorporation of one or two 18O atoms in the carboxyl group of 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid. Similar incubations with 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestane-27-al resulted in the incorporation of one 18O atom in the 27-carboxyl group. The results strongly indicate that the sterol 27-hydroxylase performs multiple monooxygenations in the conversion of 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol into 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid. The following reaction sequence (Reaction 1) at carbon 27 is proposed. [formula: see text] Reaction 1. << Less

J Biol Chem 268:11079-11085(1993) [PubMed] [EuropePMC]

This publication is cited by 3 other entries.

Comments

RHEA:34627 part of RHEA:34631

RHEA:34627 (25R)-3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-al + H(+) + O2 + 2 reduced [adrenodoxin] = (25R)-3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-oate + H2O + 2 oxidized [adrenodoxin]

Enzymes

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Cross-references

Publications

Putative helix F contributes to regioselectivity of hydroxylation in mitochondrial cytochrome P450 27A1.

Characterization of human sterol 27-hydroxylase. A mitochondrial cytochrome P-450 that catalyzes multiple oxidation reaction in bile acid biosynthesis.

Sterol 27-hydroxylase in bile acid biosynthesis. Mechanism of oxidation of 5 beta-cholestane-3 alpha,7 alpha,12 alpha,27-tetrol into 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid.

Comments