Rhea - reaction knowledgebase

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Name ^help_outline testosterone Identifier CHEBI:17347 (Beilstein: 3653705; CAS: 58-22-0) ^help_outline Charge 0 Formula C19H28O2 InChIKey^help_outline MUMGGOZAMZWBJJ-DYKIIFRCSA-N SMILES^help_outline [H][C@@]12CCC3=CC(=O)CC[C@]3(C)[C@@]1([H])CC[C@]1(C)[C@@H](O)CC[C@@]21[H] 2D coordinates Mol file for the small molecule Search links Involved in 19 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Name^help_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 InChIKey^help_outline YTNIXZGTHTVJBW-SCRDCRAPSA-L SMILES^help_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 852 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Search links Involved in 789 reaction(s) 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 2,851 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Name ^help_outline 15α,17β-dihydroxyandrost-4-en-3-one Identifier CHEBI:34161 (CAS: 2226-70-2) ^help_outline Charge 0 Formula C19H28O3 InChIKey^help_outline KYGUQDTWUBBBSD-MJVYMRHDSA-N SMILES^help_outline C[C@]12CC[C@H]3[C@@H](CCC4=CC(=O)CC[C@]34C)[C@@H]1[C@@H](O)C[C@@H]2O 2D coordinates Mol file for the small molecule Search links Involved in 1 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Name^help_outline oxidized [NADPH—hemoprotein reductase] Identifier RHEA-COMP:11965 Reactive part ^help_outline
- Name ^help_outline FMN Identifier CHEBI:58210 Charge -3 Formula C17H18N4O9P InChIKey^help_outline ANKZYBDXHMZBDK-SCRDCRAPSA-K SMILES^help_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 861 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Search links Involved in 789 reaction(s) Find proteins in UniProtKB for this molecule
Name ^help_outline H₂O Identifier CHEBI:15377 (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 6,485 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 9,932 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule

Cross-references

	RHEA:83131	RHEA:83132	RHEA:83133	RHEA:83134
Reaction direction	undefined	left-to-right	right-to-left	bidirectional
UniProtKB ^help_outline

Related reactions ^help_outline

More general form(s) of this reaction

RHEA:83179
a steroid + reduced [NADPH—hemoprotein reductase] + O₂ = a 15α-hydroxy steroid + oxidized [NADPH—hemoprotein reductase] + H₂O + H⁺

Publications

The structure and characterization of type I P-450(15) alpha gene as major steroid 15 alpha-hydroxylase and its comparison with type II P-450(15) alpha gene.

Lindberg R., Burkhart B., Ichikawa T., Negishi M.

The structures of genes 15 alpha OH-1 and 15 alpha OH-2, within the mouse steroid 15 alpha-hydroxylase (P-450(15) alpha) family were determined. Genes 15 alpha OH-1 and -2 encoded mouse Type I and II P-450(15) alpha, respectively (Squires, E.J., and Negishi, M. (1988) J. Biol. Chem. 263, 4166-4171 ... >> More

The structures of genes 15 alpha OH-1 and 15 alpha OH-2, within the mouse steroid 15 alpha-hydroxylase (P-450(15) alpha) family were determined. Genes 15 alpha OH-1 and -2 encoded mouse Type I and II P-450(15) alpha, respectively (Squires, E.J., and Negishi, M. (1988) J. Biol. Chem. 263, 4166-4171). The two genes, which spanned approximately 8 kilobase pairs of total length, showed nearly identical structures and were divided into nine exons at the same positions. A high nucleotide sequence homology (greater than 96%) indicated that 15 alpha OH-1 and -2 were duplicated within 5 million years. The two major transcription start sites were located at 14 and 24 base pairs (bp) upstream from the initiation Met in both genes. No tissue-specific difference in 15 alpha OH-1 and -2 transcriptional start sites was found in mouse liver and kidney. Both 15 alpha OH-1 and -2 had TATA and CAAT boxes at 30 and 100 bp, respectively, upstream from their major transcription start sites. A glucocorticoid regulatory element was present at 336 bp upstream from the start site in both genes. In addition to these motifs, 15 alpha OH-2 had an SV40 enhancer core sequence immediately downstream from its CAAT box. There were only 11 substitutions between Type I and II P-450(15) alpha in their 494-amino acid residues. Type I cDNA-transfected cell homogenates had testosterone 15 alpha-hydroxylase activity at approximately 9 pmol/min/mg protein. Type I also catalyzed progesterone and androstenedione 15 alpha-hydroxylase activities. Type II, on the other hand, exhibited little activity toward these steroids. The results indicated that Type I was the major steroid 15 alpha-hydroxylase. The differential 15 alpha OH-1 expression, therefore, determined the sexual dimorphism of the tissue-specific 15 alpha-hydroxylase activity in mice. << Less

J. Biol. Chem. 264:6465-6471(1989) [PubMed] [EuropePMC]

This publication is cited by 2 other entries.
Mouse liver testosterone 15 alpha-hydroxylase (cytochrome P-450(15) alpha). Purification, regioselectivity, stereospecificity, and sex-dependent expression.

Harada N., Negishi M.

Testosterone 15 alpha-hydroxylase (cytochrome P-450(15) alpha) was purified from female 129/J mouse liver microsomes based on its specific activities in the eluates from the columns of octylamino-Sepharose 4B, hydroxylapatite, DEAE-Bio-Gel A, and CM52 chromatography. The 15 alpha-hydroxylation act ... >> More

Testosterone 15 alpha-hydroxylase (cytochrome P-450(15) alpha) was purified from female 129/J mouse liver microsomes based on its specific activities in the eluates from the columns of octylamino-Sepharose 4B, hydroxylapatite, DEAE-Bio-Gel A, and CM52 chromatography. The 15 alpha-hydroxylation activity was five times higher in female than in male 129/J mouse liver microsomes. The specific cytochrome P-450 content of purified P-450(15) alpha fraction was 14.5 nmol/mg of protein. The Soret peak of the reduced cytochrome P-450-CO complex was 451 nm. The apparent subunit molecular weight of P-450(15) alpha was 48,000, and the protein appeared as only one major band on sodium dodecyl sulfate-polyacrylamide gels. The specific activity of testosterone 15 alpha-hydroxylation reconstituted with the purified P-450(15) alpha was 94 nmol/min/nmol of cytochrome P-450 and 1349 nmol/min/mg of protein, and these were about 65- and 1000-fold higher, respectively, than the activity of solubilized microsomes. The purified P-450(15) alpha exhibited high regioselectivity and stereospecificity for testosterone hydroxylation. More than 95% of the testosterone metabolites formed by the purified P-450(15) alpha was 15 alpha-hydroxytestosterone. Virtually 100% of mouse liver microsomal testosterone 15 alpha-hydroxylation activity can be accounted for by the purified P-450(15) alpha. The P-450(15) alpha fraction was able to catalyze benzphetamine N-demethylation, 7-ethoxycoumarin O-de-ethylation, aniline 4-hydroxylation, benzo(alpha)pyrene 3-hydroxylation, acetanilide 4-hydroxylation, and lauric acid (11 + 12)-hydroxylation at various turnover rates, indicating broad substrate specificity of the P-450(15) alpha for the oxidations of xenobiotics. This is in sharp contrast to high regioselectivity and stereospecificity for testosterone hydroxylation. << Less

J Biol Chem 259:1265-1271(1984) [PubMed] [EuropePMC]

RHEA:83131 testosterone + reduced [NADPH--hemoprotein reductase] + O2 = 15alpha,17beta-dihydroxyandrost-4-en-3-one + oxidized [NADPH--hemoprotein reductase] + H2O + H(+)

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Cross-references

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More general form(s) of this reaction

Publications

The structure and characterization of type I P-450(15) alpha gene as major steroid 15 alpha-hydroxylase and its comparison with type II P-450(15) alpha gene.

Mouse liver testosterone 15 alpha-hydroxylase (cytochrome P-450(15) alpha). Purification, regioselectivity, stereospecificity, and sex-dependent expression.

Related reactions ^help_outline