ArticleJournal of the American Chemical Society2016
Isotope-Labeling Studies Support the Electrophilic Compound I Iron Active Species, FeO(3+), for the Carbon-Carbon Bond Cleavage Reaction of the Cholesterol Side-Chain Cleavage Enzyme, Cytochrome P450 11A1.
Article in Journal of the American Chemical Society, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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25 citing papers in PubMed, 43 citations in OpenAlex.
- Integrated proteomic profiling of serum, follicular fluid and ovarian tissue in dairy cows with inactive ovaries.BMC veterinary research · 2026Article
- Unveiling cytochrome P450 enzymes that catalyze steroid side-chain cleavage in bacteria.Nature communications · 2025Article
- Optimization of CYP27A1 recombinant protein expression.Protein expression and purification · 2025Article
- Cytochrome P450The Journal of biological chemistry · 2025Article
- Ultrasound-Assisted Microcontinuous Process Facilitates the Selective Deuteration of Steroid Hormones.Journal of labelled compounds & radiopharmaceuticals · 2025Article
- Electron transfer engineering of artificially designed cell factory for complete biosynthesis of steroids.Nature communications · 2025Article
- Mechanistic Perspective on C-N and C-S Bond Construction Catalyzed by Cytochrome P450 Enzymes.ACS bio & med chem Au · 2025Review
- Oral exposure to benzalkonium chlorides in male and female mice reveals alteration of the gut microbiome and bile acid profile.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Updates on Mechanisms of Cytochrome P450 Catalysis of Complex Steroid Oxidations.International journal of molecular sciences · 2024Review
- Calix[2]azolium[2]benzimidazolone hosts for selective binding of neutral substrates in water.Nature communications · 2024Article
- Oxygen-18 Labeling Defines a Ferric Peroxide (Compound 0) Mechanism in the Oxidative Deformylation of Aldehydes by Cytochrome P450 2B4.ACS catalysis · 2024Article
- HSD3B1 is an oxysterol 3β-hydroxysteroid dehydrogenase in human placenta.Open biology · 2023Article
- Engineering C-C Bond Cleavage Activity into a P450 Monooxygenase Enzyme.Journal of the American Chemical Society · 2023Article
- Investigating the Active Oxidants Involved in Cytochrome P450 Catalyzed Sulfoxidation Reactions.Chemistry (Weinheim an der Bergstrasse, Germany) · 2022Article
- Characterization of human adrenal cytochrome P450 11B2 products of progesterone and androstenedione oxidation.The Journal of steroid biochemistry and molecular biology · 2021Article
- Functional interactions of adrenodoxin with several human mitochondrial cytochrome P450 enzymes.Archives of biochemistry and biophysics · 2020Article
- A requirement for an active proton delivery network supports a compound I-mediated C-C bond cleavage in CYP51 catalysis.The Journal of biological chemistry · 2020Article
- Alternative modes of OJournal of inorganic biochemistry · 2020Article
- Human cytochrome P450 11B2 produces aldosterone by a processive mechanism due to the lactol form of the intermediate 18-hydroxycorticosterone.The Journal of biological chemistry · 2019Article
- SF-1 mediates reproductive toxicity induced by Cerium oxide nanoparticles in male mice.Journal of nanobiotechnology · 2019Article
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5 authors at 1 institution in 1 country.
Funding
Abstract
The enzyme cytochrome P450 11A1 cleaves the C20-C22 carbon-carbon bond of cholesterol to form pregnenolone, the first 21-carbon precursor of all steroid hormones. Various reaction mechanisms are possible for the carbon-carbon bond cleavage step of P450 11A1, and most current proposals involve the oxoferryl active species, Compound I (FeO(3+)). Compound I can either (i) abstract an O-H hydrogen atom or (ii) be attacked by a nucleophilic hydroxy group of its substrate, 20R,22R-dihydroxycholesterol. The mechanism of this carbon-carbon bond cleavage step was tested using (18)O-labeled molecular oxygen and purified P450 11A1. P450 11A1 was incubated with 20R,22R-dihydroxycholesterol in the presence of molecular oxygen ((18)O2), and coupled assays were used to trap the labile (18)O atoms in the enzymatic products (i.e., isocaproaldehyde and pregnenolone). The resulting products were derivatized and the (18)O content was analyzed by high-resolution mass spectrometry. P450 11A1 showed no incorporation of an (18)O atom into either of its carbon-carbon bond cleavage products, pregnenolone and isocaproaldehyde . The positive control experiments established retention of the carbonyl oxygens in the enzymatic products during the trapping and derivatization processes. These results reveal a mechanism involving an electrophilic Compound I species that reacts with nucleophilic hydroxy groups in the 20R,22R-dihydroxycholesterol intermediate of the P450 11A1 reaction to produce the key steroid pregnenolone.
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