ArticleBiochemistry2016
Cytochrome b5 Activates the 17,20-Lyase Activity of Human Cytochrome P450 17A1 by Increasing the Coupling of NADPH Consumption to Androgen Production.
Article in Biochemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 48 citations in OpenAlex.
- Mechanistic and spectroscopic characterization of human CYP17A1 in Nanodiscs.Journal of inorganic biochemistry · 2026Review
- Functional studies on the cytochrome P450 splice variants CYP4F3A and CYP4F3B unveil the basis for their distinct physiological functions.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- The curious family of cytochrome P450 4F fatty acid ω-hydroxylases: recent developments in their function and relevance for human health.Open biology · 2025Review
- Article
- Updates on Mechanisms of Cytochrome P450 Catalysis of Complex Steroid Oxidations.International journal of molecular sciences · 2024Review
- Steroidogenic cytochrome P450 enzymes as drug target.Toxicological research · 2024Review
- Tracking protein-protein interactions by NMR: conformational selection in human steroidogenic cytochrome P450 CYP17A1 induced by cytochromePhysical chemistry chemical physics : PCCP · 2024Article
- Selectivity of osilodrostat as an inhibitor of human steroidogenic cytochromes P450.The Journal of steroid biochemistry and molecular biology · 2023Article
- Solvent isotope effects in the catalytic cycle of P450 CYP17A1: Computational modeling of the hydroxylation and lyase reactions.Journal of inorganic biochemistry · 2023Article
- On 'Evidence for the participation of cytochrome b5 in hepatic microsomal mixed-function oxidation reactions' by Alfred Hildebrandt and Ronald W. Estabrook.Archives of biochemistry and biophysics · 2022Article
- Three pairs of surrogate redox partners comparison for Class I cytochrome P450 enzyme activity reconstitution.Communications biology · 2022Article
- Association of Insulin Resistance and Elevated Androgen Levels with Polycystic Ovarian Syndrome (PCOS): A Review of Literature.Journal of healthcare engineering · 2022Review
- CytochromeDrug metabolism and disposition: the biological fate of chemicals · 2021Article
- Steroidogenic cytochrome P450 17A1 structure and function.Molecular and cellular endocrinology · 2021Review
- Substrate-Specific Allosteric Effects on the Enhancement of CYP17A1 Lyase Efficiency by CytochromeJournal of the American Chemical Society · 2021Article
- Cytochrome P450 2E1 and its roles in disease.Chemico-biological interactions · 2020Review
- 11-Oxygenated androgens in health and disease.Nature reviews. Endocrinology · 2020Review
- Expression, purification, and functional reconstitution ofBiochimica et biophysica acta. Biomembranes · 2020Article
- Evidence of Allosteric Coupling between Substrate Binding and Adx Recognition in the Vitamin D Carbon-24 Hydroxylase CYP24A1.Biochemistry · 2020Article
- Specificity of the Redox Complex between Cytochrome P450 24A1 and Adrenodoxin Relies on Carbon-25 Hydroxylation of Vitamin-D Substrate.Drug metabolism and disposition: the biological fate of chemicals · 2019Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Human cytochrome P450 17A1 is required for all androgen biosynthesis and is the target of abiraterone, a drug used widely to treat advanced prostate cancer. P450 17A1 catalyzes both 17-hydroxylation and subsequent 17,20-lyase reactions with pregnenolone, progesterone, and allopregnanolone. The presence of cytochrome b5 (b5) markedly stimulates the 17,20-lyase reaction, with little effect on 17-hydroxylation; however, the mechanism of this b5 effect is not known. We determined the influence of b5 on coupling efficiency-defined as the ratio of product formation to NADPH consumption-in a reconstituted system using these 3 pairs of substrates for the 2 reactions. Rates of NADPH consumption ranged from 4 to 13 nmol/min/nmol P450 with wild-type P450 17A1. For the 17-hydroxylase reaction, progesterone oxidation was the most tightly coupled (∼50%) and negligibly changed upon addition of b5. Rates of NADPH consumption were similar for the 17-hydroxylase and corresponding 17,20-lyase reactions for each steroid series, and b5 only slightly increased NADPH consumption. For the 17,20-lyase reactions, b5 markedly increased product formation and coupling in parallel with all substrates, from 6% to 44% with the major substrate 17-hydroxypregnenolone. For the naturally occurring P450 17A1 mutations E305G and R347H, which impair 17,20-lyase activity, b5 failed to rescue the poor coupling with 17-hydroxypregnenolone (2-4%). When the conserved active-site threonine was mutated to alanine (T306A), both the activity and coupling were markedly decreased with all substrates. We conclude that b5 stimulation of the 17,20-lyase reaction primarily derives from more efficient use of NADPH for product formation rather than side products.
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