scholarly journals Evidence That Compound I Is the Active Species in Both the Hydroxylase and Lyase Steps by Which P450scc Converts Cholesterol to Pregnenolone: EPR/ENDOR/Cryoreduction/Annealing Studies

Biochemistry ◽  
2015 ◽  
Vol 54 (48) ◽  
pp. 7089-7097 ◽  
Author(s):  
Roman Davydov ◽  
Natallia Strushkevich ◽  
David Smil ◽  
Aliaksei Yantsevich ◽  
Andrey Gilep ◽  
...  
Keyword(s):  
Active Species ◽  
Compound I

Computational Study on Compound I Redox-Active Species in Horseradish Peroxydase Enzyme: Conformational Fluctuations and Solvation Effects

2010 ◽  
Vol 114 (20) ◽  
pp. 6817-6824 ◽  
Author(s):  
Costantino Zazza ◽  
Amedeo Palma ◽  
Nico Sanna ◽  
Simone Tatoli ◽  
Massimiliano Aschi
Keyword(s):  
Computational Study ◽  
Active Species ◽  
Compound I ◽  
Solvation Effects ◽  
Redox Active

scholarly journals Mechanism of 17α,20-Lyase and New Hydroxylation Reactions of Human Cytochrome P450 17A1

2016 ◽  
Vol 291 (33) ◽  
pp. 17143-17164 ◽  
Author(s):  
Francis K. Yoshimoto ◽  
Eric Gonzalez ◽  
Richard J. Auchus ◽  
F. Peter Guengerich
Keyword(s):  
Acetic Acid ◽  
Cytochrome P450 ◽  
Bond Cleavage ◽  
Active Species ◽  
Sterol Biosynthesis ◽  
Compound I ◽  
Human Cytochrome ◽  
Acetyl Radical

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 (FeO3+, compound I) chemistry. We reinvestigated the 17α-hydroxyprogesterone and 17α-hydroxypregnenolone 17α,20-lyase reactions of human P450 17A1 and found incorporation of one 18O atom (from 18O2) 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 FeO3+ species) but not by H2O2. We propose three mechanisms that can involve the FeO3+ entity and that explain the 18O 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.

Principal Active Species of Horseradish Peroxidase, Compound I:  A Hybrid Quantum Mechanical/Molecular Mechanical Study

2005 ◽  
Vol 127 (39) ◽  
pp. 13611-13621 ◽  
Author(s):  
Etienne Derat ◽  
Shimrit Cohen ◽  
Sason Shaik ◽  
Ahmet Altun ◽  
Walter Thiel
Keyword(s):  
Horseradish Peroxidase ◽  
Active Species ◽  
Quantum Mechanical ◽  
Compound I ◽  
Mechanical Study

Activation of cytochrome c to a peroxidase compound I-type intermediate by H2O2: relevance to redox signalling in apoptosis

2004 ◽  
Vol 71 ◽  
pp. 97-106 ◽  
Author(s):  
Mark Burkitt ◽  
Clare Jones ◽  
Andrew Lawrence ◽  
Peter Wardman
Keyword(s):  
Cytochrome C ◽  
Hydroxyl Radical ◽  
Redox Regulation ◽  
Chemotherapeutic Agents ◽  
Tyrosyl Radical ◽  
Compound I ◽  
Definitive Evidence ◽  
Enhanced Production ◽  
Physico Chemical

The release of cytochrome c from mitochondria during apoptosis results in the enhanced production of superoxide radicals, which are converted to H2O2 by Mn-superoxide dismutase. We have been concerned with the role of cytochrome c/H2O2 in the induction of oxidative stress during apoptosis. Our initial studies showed that cytochrome c is a potent catalyst of 2′,7′-dichlorofluorescin oxidation, thereby explaining the increased rate of production of the fluorophore 2′,7′-dichlorofluorescein in apoptotic cells. Although it has been speculated that the oxidizing species may be a ferryl-haem intermediate, no definitive evidence for the formation of such a species has been reported. Alternatively, it is possible that the hydroxyl radical may be generated, as seen in the reaction of certain iron chelates with H2O2. By examining the effects of radical scavengers on 2′,7′-dichlorofluorescin oxidation by cytochrome c/H2O2, together with complementary EPR studies, we have demonstrated that the hydroxyl radical is not generated. Our findings point, instead, to the formation of a peroxidase compound I species, with one oxidizing equivalent present as an oxo-ferryl haem intermediate and the other as the tyrosyl radical identified by Barr and colleagues [Barr, Gunther, Deterding, Tomer and Mason (1996) J. Biol. Chem. 271, 15498-15503]. Studies with spin traps indicated that the oxo-ferryl haem is the active oxidant. These findings provide a physico-chemical basis for the redox changes that occur during apoptosis. Excessive changes (possibly catalysed by cytochrome c) may have implications for the redox regulation of cell death, including the sensitivity of tumour cells to chemotherapeutic agents.

Invasive species in the flora of Ukraine. I. The group of highly active species

Geo&Bio ◽  
2019 ◽  
Vol 2019 (17) ◽  
pp. 116-135 ◽  
Author(s):  
Vira V. Protopopova ◽  
◽  
Myroslav Shevera
Keyword(s):  
Invasive Species ◽  
Active Species ◽  
Highly Active

Structural Study of a new Compound Based on Acid 1,4-Cyclohexanedicarboxylic (1,4-CDC)

2010 ◽  
Vol 6 (1) ◽  
pp. 891-896
Author(s):  
Manel Halouani ◽  
M. Dammak ◽  
N. Audebrand ◽  
L. Ktari
Keyword(s):  
Aqueous Solution ◽  
Water Molecules ◽  
Carboxyl Group ◽  
X Ray Diffraction ◽  
Compound I ◽  
Unit Cell Parameters ◽  
Monoclinic System ◽  
X Ray ◽  
Cell Parameters ◽  
Cyclohexanedicarboxylic Acid

One nickel 1,4-cyclohexanedicarboxylate coordination polymers, Ni2 [(O10C6H4)(COO)2].2H2O  (I), was hydrothermally synthesized from an aqueous solution of Ni (NO3)2.6H2O, (1,4-CDC) (1,4-CDC = 1,4-cyclohexanedicarboxylic acid) and tetramethylammonium nitrate. Compound (I) crystallizes in the monoclinic system with the C2/m space group. The unit cell parameters are a = 20.1160 (16) Å, b = 9.9387 (10) Å, c = 6.3672 (6) Å, β = 97.007 (3) (°), V= 1263.5 (2) (Å3) and Dx= 1.751g/cm3. The refinement converged into R= 0.036 and RW = 0.092. The structure, determined by single crystal X-ray diffraction, consists of two nickel atoms Ni (1) and Ni (2). Lots of ways of which is surrounded by six oxygen atoms, a carboxyl group and two water molecules.

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