Reductive nitrosylation of ferric carboxymethylated-cytochrome c

2017 ◽  
Vol 21 (01) ◽  
pp. 1-9 ◽  
Author(s):  
Paolo Ascenzi ◽  
Chiara Ciaccio ◽  
Giovanna De Simone ◽  
Roberto Santucci ◽  
Massimo Coletta
Keyword(s):  
Cytochrome C ◽  
Axial Ligand ◽  
Ligand Concentration ◽  
Anaerobic Conditions ◽  
Reductive Nitrosylation ◽  
Axial Bond ◽  
Kinetics Of ◽  
Mediated Reduction

Horse heart carboxymethylated-cyt[Formula: see text] (CM-cyt[Formula: see text] displays myoglobin-like properties due to the cleavage of the heme-Fe-Met80 axial bond. Here, reductive nitrosylation of CM-cyt[Formula: see text](III) between pH 8.5 and 9.5, at [Formula: see text] 20.0 C, is reported. Under anaerobic conditions, the addition of NO to CM-cyt[Formula: see text](III) leads to the transient formation of CM-cyt[Formula: see text](III)-NO in equilibrium with CM-cyt[Formula: see text](II)-NO[Formula: see text]. In turn, CM-cyt[Formula: see text](II)-NO[Formula: see text] is converted to CM-cyt[Formula: see text](II) by OH[Formula: see text]-based catalysis. Then, CM-cyt[Formula: see text](II) binds NO very rapidly leading to CM-cyt[Formula: see text](II)-NO. Kinetics of NO binding to CM-cyt[Formula: see text](III) is independent of the ligand concentration, [Formula: see text] values ranging between 3.6 ± 0.4 s[Formula: see text] and 7.1 ± 0.7 s[Formula: see text]. This indicates that the formation of the CM-cytc(III)-NO complex is rate-limited by the cleavage of the weak heme-Fe(III) distal bond (likely Lys79). The conversion of CM-cyt[Formula: see text](III)-NO to CM-cyt[Formula: see text](II)-NO is rate-limited by the OH[Formula: see text]-mediated reduction of CM-cyt[Formula: see text](II)-NO[Formula: see text] ([Formula: see text] (1.2 ± 0.1) × 103 M[Formula: see text].s[Formula: see text]. Lastly, the very fast nitrosylation of CM-cyt[Formula: see text](II) takes place, values of [Formula: see text] ranging between[Formula: see text]5.3 × 106 M[Formula: see text].s[Formula: see text] and 1.4 × 107 M[Formula: see text].s[Formula: see text]. These results indicate that CM-cyt[Formula: see text] behaves as the cardiolipin-cyt[Formula: see text] complex highlighting the role of the sixth axial ligand of the heme-Fe atom in the modulation of the metal-based reactivity.

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.

New highly efficient coulometric cell with homogenous potential distribution on the working electrode

1986 ◽  
Vol 51 (3) ◽  
pp. 636-642
Author(s):  
Michal Németh ◽  
Ján Mocák
Keyword(s):  
Chemical Reactions ◽  
Potential Distribution ◽  
Anaerobic Conditions ◽  
Highly Efficient ◽  
Working Electrode ◽  
Constant Potential ◽  
Quantitative Analyses ◽  
Mechanism And Kinetics ◽  
Kinetics Of

A highly efficient coulometric cell was designed and constructed, ensuring a constant potential over the whole surface of the working electrode and suitable for very rapid electrolysis. It consists of concentric cylindrical Teflon parts; also the working and auxiliary electrodes are cylindrical and concentric. Electrolysis can be carried out under anaerobic conditions. Functioning of the cell was tested on the oxidation of hexacyanoferrate(II) and chlorpromazine and reduction of hexacyanoferrate(III). The new cell is suitable for routine quantitative analyses and in studying the mechanism and kinetics of moderately rapid chemical reactions.

Thermodynamic and Kinetic Investigation of the Solvent Effect on the Oxidation of [Co(en)2SCH2COO]+ with S2O82- In Water-Methanol and Water-tert-Butyl Alcohol Mixtures

1993 ◽  
Vol 58 (5) ◽  
pp. 1001-1006 ◽  
Author(s):  
Oľga Vollárová ◽  
Ján Benko
Keyword(s):  
Transfer Functions ◽  
Activation Parameters ◽  
Butyl Alcohol ◽  
Oxidation Of Co ◽  
Kinetics Of Oxidation ◽  
Tert Butyl ◽  
Tert Butyl Alcohol ◽  
Alcohol Mixtures ◽  
Kinetics Of

The kinetics of oxidation of [Co(en)2SCH2COO]+ with S2O82- was studied in water-methanol and water-tert-butyl alcohol mixtures. Changes in the reaction activation parameters ∆H≠ and ∆S≠ with varying concentration of the co-solvent depend on the kind of the latter, which points to a significant role of salvation effects. The solvation effect on the reaction is discussed based on a comparison of the transfer functions ∆Ht0, ∆St0 and ∆Gt0 for the initial and transition states with the changes in the activation parameters accompanying changes in the CO-solvent concentration. The transfer enthalpies of the reactant were obtained from calorimetric measurements.

scholarly journals Association between perinatal factors, genetic susceptibility to obesity and age at adiposity rebound in children of the EDEN mother–child cohort

2021 ◽  
Author(s):  
Aminata Hallimat Cissé ◽  
Sandrine Lioret ◽  
Blandine de Lauzon-Guillain ◽  
Anne Forhan ◽  
Ken K. Ong ◽  
...  
Keyword(s):  
Weight Gain ◽  
Genetic Susceptibility ◽  
Gestational Weight Gain ◽  
Gestational Age ◽  
Obesity Risk ◽  
Perinatal Factors ◽  
Gestational Weight ◽  
Adiposity Rebound ◽  
Kinetics Of

Abstract Background Early adiposity rebound (AR) has been associated with increased risk of overweight or obesity in adulthood. However, little is known about early predictors of age at AR. We aimed to study the role of perinatal factors and genetic susceptibility to obesity in the kinetics of AR. Methods Body mass index (BMI) curves were modelled by using mixed-effects cubic models, and age at AR was estimated for 1415 children of the EDEN mother–child cohort study. A combined obesity risk-allele score was calculated from genotypes for 27 variants identified by genome-wide association studies of adult BMI. Perinatal factors of interest were maternal age at delivery, parental education, parental BMI, gestational weight gain, maternal smoking during pregnancy, and newborn characteristics (sex, prematurity, and birth weight). We used a hierarchical level approach with multivariable linear regression model to investigate the association between these factors, obesity risk-allele score, and age at AR. Results A higher genetic susceptibility to obesity score was associated with an earlier age at AR. At the most distal level of the hierarchical model, maternal and paternal educational levels were positively associated with age at AR. Children born to parents with higher BMI were more likely to exhibit earlier age at AR. In addition, higher gestational weight gain was related to earlier age at AR. For children born small for gestational age, the average age at AR was 88 [±39] days lower than for children born appropriate for gestational age and 91 [±56] days lower than for children born large for gestational age. Conclusion The timing of AR seems to be an early childhood manifestation of the genetic susceptibility to adult obesity. We further identified low birth weight and gestational weight gain as novel predictors of early AR, highlighting the role of the intrauterine environment in the kinetics of adiposity.

scholarly journals Phosphorylation of GAPVD1 Is Regulated by the PER Complex and Linked to GAPVD1 Degradation

2021 ◽  
Vol 22 (7) ◽  
pp. 3787
Author(s):  
Hussam Ibrahim ◽  
Philipp Reus ◽  
Anna Katharina Mundorf ◽  
Anna-Lena Grothoff ◽  
Valerie Rudenko ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Transcriptional Repression ◽  
Small Gtpase ◽  
Main Role ◽  
Interacting Proteins ◽  
Casein Kinase 1 ◽  
Bona Fide ◽  
Kinetics Of

Repressor protein period (PER) complexes play a central role in the molecular oscillator mechanism of the mammalian circadian clock. While the main role of nuclear PER complexes is transcriptional repression, much less is known about the functions of cytoplasmic PER complexes. We found with a biochemical screen for PER2-interacting proteins that the small GTPase regulator GTPase-activating protein and VPS9 domain-containing protein 1 (GAPVD1), which has been identified previously as a component of cytoplasmic PER complexes in mice, is also a bona fide component of human PER complexes. We show that in situ GAPVD1 is closely associated with casein kinase 1 delta (CSNK1D), a kinase that regulates PER2 levels through a phosphoswitch mechanism, and that CSNK1D regulates the phosphorylation of GAPVD1. Moreover, phosphorylation determines the kinetics of GAPVD1 degradation and is controlled by PER2 and a C-terminal autoinhibitory domain in CSNK1D, indicating that the regulation of GAPVD1 phosphorylation is a novel function of cytoplasmic PER complexes and might be part of the oscillator mechanism or an output function of the circadian clock.

Sign in / Sign up

Export Citation Format

Share Document