Complexation of intracellular cyanide by hydroxocobalamin using a human cellular model

1996 ◽  
Vol 15 (1) ◽  
pp. 19-25 ◽  
Author(s):  
Alain Astier ◽  
Frederic J Baud
Keyword(s):  
Human Fibroblasts ◽  
Cellular Model ◽  
Cyanide Poisoning ◽  
Order Process ◽  
Accumulation Ratio ◽  
First Order ◽  
High Affinity ◽  
Cobalt Compounds ◽  
Few Data ◽  
Complex Cyanide

1 The rational for administering hydroxocobalamin (OHCbl) as an antidote to cyanide poisoning is based on the high affinity ofCN ion for cobalt compounds. However, only few data are available on the influence of OHCbl on the intracellular cyanide pool. 2 In human fibroblasts incubated for 10 min with 500 μM of [14C] cyanide, the accumulation ratio was 25 at 37°C (10.45 ± 1.51 mM) and 11.9 at 4°C. 3 Using the monoblastic U-937 cell line, a rapid uptake of radioactive cyanide was observed with a maximum accumulation ratio of 1.97 at 5 min. 4 A linear relationship between cyanide uptake by U-937 cells and cyanide concentration in incubation medium (10-500 μM; 5 min) was found suggesting a first order process (k= 0.25 min-1). 5 After incubation of fibroblasts with 500 μM of OHCbl, a 75% decrease of intracellular cyanide was observed, with concomittant formation of intracellular cyanocobalamin CNCbl (intracellular/extracellular ratio: 158). 6 These findings suggest that OHCbl is able to penetrate into heavily cyanide loaded cells and to complex cyanide to the non-toxic CNCbl form.

scholarly journals REGENERATION OF VISUAL PURPLE IN SOLUTION

1939 ◽  
Vol 23 (1) ◽  
pp. 21-39 ◽  
Author(s):  
Aurin M. Chase ◽  
Emil L. Smith
Keyword(s):  
Order Process ◽  
First Order ◽  
Color Changes ◽  
Violet Light ◽  
Frog Retina ◽  
Significant Difference ◽  
Kinetics Of ◽  
Photosensitive Substance ◽  
Subsequent Regeneration

1. Measurements of visual purple regeneration in solution have been made by a procedure which minimized distortion of the results by other color changes so that density changes caused by the regenerating substance alone are obtained. 2. Bleaching a visual purple solution with blue and violet light causes a greater subsequent regeneration than does an equivalent bleaching with light which lacks blue and violet. This is due to a photosensitive substance which has a gradually increasing effective absorption toward the shorter wavelengths. It is uncertain whether this substance is a product of visual purple bleaching or is present in the solution before illumination. 3. The regeneration of visual purple measured at 560 mµ is maximal at about pH 6.7 and decreases markedly at more acid and more alkaline pH's. 4. The absorption spectrum of the regenerating material shows only a concentration change during the course of regeneration, but has a higher absorption at the shorter wavelengths than has visual purple before illumination. 5. Visual purple extractions made at various temperatures show no significant difference in per cent of regeneration. 6. The kinetics of regeneration is usually that of a first order process. Successive regenerations in the same solution have the same velocity constant but form smaller total amounts of regenerated substance. 7. In vivo, the frog retina shows no additional oxygen consumption while visual purple is regenerating.

Spectrochemical Behavior of Carcinogenic Polycyclic Aromatic Hydrocarbons in Biological Systems. Part II: A Theoretical Rate Model for BaP Metabolism in Living Cells

1996 ◽  
Vol 50 (11) ◽  
pp. 1352-1359 ◽  
Author(s):  
Ping Chiang ◽  
Kuang-Pang Li ◽  
Tong-Ming Hseu
Keyword(s):  
Rate Constant ◽  
Living Cells ◽  
Rate Model ◽  
Number Density ◽  
Order Process ◽  
Irreversible Reaction ◽  
First Order ◽  
Metabolism Rate ◽  
Polycyclic Aromatic ◽  
Kinetics Of

An idealized model for the kinetics of benzo[ a]pyrene (BaP) metabolism is established. As observed from experimental results, the BaP transfer from microcrystals to the cell membrane is definitely a first-order process. The rate constant of this process is signified as k1. We describe the surface–midplane exchange as reversible and use rate constants k2 and k3 to describe the inward and outward diffusions, respectively. The metabolism is identified as an irreversible reaction with a rate constant k4. If k2 and k3 are assumed to be fast and not rate determining, the effect of the metabolism rate, k4, on the number density of BaP in the midplane of the microsomal membrane, m3, can be estimated. If the metabolism rate is faster than or comparable to the distribution rates, k2 and k3, the BaP concentration in the membrane midplane, m3, will quickly be dissipated. But if k4 is extremely small, m3 will reach a plateau. Under conditions when k2 and k3 also play significant roles in determining the overall rate, more complicated patterns of m3 are expected.

scholarly journals Mechanistic and active-site studies on d(–)-mandelate dehydrogenase from Rhodotorula graminis

1992 ◽  
Vol 281 (1) ◽  
pp. 211-218 ◽  
Author(s):  
D P Baker ◽  
C Kleanthous ◽  
J N Keen ◽  
E Weinhold ◽  
C A Fewson
Keyword(s):  
Active Site ◽  
Complete Sequence ◽  
Histidine Residue ◽  
Extended Version ◽  
Order Process ◽  
First Order ◽  
Tryptic Digest ◽  
Complete Inactivation ◽  
Hydrolysis Of ◽  
High Voltage Electrophoresis

D(–)-Mandelate dehydrogenase, the first enzyme of the mandelate pathway in the yeast Rhodotorula graminis, catalyses the NAD(+)-dependent oxidation of D(–)-mandelate to phenylglyoxylate. D(–)-2-(Bromoethanoyloxy)-2-phenylethanoic acid [‘D(–)-bromoacetylmandelic acid’], an analogue of the natural substrate, was synthesized as a probe for reactive and accessible nucleophilic groups within the active site of the enzyme. D(–)-Mandelate dehydrogenase was inactivated by D(–)-bromoacetylmandelate in a psuedo-first-order process. D(–)-Mandelate protected against inactivation, suggesting that the residue that reacts with the inhibitor is located at or near the active site. Complete inactivation of the enzyme resulted in the incorporation of approx. 1 mol of label/mol of enzyme subunit. D(–)-Mandelate dehydrogenase that had been inactivated with 14C-labelled D(–)-bromoacetylmandelate was digested with trypsin; there was substantial incorporation of 14C into two tryptic-digest peptides, and this was lowered in the presence of substrate. One of the tryptic peptides had the sequence Val-Xaa-Leu-Glu-Ile-Gly-Lys, with the residue at the second position being the site of radiolabel incorporation. The complete sequence of the second peptide was not determined, but it was probably an N-terminally extended version of the first peptide. High-voltage electrophoresis of the products of hydrolysis of modified protein showed that the major peak of radioactivity co-migrated with N tau-carboxymethylhistidine, indicating that a histidine residue at the active site of the enzyme is the most likely nucleophile with which D(–)-bromoacetylmandelate reacts. D(–)-Mandelate dehydrogenase was incubated with phenylglyoxylate and either (4S)-[4-3H]NADH or (4R)-[4-3H]NADH and then the resulting D(–)-mandelate and NAD+ were isolated. The enzyme transferred the pro-R-hydrogen atom from NADH during the reduction of phenylglyoxylate. The results are discussed with particular reference to the possibility that this enzyme evolved by the recruitment of a 2-hydroxy acid dehydrogenase from another metabolic pathway.

scholarly journals GAMMA GLOBULIN TURNOVER IN RABBITS BEFORE AND DURING HYPERIMMUNIZATION

1964 ◽  
Vol 119 (4) ◽  
pp. 537-546 ◽  
Author(s):  
Stig Bryde Andersen ◽  
Mogens Bjørneboe
Keyword(s):  
Turnover Rate ◽  
Gamma Globulin ◽  
Order Process ◽  
First Order ◽  
Plasma Pool ◽  
Fractional Turnover

The turnover of 131I-labeled gamma globulin has been determined in rabbits before and during (8 weeks later) hyperimmunization with pneumococcic vaccine, which increased the gamma globulin concentration 5 to 10 times. Before immunization fractional turnover rate was an average of 36 per cent of the plasma pool per day, and the rate of catabolism was 133 mg/kg/day. During hyperimmunization fractional turnover rate was an average of 37 per cent per day, and the rate of catabolism was 1160 mg/kg/day. The observation that the fractional turnover rate is independent of the concentration suggests that the rate of breakdown should have the characteristic of a first order process.

Deep breath reversal and exponential return of methacholine-induced obstruction in asthmatic and nonasthmatic subjects

2004 ◽  
Vol 96 (1) ◽  
pp. 137-142 ◽  
Author(s):  
Andrew C. Jackson ◽  
Margaret M. Murphy ◽  
John Rassulo ◽  
Bartolome R. Celli ◽  
Roland H. Ingram
Keyword(s):  
Healthy Subjects ◽  
Time Course ◽  
Rapid Decrease ◽  
Airway Wall ◽  
Methacholine Challenge ◽  
Order Process ◽  
Deep Breath ◽  
First Order ◽  
Before And After ◽  
Complete Reversal

A deep breath (DB) during induced obstruction results in a transient reversal with a return to pre-DB levels in both asthmatic and nonasthmatic subjects. The time course of this transient recovery has been reported to be exponential by one group but linear by another group. In the present study, we estimated airway resistance (Raw) from measurements of respiratory system transfer impedance before and after a DB. Nine healthy subjects and nine asthmatic subjects were studied at their maximum response during a methacholine challenge. In all subjects, the DB resulted in a rapid decrease in Raw, which then returned to pre-DB levels. This recovery was well fit with a monoexponential function in both groups, and the time constant was significantly smaller in the asthmatic than the nonasthmatic subjects (11.6 ± 5.0 and 35.1 ± 15.9 s, respectively). Obstruction was completely reversed in the nonasthmatic subjects (pre- and postchallenge mean Raw immediately after the DB were 2.03 ± 0.66 and 2.06 ± 0.68 cmH2O·l-1·s, respectively), whereas in the asthmatic subjects complete reversal did not occur (2.29 ± 0.78 and 4.84 ± 2.64 cmH2O·l-1·s, respectively). Raw after the DB returned to postchallenge, pre-DB values in the nonasthmatic subjects (3.78 ± 1.56 and 3.97 ± 1.63 cmH2O·l-1·s, respectively), whereas in the asthmatic subjects it was higher but not significantly so (9.19 ± 4.95 and 7.14 ± 3.56 cmH2O·l-1·s, respectively). The monoexponential recovery suggests a first-order process such as airway wall-parenchymal tissue interdependence or renewed constriction of airway smooth muscle.

scholarly journals In vitro comparison of hydroxocobalamin (B12a) and the mitochondrial directed therapy by a succinate prodrug in a cellular model of cyanide poisoning

2020 ◽  
Vol 7 ◽  
pp. 1263-1271 ◽  
Author(s):  
Shawn Owiredu ◽  
Abhay Ranganathan ◽  
John C. Greenwood ◽  
Sarah Piel ◽  
Joanna I. Janowska ◽  
...  
Keyword(s):  
Cellular Model ◽  
Cyanide Poisoning ◽  
In Vitro Comparison

The lifetime of hydrogen adsorbed on a slightly oxidized nickel surface

1957 ◽  
Vol 240 (1222) ◽  
pp. 423-436 ◽  
Keyword(s):  
Oxide Film ◽  
Mass Spectrometer ◽  
Rate Constant ◽  
Molecular Beam ◽  
Copper Surface ◽  
Solid Surfaces ◽  
Nickel Surface ◽  
Order Process ◽  
Adsorbed Molecules ◽  
First Order

A method for investigating the lifetimes of adsorbed molecules on solid surfaces is described. A molecular beam of hydrogen was projected on to the surface of a spinning nickel disk, and the hydrogen evaporating from the surface at different times after deposition was collected and measured with a mass spectrometer. On a slightly oxidized nickel surface all the hydrogen was adsorbed. The subsequent evaporation was a first-order process with a rate constant of 4·5 x 10 11 exp ( -11·5 kcal/ RT ) S -1 . With a mixed molecular beam of hydrogen and deuterium no exchange was produced by the adsorption, which is considered to be molecular. Attempts to remove the oxide film from the nickel surface gave an un­stable surface on which no clear results were obtained. The lifetime of hydrogen on a copper surface was too short to measure.

An Electron Spin Resonance Study of Some Reactions of Pentafluorosulfuranyl (SF5)

1975 ◽  
Vol 53 (16) ◽  
pp. 2361-2364 ◽  
Author(s):  
John Charles Tait ◽  
James Anthony Howard
Keyword(s):  
Electron Spin Resonance ◽  
Electron Spin ◽  
Rate Constants ◽  
Arrhenius Equation ◽  
Kinetic Studies ◽  
Electron Spin Resonance Study ◽  
Order Process ◽  
First Order ◽  
Spin Resonance ◽  
Spin Resonance Study

A kinetic electron spin resonance study of the self-reaction of SF5 and a spectroscopic and kinetic e.s.r. study of the reaction of SF5 with 1,1-di-t-butylethylene are reported. This radical undergoes self-reaction by a second-order process and the rate constants are given by the Arrhenius equation log 2k1(M−1 s−1) = (10.3 ± 0.5) − (1.7 ± 0.5)/θ where θ = 2.303RT kcal mol−1. It adds to 1,1-di-t-butylethylene to give (t-Bu)2CCH2SF5 which decomposes by a first-order process with rate constants that obey the expression log k2(s−1) = (13 ± 0.4) − (10 ± 0.2)/θ. Both these rate constants are pertinent to kinetic studies of the photoinduced addition of SF5C1 to olefins.

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