The mechanism of the nonenzymatic iodination of tyrosine by molecular iodine

1988 ◽  
Vol 66 (9) ◽  
pp. 967-978 ◽  
Author(s):  
H. Brian Dunford ◽  
Adejare J. Adeniran
Keyword(s):  
Ph Dependence ◽  
Acid Catalyst ◽  
Order Rate Constant ◽  
Molecular Iodine ◽  
Base Catalysis ◽  
Slow Step ◽  
Rate Law ◽  
General Acid ◽  
Phenolic Group ◽  
Ph Range

Over the pH range 7–10, at very low buffer concentration, the nonenzymatic iodination of tyrosine obeys the rate law[Formula: see text]where kapp is the measured second order rate constant based upon the total initial concentrations of molecular iodine and tyrosine and K2 (units M) is the equilibrium constant for [Formula: see text]. The value of k′ is 3.5 × 10−8 M∙s−1. There are three plausible mechanisms that fit the experimental data. One, the simplest, is a concerted process in which hypoiodous acid attacks tyrosine with its phenolic group unionized. The other two involve the formation of an iodinated quinoid reactive intermediate species in a rapid pre-equilibrium between unionized tyrosine and either hypoiodous acid or molecular iodine. The pre-equilibrium, if it occurs, favors the initial reactants. It is followed by a slow step in which the quinoid is converted to mono-iodinated tyrosine. Positive deviations from the rate law for pH dependence indicate that some specific acid catalysis (H3O+) is occurring in the pH range 5–7. In the presence of sufficient buffer, general acid–base catalysis is observed with acetic acid acting as a general acid catalyst in the vicinity of pH 5 and carbonate acting as a general base at pH ~ 9.5. The nonenzymatic iodination of tyrosine occurs more rapidly as the pH is increased, in marked contrast to the peroxidase-catalyzed iodination, which has its optimum at low pH.

scholarly journals Identification of general acid catalyst for the ATPase activity of Lynch syndrome-related MutL homologs

2021 ◽  
Author(s):  
Kenji Fukui ◽  
Yuki Fujii ◽  
Takato Yano
Keyword(s):  
Lynch Syndrome ◽  
Atpase Activity ◽  
Catalytic Mechanism ◽  
Ph Dependence ◽  
Acid Catalyst ◽  
Base Catalysis ◽  
Mechanism Analysis ◽  
Missense Mutations ◽  
Aquifex Aeolicus ◽  
General Acid

Mutations of mismatch repair MutL homologs are causative of a hereditary cancer, Lynch syndrome. Investigation of MutL facilitates genetic diagnoses essential for cancer risk managements and therapies. We characterized MutL homologs from human and a hyperthermophile, Aquifex aeolicus, (aqMutL) to reveal the catalytic mechanism for the ATPase activity. Although existence of a general acid catalyst had not been conceived in the mechanism, analysis of the pH dependence of the aqMutL ATPase activity revealed that the reaction is accelerated by general acid-base catalysis. Analyses of mutant aqMutLs showed that Lys79 is the general acid, and the corresponding residues were confirmed to be critical for activities of human homologs, on the basis of which a catalytic mechanism for MutL ATPase is proposed. These and other results described here would contribute to evaluating the pathogenicity of Lynch syndrome-associated missense mutations.

Oxidation of Nickel(II) and Manganese(II) by Peroxodisulfate in Aqueous Solution in the Presence of Molybdate. Crystal Structure of the (NH4)6[NiMo9O32].6H2O Product

1992 ◽  
Vol 45 (12) ◽  
pp. 1943 ◽  
Author(s):  
SJ Dunne ◽  
RC Burns ◽  
GA Lawrance
Keyword(s):  
Rate Constant ◽  
Linear Dependence ◽  
Ph Dependence ◽  
Order Rate Constant ◽  
X Ray Diffraction ◽  
X Ray ◽  
First Order ◽  
Oxidant Concentration ◽  
Ph Range ◽  
Kinetics Of

Oxidation of Ni2+,aq, by S2O82- to nickel(IV) in the presence of molybdate ion, as in the analogous manganese system, involves the formation of the soluble heteropolymolybdate anion [MMogO32]2- (M = Ni, Mn ). The nickel(IV) product crystallized as (NH4)6 [NiMogO32].6H2O from the reaction mixture in the rhombohedra1 space group R3, a 15.922(1), c 12.406(1) � ; the structure was determined by X-ray diffraction methods, and refined to a residual of 0.025 for 1741 independent 'observed' reflections. The kinetics of the oxidation were examined at 80 C over the pH range 3.0-5.2; a linear dependence on [S2O82-] and a non-linear dependence on l/[H+] were observed. The influence of variation of the Ni/Mo ratio between 1:10 and 1:25 on the observed rate constant was very small at pH 4.5, a result supporting the view that the precursor exists as the known [NiMo6O24H6]4- or a close analogue in solution. The pH dependence of the observed rate constant at a fixed oxidant concentration (0.025 mol dm-3) fits dequately to the expression kobs = kH [H+]/(Ka+[H+]) where kH = 0.0013 dm3 mol-1 s-1 and Ka = 4-0x10-5. The first-order dependence on peroxodisulfate subsequently yields a second-order rate constant of 0.042 dm3 mol-1 s-1. Under analogous conditions, oxidation of manganese(II) occurs eightfold more slowly than oxidation of nickel(II), whereas oxidation of manganese(II) by peroxomonosulfuric acid is 16-fold faster than oxidation by peroxodisulfate under similar conditions.

The reduction of I2 by H2O2 in aqueous solution

2001 ◽  
Vol 79 (3) ◽  
pp. 304-311 ◽  
Author(s):  
J M Ball ◽  
J B Hnatiw
Keyword(s):  
Aqueous Solution ◽  
Hydrogen Peroxide ◽  
Nuclear Reactor ◽  
Ph Dependence ◽  
Radiolysis Product ◽  
Molecular Iodine ◽  
Water Radiolysis ◽  
Reactor Accident ◽  
Rate Law ◽  
Accident Conditions

The reduction of I2 by hydrogen peroxide, a primary water radiolysis product, has been identified as a key reaction that would influence iodine volatility in nuclear reactor accident conditions (1–3). Although there have been a number of studies of the reduction of I2, there exists a great degree of controversy regarding the intermediates involved, the effect of buffers, and the general rate law (1–9). Because the rates and the mechanism of this reaction are important in predicting the pH dependence of iodine behaviour in reactor containment building after a postulated reactor accident, we have undertaken a kinetic study of I2 reduction by H2O2 in aqueous solution over a pH range of 6–9. The experiments were performed using stopped-flow instrumentation and monitoring the decay of I–3 spectrophotometrically. The effects of buffer catalysis have been examined by comparison of kinetic data obtained in sodium barbital (5,5-diethylbarbituric acid), disodium citrate, and disodium hydrogen phosphate buffers. The effect of buffers, combined with the complex acid dependence of the rate law, explains many of the discrepancies reported in earlier literature.Key words: hydrogen peroxide, molecular iodine, kinetics, iodine volatility.

The reaction of 2,4,6-trinitrobenzene sulfonic acid with pancreatic elastase

1970 ◽  
Vol 48 (11) ◽  
pp. 1249-1259 ◽  
Author(s):  
Leticia Rao ◽  
T. Hofmann
Keyword(s):  
Rate Constant ◽  
Sulfonic Acid ◽  
Ph Dependence ◽  
Order Rate Constant ◽  
Trinitrobenzene Sulfonic Acid ◽  
Amino Group ◽  
Tyrosine Residues ◽  
Inactivation Rate Constant ◽  
Lysine Residues ◽  
Ph Range

The reaction of elastase with trinitrobenzene sulfonic acid was investigated in the pH range 9–12. Elastase was found to be inactivated by 2,4,6-trinitrobenzene sulfonic acid. The pH dependence of the pseudo first-order inactivation rate constant showed a pK of 10.3 and gave a Hill plot coefficient of 1.15. Trinitrophenol did not inactivate the enzyme. These results indicate that the inactivation is due to the covalent reaction of trinitrobenzene sulfonic acid with a single group in the enzyme. This group is not the N-terminal since the loss of N-terminal valine was considerably slower than the loss of activity at pH 10.5. The inactivation of elastase with 2,4-dinitrofluorobenzene also showed no correlation with the loss of the N-terminal. When the enzyme was exhaustively treated and fully inactivated with trinitrobenzene sulfonic acid at pH 10.5, the N-terminal valine and two out of three lysine residues were trinitrophenylated. No evidence for the loss of histidine was found. One of the tyrosine residues may be trinitrophenylated as judged from the molar extinction of the trinitrophenylated protein, but it has not been possible to isolate a trinitrophenylated tyrosine-containing peptide. The results can be interpreted in one of two ways: (a) trinitrophenylation of a group with a pK of 10.3, not involved in the activity, inactivates because the introduction of the trinitrophenyl residue causes a denaturation of the enzyme; or (b) a group with a pK of 10.3 controls the active conformation of the enzyme. The results do not exclude the possibility that the N-terminal plays an important role in the activity of the enzyme. Below pH 10.5 the reactivity of the N-terminal is low, indicating that it is buried.At pH 9.0 only the ε-amino group of lysine in position 224 reacted with trinitrobenzene sulfonic acid and full activity was retained. The second-order rate constant for the trinitrophenylation of this group was 25 times higher than that of the ε-amino group of the α-N-benzoyllysine.

Studies on Horseradish Peroxidase. VII. A Kinetic Study of the Oxidation of Iodide by Horseradish Peroxidase Compound II

1971 ◽  
Vol 49 (18) ◽  
pp. 3059-3063 ◽  
Author(s):  
R. Roman ◽  
H. B. Dunford ◽  
M. Evett
Keyword(s):  
Ionic Strength ◽  
Horseradish Peroxidase ◽  
Kinetic Study ◽  
Rate Constant ◽  
Ph Dependence ◽  
Order Rate Constant ◽  
Acid Dissociation ◽  
Ph Range ◽  
Compound Ii ◽  
Kinetics Of

The kinetics of the oxidation of iodide ion by horseradish peroxidase compound II have been studied as a function of pH at 25° and ionic strength of 0.11. The logarithm of the second-order rate constant decreases linearly from 2.3 × 105 to 0.1 M−1 s−1 with increasing pH over the pH range 2.7 to 9.0. The pH dependence of the reaction is explained in terms of an acid dissociation outside the pH range of the study.

scholarly journals pH-dependence and structure–activity relationships in the papain-catalysed hydrolysis of anilides

1971 ◽  
Vol 124 (1) ◽  
pp. 117-122 ◽  
Author(s):  
G. Lowe ◽  
Y. Yuthavong
Keyword(s):  
Acid Catalysis ◽  
Ph Dependence ◽  
Base Catalysis ◽  
General Base ◽  
Structure Activity ◽  
Equilibrium Binding ◽  
General Acid ◽  
Leaving Group ◽  
Hydrolysis Of ◽  
Equilibrium Binding Constant

The pH-dependence of the Michaelis–Menten parameters for the papain-catalysed hydrolysis of N-acetyl-l-phenylalanylglycine p-nitroanilide was determined. The equilibrium binding constant, Ks, is independent of pH between 3.7 and 9.3, whereas the acylation constant, k+2, shows bell-shaped pH-dependence with apparent pKa values of 4.2 and 8.2. The effect of substituents in the leaving group on the acylation constant of the papain-catalysed hydrolysis of hippuryl anilides and N-acetyl-l-phenylalanylglycine anilides gives rise in both series to a Hammett ρ value of -1.04. This indicates that the enzyme provides electrophilic, probably general-acid, catalysis, as well as the nucleophilic or general-base catalysis previously found. A mechanism involving a tetrahedral intermediate whose formation is general-base-catalysed and whose breakdown is general-acid-catalysed seems most likely. The similarity of the Hammett ρ values appears to exclude facilitated proton transfer as a means through which the specificity of papain is expressed.

scholarly journals Reactions of l-ergothioneine and some other aminothiones with 2,2′- and 4,4′-dipyridyl disulphides and of l-ergothioneine with iodoacetamide. 2-Mercaptoimidazoles, 2- and 4-thiopyridones, thiourea and thioacetamide as highly reactive neutral sulphur nucleophiles

1974 ◽  
Vol 139 (1) ◽  
pp. 221-235 ◽  
Author(s):  
Jan Carlsson ◽  
Marek P. J. Kierstan ◽  
Keith Brocklehurst
Keyword(s):  
Transition State ◽  
Isotope Effect ◽  
Rate Constant ◽  
Order Rate Constant ◽  
Base Catalysis ◽  
The Other ◽  
Deuterium Isotope Effect ◽  
General Base ◽  
Nucleophilic Reactivity ◽  
Ph Range

1. The reactions of 2,2′- and 4,4′-dipyridyl disulphide (2-Py–S–S–2-Py and 4-Py–S–S–4-Py) with l-ergothioneine (2-mercapto-l-histidine betaine), 2-mercaptoimidazole, 1-methyl-2-mercaptoimidazole, thiourea, thioacetamide, 2-thiopyridone (Py–2-SH) and 4-thiopyridone (Py–4-SH) were investigated spectrophotometrically in the pH range approx. 1–9. 2. These reactions involve two sequential reversible thiol–disulphide interchanges. 3. The reaction of l-ergothioneine with 2-Py–S–S–2-Py and/or with the l-ergothioneine–Py–2-SH mixed disulphide, both of which provide Py–2-SH, is characterized by at least three reactive protonic states. This provides definitive evidence that neutral l-ergothioneine is a reactive nucleophile, particularly towards the highly electrophilic protonated disulphides. 4. A similar situation appears to obtain in the reactions of l-ergothioneine and Py–2-SH with 4-Py–S–S–4-Py and in the reactions of the other 2-mercaptoimidazoles, thiourea and Py–4-SH with 2-Py–S–S–2-Py. The nucleophilic reactivity of Py–4-SH suggests that general base catalysis provided by the disulphide in a cyclic or quasi-cyclic transition state is not necessary to generate nucleophilic reactivity in the other amino-thiones whose geometry could permit such catalysis. 5. The existence of a positive deuterium isotope effect in the l-ergothioneine–2-Py–S–S–2-Py system at pH6–7 provides no evidence for general base catalysis but is in accord with a mechanism involving specific acid catalysis and post-transition-state proton transfer. 6. The pH-dependences of the overall equilibrium positions of the various thiol–disulphide interchanges are described. 7. Reaction of thioacetamide with a stoicheiometric quantity of 2-Py–S–S–2-Py at pH1 provides 2 molecules of Py–2-SH per molecule of thioacetamide and elemental sulphur; these findings can be accounted for by thiol–disulphide interchange to provide a thioacetamide–Py–2-SH mixed disulphide followed by fragmentation to provide CH3CN, S and Py–2-SH. 8. Provision of high reactivity in the neutral forms of the members of this series of sulphur nucleophiles by electron donation by the amino group is compared with the well known α effect that provides enhanced nucleophilicity in compounds containing an electronegative atom adjacent to the nucleophilic atom. 9. The decrease in the u.v. absorption of l-ergothioneine at 257nm consequent on transformation of its aminothione moiety into an S-alkyl-2-mercaptoimidazole moiety provides a convenient method of following the alkylation of l-ergothioneine by iodoacetamide. 10. The pH dependence of the extinction coefficient of l-ergothioneine at 257nm is described by ε257={8×103/(1+Ka/[H+]} +6×103m−1·cm−1 in which pKa=10.8. 11. In the pH range 3–11 the reaction is characterized by two reactive protonic states (X and XH). 12. The X state, reaction of the ionized 2-mercaptoimidazole moiety of the l-ergothioneine dianion with neutral iodoacetamide, is characterized by the second-order rate constant 4.0m−1·s−1 (25.0°C, I=0.05). The XH state, characterized by the second-order rate constant 0.03m−1·s−1, is interpreted as reaction of the thione form of the neutral 2-mercaptoimidazole moiety of the l-ergothioneine monoanion with neutral iodoacetamide. 13. The XH state of the alkylation reaction does not exhibit a deuterium isotope effect.

Horseradish peroxidase. XXXII. pH dependence of the oxidation of L-(−)-tyrosine by compound I

1978 ◽  
Vol 56 (12) ◽  
pp. 1115-1119 ◽  
Author(s):  
I. Ralston ◽  
H. B. Dunford
Keyword(s):  
Horseradish Peroxidase ◽  
Ph Dependence ◽  
Nonlinear Least Squares ◽  
Compound I ◽  
Ph Profile ◽  
Rate Versus ◽  
Tyrosine Oxidation ◽  
Phenolic Group ◽  
Ph Range ◽  
Single Enzyme

The rate of oxidation of L-(−)-tyrosine by horseradish peroxidase compound I has been studied as a function of pH at 25 °C and ionic strength 0.11. Over the pH range of 3.20–11.23 major effects of three ionizations were observed. The pKa values of the phenolic (pKa = 10.10) and amino (pKa = 9.21) dissociations of tyrosine and a single enzyme ionization (pKa = 5.42) were determined from nonlinear least squares analysis of the log rate versus pH profile. It was noted that the less acidic form of the enzyme was most reactive; hence, the reaction is described as base catalyzed. The rate of tyrosine oxidation falls rapidly with the deprotonation of the phenolic group.

Electroanalytical chemistry of vanadium complexes: Electrochemical oxidation of [V(IV)O(nta)(H2O)]-

1989 ◽  
Vol 54 (1) ◽  
pp. 64-69 ◽  
Author(s):  
Roland Meier ◽  
Gerhard Werner ◽  
Matthias Otto
Keyword(s):  
Cyclic Voltammetry ◽  
Electrochemical Oxidation ◽  
Ph Dependence ◽  
Differential Pulse ◽  
Nitrilotriacetic Acid ◽  
Reduced Form ◽  
Vanadium Complexes ◽  
Differential Pulse Polarography ◽  
Electroanalytical Chemistry ◽  
Ph Range

Electrochemical oxidation of [V(IV)O(nta)(H2O)]- (H3nta nitrilotriacetic acid) was studied in aqueous solution by means of cyclic voltammetry, differential pulse polarography, and current sampled DC polarography on mercury as electrode material. In the pH-range under study (5.5-9.0) the corresponding V(V) complex is produced by one-electron oxidation of the parent V(IV) species. The oxidation product is stable within the time scale of cyclic voltammetry. The evaluation of the pH-dependence of the half-wave potentials leads to a pKa value for [V(IV)O(nta)(H2O)]- which is in a good agreement with previous determinations. The measured value for E1/2 is very close to the formal potential E0 calculated via the Nernst equation on the basis of known literature values for log Kox and log Kred, the complex stability constants for the oxidized and reduced form, respectively.

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