Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Protons”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 307 records · Page 17Linked to original sources
PubMed1983

Proton nuclear magnetic resonance study of the dynamic stability of the heme pocket of soybean leghemoglobin a. Exchange rates for the labile proton of the proximal histidyl imidazole.

Intrinsic spin lattice relaxation times for the hyperfine-shifted exchangeable resonances and the downfield heme methyls for the low spin met-cyano-, met-nicotinate-, and deoxy- complexes of soybean leghemoglobin a were determined in H2O. When exchange with the bulk solvent is slow on the T1 time scale, comparison of the intrinsic T1 values for the exchangeable protons and the heme methyl resonances has provided the assignment of the proximal histidyl imidazole N1H proton resonance. Transfer of saturation experiments and linewidth data as a function of pH at 25 degrees C permitted the determination of the proximal histidyl imidazole N1H exchange rates in various protein oxidation/ligation states. The exchange rates were found to be base-catalyzed in the deoxy- as well as the met-cyano-, met-nicotinate-, and met-azide- complexes. The exchange rates are taken as measures of the magnitude of the fluctuations of the protein conformation near the heme cavity. The unligated deoxy-protein exhibited a greater kinetic stability than ligated forms of the protein, and the bulky nicotinate ligand resulted in the lowest kinetic stability for the ligated protein forms. In contrast to met-cyanomyoglobin, no resonance which could be attributed to the distal histidyl imidazole NH was observed for any of the low spin complexes of leghemoglobin. Comparison between the same form of leghemoglobin and myoglobin reveals that the former exhibits exchange rates an order of magnitude faster than the latter protein in both ligated and unligated states, confirming the greater flexibility of the heme pocket in leghemoglobin.

Heme↗
PubMed1981

Proton gradients in renal cortex brush-border membrane vesicles. Demonstration of a rheogenic proton flux with acridine orange.

The fluorescence quenching of acridine orange has been used to study the formation and dissipation of acid interior pH gradients in brush-border membrane vesicles from rabbit renal cortex. Acidic interior pH gradients were produced by 1) outwardly directed gradients of Na+ or K+, and 2) the addition of vesicles equilibrated at pH 6.0 to 7.5 buffer. The rate of pH gradient dissipation was stimulated 6.3-fold by the replacement of tetramethylammonium gluconate by tetramethylammonium chloride. A further increase, of 2-fold, was seen upon the addition of carbonyl cyanide-m-chlorophenylhydrazine, demonstrating the existence of a Cl- conductance pathway. In the presence of valinomycin, the replacement of tetramethylammonium gluconate by K gluconate increased the rate of delta pH dissipation by 11-fold, demonstrating the existence of a conductive pathway for protons. This pathway for protons was also shown by the formation of an acidic interior space by an outwardly directed K gradient in the presence of valinomycin. The parallel conductive pathways for H+ and Cl- may dissipate pH and chloride gradients across the luminal membrane of the proximal tubule.

Acridine Orange↗
PubMedDate not supplied

Novel, delta-opioid receptor-selective peptide antagonists: demonstration of a possible opioid interaction in the absence of a protonated nitrogen and attempts to locate the protonated nitrogen site.

We have recently (Rónai et al., 1992) introduced a family of novel delta-opioid receptor-selective peptide antagonists, based on the Tyr-Pro-Gly-Phe-Leu-Thr structure, where the nitrogen accepts substituents that make protonation possible (e.g. diallyl) as well as substituents (e.g. t-Boc) where protonation cannot occur. In this paper, we present the details of a design strategy where the structurally closely related biologically active and inactive compounds are suggestive of conformational requirements of action. Furthermore, since even those derivatives of the antagonist peptides where the N-terminus was free were either devoid of opioid agonist activity or were extremely weak agonists, it is suggested that these antagonists do not interact with the conventional "opioid nitrogen site". To find this "conventional" site, a number of N-substituted (phenylglycyl-, alpha-Boc-lysyl-, alpha-Phe-beta-alanyl-) derivatives of Tyr-Pro-Gly-Phe-Leu-Thr hexapeptide were synthesized and their biological activities were determined in the mouse vas deferens bioassay.

Amino Acid Sequence↗
PubMed2003

Interactions between NADPH oxidase and voltage-gated proton channels: why electron transport depends on proton transport.

Leukocytes kill microbes by producing reactive oxygen species, using a multi-component enzyme complex, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Electrons pass from intracellular NADPH through a redox chain within the enzyme, to reduce extracellular O2 to O2-. Electron flux is electrogenic, and rapidly depolarizes the membrane potential. Excessive depolarization can turn off electron transport by self-inhibition, but this is prevented by proton flux that balances the electron flux. Although the membrane potential depolarizes by approximately 100 mV during the respiratory burst (NADPH oxidase activity), NADPH oxidase activity is independent of voltage in this range, which permits optimal function and prevents self-inhibition.

Animals↗
PubMed1999

Comment on the use of GOES solar proton data and spectra in solar proton dose calculations.

There is a need to understand the calibration and response of the GOES solar particle detectors since the GOES data are being used to evaluate high energy solar particle events. We share some of our experience in utilizing these data in the analysis of solar particle ground-level events (GLEs). For the 29 September 1989 event, we have evaluated the solar proton and alpha particle spectral characteristics throughout the event. The results show that the solar cosmic ray spectrum is extremely hard at low energies with the magnitude of the slope increasing with increasing energy and with time.

Alpha Particles↗
PubMed2003

Synthesis, characterization, inequivalency of methylene proton and proton lability in the amino ligand of trans-[dichloro[(N-ferrocenyl methyl)amine](eta2-ethene)platinum] complexes.

A series of complexes of the type trans-[PtCl(2)(eta(2)-ethene)(N-ferrocenyl methyl)amine)] complexes, N-ferrocenylmethylamine=[(eta(5)-C(5)-H(5))Fe(eta(5)-C(5)-H(4)CH(2)NHR], R=(Me, Pr(i), Bu(s), Bu(t), CH(2)Ph, (p-OCH(3))Ph, (o-(OCH(3))Ph, (p-CH(3))Ph, (o-CH(3))Ph, (m-CH(3))Ph, (p-Cl)Ph) have been synthesized and characterized on the basis of elemental analysis, IR, 1H and 13C NMR spectroscopic methods. The CpCH(2)NHR (Cp=(eta(5)-C(5)H(5))Fe(eta(5)-C(5)H(4)), region of the 1H NMR spectrum of the complexes has been investigated and shown to contain inequivalent methylene protons, NH-CH and 195Pt-N-CH coupling take place.

Carbon↗
PubMed1991

Mechanism of proton pumping in bacteriorhodopsin by solid-state NMR: the protonation state of tyrosine in the light-adapted and M states.

Solid-state 13C NMR spectra were employed to characterize the protonation state of tyrosine in the light-adapted (bR568) and M states of bacteriorhodopsin (bR). Difference spectra (isotopically labeled bR minus natural-abundance bR) were obtained for [4'-13C]Tyr-labeled bR, regenerated with [14-13C]retinal as an internal marker to identify the photocycle states. The [14-13C]retinal has distinct chemical shifts for bR555, for bR568, and for the M intermediate generated and thermally trapped at pH 10 in the presence of 0.3 M KCl or 0.5 M guanidine. Previous work has demonstrated that tyrosine and tyrosinate are easily distinguished on the basis of the chemical shift of the 4'-13C label and that both NMR signals are detectable in dark-adapted bR, although the tyrosinate signal is only present at pH values greater than 12. In the present work, we show that neither the light-adapted form of bR prepared at pH 7 or 10 nor the M state thermally trapped at -80 degrees C in 0.3 M KCl pH 10, or in 0.5 M guanidine pH 10, shows any detectable tyrosinate. In addition, after the M samples were briefly warmed (approximately 30 s), no tyrosinate was observed. However, small (1-2 ppm) changes in the structure or dispersion in the Tyr peak were observed in the M state phototrapped by either method. These changes were reversible when the sample was warmed, although on a time scale slower than the relaxation of the retinal back to the bR568 conformer.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacteriorhodopsins↗
PubMed1998

Proton transfer in benzyl alcohol dehydrogenase during catalysis: alternate proton-relay routes.

His51 in horse liver alcohol dehydrogenase (ADHE) has been proposed to act as a proton donor/acceptor in the NAD+/NADH-dependent oxidation/reduction of alcohol/aldehyde. The residue corresponding to His51 of ADHE is Val51 (Val45 in the protein sequence) in benzyl alcohol dehydrogenase (BADH) encoded by TOL plasmid pWW0. The 3-D structure of BADH modeled from the crystal structure of ADHE suggests that His47 (His41 in the protein sequence, corresponding to Arg47 in ADHE) of BADH would play the role of His51 in ADHE. To test this hypothesis, mutants of BADH, in which His47 was replaced by Gln(His47Gln) and/or Val51 was replaced by His (Val51His), were constructed. The kcat/K(m) value of the His47Gln mutant for benzyl alcohol was 125-fold lower than that of wild-type BADH, while the kcat/K(m) value of the His47Gln/Val51His double mutant was 12-fold higher than that of the His47Gln mutant. The kcat/K(m) value of the His47Gln mutant increased with increasing concentration of exogenous amines. These results suggest that His47 in wild-type BADH, exogenous amines in the His47Gln mutant, and His51 in the double mutant act as a general base catalyst during alcohol oxidation.

Alcohol Oxidoreductases↗
PubMed1981

Evidence that the lack of high catalytic activity of thiolsubtilisin towards specific substrates may be due to an inappropriately located proton-distribution system. Demonstration of highly nucleophilic character of the thiol group of thiolsubtilisin in the catalytically relevant ionization state of the active centre by use of a two-protonic-state reactivity probe.

The active centre of the semi-synthetic enzyme thiolsubtilisin was investigated by studying the kinetics of the reaction of the thiol group of cysteine-221 with the thiol-specific two-protonic-state reactivity probe 2,2'-dipyridyl disulphide. The three-states criterion [Brocklehurst (1974) Tetrahedron 30, 2397-2407] was used to provide definitive evidence of the existence of a thiol--imidazole interactive system in acidic media in which the sulphur atom possesses highly nucleophilic character. The lack of catalytic competence of thiolsubtilisin despite its possession of the requisite nucleophilic capability is discussed. The exceedingly high rate of reaction of thiolsubtilisin with 2,2'-dipyridyl disulphide at pH 4--5 is shown to constitute a rapid and convenient active-site titration in which intact thiol--imidazole interaction is detected even in the presence of other thiols.

2,2'-Dipyridyl↗
PubMed1984

Proton translocating ATPase in lysosomal membrane ghosts. Evidence that alkaline Mg2+-ATPase acts as a proton pump.

Membrane ghosts were prepared from purified lysosomes (tritosomes) of rat liver by hypo-osmotic treatment. Mg2+-ATP-driven acidification was observed in the membrane ghosts using acridine orange as a fluorescent probe of the transmembrane pH gradient (delta pH). Its properties were the same as those of intact lysosomes reported previously (Ohkuma, S., Moriyama, Y., & Takano, T. (1982) Proc. Natl. Acad. Sci. U.S. 79, 2758-2762; Moriyama, Y., Takano, T., & Ohkuma, S. (1982) J. Biochem. 92, 1333-1336). The H+-pump was found to be electrogenic with use of bis(3-phenyl-5-oxoisoxasol-4-yl)pentamethine oxonol as a fluorescent membrane potential probe. Alkaline Mg2+-ATPase activity was also identified on the membranes. It showed a pH maximum of pH 8.0-8.5, a Km value for ATP of 0.36 mM and a Vmax of 0.41 units/mg protein at 30 degrees C. Its activity was inhibited by dicyclohexylcarbodiimide, tri-n-butyltin, azide and ADP, but not by ouabain or vanadate. It differed from mitochondrial F1F0-ATPase in sensitivities to N-ethylmaleimide, 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole, quercetin, and oligomycin. Since this alkaline Mg2+-ATPase activity is very similar to the H+-pump activity in its requirement for divalent cations, substrate specificity and sensitivities to various chemicals, it may act as a proton translocase (H+-pump). Possible mechanisms of action of some chemicals, such as 4-acetamide-4'-isothiocyanatostilbene-2,2'-disulfonic acid, that inhibited the H+-pump but not the alkaline Mg2+-ATPase, are discussed.

4-Chloro-7-nitrobenzofurazan↗
PubMed2005

Validation of a short questionnaire in English and French for use in patients with persistent upper gastrointestinal symptoms despite proton pump inhibitor therapy: the PASS (Proton pump inhibitor Acid Suppression Symptom) test.

BACKGROUND: The management of persistent symptoms during acid suppression therapy in patients with gastroesophageal reflux disease or dyspepsia might be improved if patient-physician communication regarding the presence and character of these persistent symptoms were facilitated. AIM: To validate a short, simple questionnaire (the Proton pump inhibitor [PPI] Acid Suppression Symptom [PASS] test), in English and French, to identify patients with persistent acid-related symptoms during PPI therapy and document their response to a change in therapy. METHODS: Patients with persistent acid-related symptoms on PPI therapy were interviewed to produce a draft, five-item questionnaire; content validity was evaluated by focus groups comprising English- and French-speaking patients. Psychometric validity was subsequently evaluated in a multicentre, family practice-based study of English- and French-speaking patients with persistent acid-related upper gastrointestinal symptoms despite PPI therapy. The PASS test, Global Overall Symptom scale, Gastrointestinal Symptom Rating Scale (GSRS), Quality of Life in Reflux and Dyspepsia questionnaire and Reflux Disease Questionnaire were completed at baseline and repeated after one week while patients continued their original PPI therapy. All patients then received esomeprazole 40 mg once daily for four weeks, after which all questionnaires and an evaluation of overall treatment effect were completed. RESULTS: Content validity was established in 20 English- and 16 French-speaking patients. Psychometric validation in 158 English- and 113 French-speaking patients revealed good-to-excellent test-retest reliability coefficients: 0.76 for English; 0.68 for French. For construct validity, the PASS test showed moderate-to-high correlation with the GSRS scale (0.51 for English; 0.43 for French). After four weeks of therapy, the PASS test score fell to zero in 30% of English- and 33% of French-speaking patients, while the Global Overall Symptom score fell to one (no symptoms) in 32% of patients (English- and French-speaking); the PASS test demonstrated good responsiveness in comparison with the GSRS, Reflux Disease Questionnaire and Quality of Life in Reflux and Dyspepsia questionnaire. CONCLUSION: The five-item PASS test is a valid tool for the evaluation of persistent acid-related symptoms in patients receiving PPI therapy. It demonstrates good content validity, test-retest reliability, responsiveness and construct validity in both English and French forms. The PASS test is a simple, clinically applicable tool for the identification of patients with persistent acid-related symptoms during therapy and the assessment of their responses to a change in therapy.

Dyspepsia↗
PubMed1989

Proton magnetic resonance spectroscopy of plasma from patients with dyslipoproteinemia: identification of factors governing methyl and methylene proton line widths.

The line width of the proton magnetic resonance spectrum (MRS) of the composite methylene and methyl resonances of plasma has been reported as a marker for the presence of malignancy. In this study, the contribution of very low density (VLDL), low density (LDL), and high density lipoproteins (HDL) to the MRS line width was determined. This was achieved by measuring the MRS line widths for the plasma from patients with primary disorders of lipoprotein metabolism and from normal individuals. A negative correlation between plasma trigylceride levels and the average line width was observed and this was confirmed in normal plasma to which pure VLDL was added. Also, computer simulations were employed to demonstrate how the line width varies in such complex mixtures of lipoproteins. We demonstrate that the line width is governed by the relative contribution of VLDL and HDL to the composite line shape. This is particularly important when the shoulder from the HDL line lies near the half-height of the VLDL line. As changes in VLDL/HDL ratio occur in patients with malignancy, we propose that this is the basis of the narrowed MRS lines observed in the proposed test for malignancy. However, any individual with elevated VLDL will be false positive in this test.

Centrifugation, Density Gradient↗
PubMed2000

Entropy-driven hydrogen bonding: stereodynamics of a protonated, N,N-chiral "proton sponge".

The C2-symmetric ("[DL]") and achiral ("[meso]") diastereoisomers of the hydrogen iodide salt of 1,8-bis-(N-benzyl-N-methylamino)naphthalene ([2H]-[I] ) interconvert in solution. Direct interconversion of the diastereoisomers of [2H]+ must involve hydrogen bond fission (to give "[nonHB-2H+]") and rotation-inversion of the non-protonated nitrogen centre. The global activation parameters (deltaH++ and deltaS++) for diastereoisomer interconversion in [D7]DMF have been determined from rate data obtained by temperature-drop and magnetisation-transfer 13C NMR spectroscopy over a temperature range of 170 degrees C. The process is found to have a high entropy of activation in both directions (deltaS++=163(+/-4) and 169(+/-4) JK(-1)mol(-1)) and this is suggested to arise through hydrogen bonding of the ammonium centre in [nonHB-2H+] with the solvent ([D7]DMF). Comparison of the enthalpy of activation (deltaH++) with that earlier found for diastereoisomer interconversion of the free-base form 2 suggests that the intramolecular hydrogen bond in [2H]+ is roughly equal in enthalpic strength (deltaH) with that made with the solvent ([D7]DMF) in the non-hydrogen-bonded intermediate [nonHB-2H+]. As such, the hydrogen bonding in [2H]+ may be considered as predominantly an entropically driven process, without any unusual enthalpic strength.

Journal Article↗
PubMed2006

New insights into the mechanism of proton transfer to hydride complexes: kinetic and theoretical evidence showing the existence of competitive pathways for protonation of the cluster [W3S4H3(dmpe)3]+ with acids.

The reaction of the hydride cluster [W3S4H3(dmpe)3]+ (1, dmpe = 1,2-bis(dimethylphosphanyl)ethane) with acids (HCl, CF3COOH, HBF4) in CH2Cl2 solution under pseudo-first-order conditions of excess acid occurs with three kinetically distinguishable steps that can be interpreted as corresponding to successive formal substitution processes of the coordinated hydrides by the anion of the acid (HCl, CF3COOH) or the solvent (HBF4). Whereas the rate law for the third step changes with the nature of the acid, the first two kinetic steps always show a second-order dependence on acid concentration. In contrast, a single kinetic step with a first-order dependence with respect to the acid is observed when the experiments are carried out with a deficit of acid. The decrease in the T1 values for the hydride NMR signal of 1 in the presence of added HCl suggests the formation of an adduct with a W-H...H-Cl dihydrogen bond. Theoretical calculations for the reaction with HCl indicate that the kinetic results in CH2Cl2 solution can be interpreted on the basis of a mechanism with two competitive pathways. One of the pathways consists of direct proton transfer within the W-H...H-Cl adduct to form W-Cl and H2, whereas the other requires the presence of a second HCl molecule to form a W-H...H-Cl...H-Cl adduct that transforms into W-Cl, H2 and HCl in the rate-determining step. The activation barriers and the structures of the transition states for both pathways were also calculated, and the results indicate that both pathways can be competitive and that the transition states can be described in both cases as a dihydrogen complex hydrogen-bonded to Cl- or HCl2(-).

Journal Article↗
PubMed2000

Direct refinement against proton-proton dipolar couplings in NMR structure determination of macromolecules.

The computational tools necessary for making use of (1)H-(1)H dipolar couplings in macromolecular structure refinement are presented. Potentials are described for direct refinement against (1)H-(1)H dipolar couplings of known sign as well as of unknown sign. In addition, a multiple potential is developed for prochiral protons whose stereospecific assignments are unknown. The utility of direct (1)H-(1)H dipolar coupling refinement is illustrated using the small protein ubiquitin. It is shown that direct (1)H-(1)H dipolar coupling refinement leads to improvements in the precision, accuracy, and quality of the resulting structures.

Macromolecular Substances↗
PubMed1994

An evaluation of least-squares fits to COSY spectra as a means of estimating proton-proton coupling constants. I. Simulated test problems.

A computational method is described that takes an initial estimate of the chemical shifts, line widths and scalar coupling constants for the protons in a molecule, and refines this estimate so as to improve the least-squares fit between an experimental COSY spectrum and the spectrum simulated from these parameters in the weak-coupling approximation. In order to evaluate the potential of such refinements for estimating these parameters from COSY experiments, the method has been applied to a large number of sample problems which were themselves simulated from standard conformations of the amino acids, along with 25 near-native conformations of the protein bovine pancreatic trypsin inhibitor. The results of this evaluation show that: (i) if the chemical shifts are known to within ca. 0.01 ppm and no noise or artifacts are present in the data, the method is capable of recovering the correct coupling constants, starting from essentially arbitrary values, to within 0.1 Hz in almost all cases. (ii) Although the precision of these estimates of the coupling constants is degraded by the limited resolution, noise and artifacts present in most experimental spectra, the large majority of coupling constants can still be recovered to within 1.0 Hz; the local minimum problem is not made significantly worse by such defects in the data. (iii) The method assigns an 'effective' line width to all the resonances, and in the process can resolve overlapping cross peaks. (iv) The method is not capable of determining the chemical shifts a priori, due to the presence of numerous local minima in the least-squares residual as a function of these parameters.

Computer Simulation↗
PubMed1987

Proton relaxation time of immature brain. I. Measurement of proton relaxation time (T1 and T2) in immature rat brain by 1H-NMR spectroscopy.

It is generally accepted that the water content in the brain tissue of immature animals is so great as to be responsible for the prolongation of proton relaxation time, namely, the spin-lattice relaxation time (T1) and the spin-spin relaxation time (T2). In assessing edema in the immature rat brain with the passage of time, we measured the water content, T1, and T2, and then compared these parameters with those in rats aged 5 weeks. Traumatic cerebral edema was experimentally produced in immature rats aged 7 days (group A) and mature rats aged 5 weeks (group B). In group A, the water content of the gray matter and the white matter increased significantly on the 1st day after the development of experimental brain edema, continued at a high level in white matter, but normalized in gray matter on the 7th day. On the other hand, for group B, the water content of gray and white matter also increased significantly 1 day after the production of the brain edema, but was reduced to within the normal range on the 7th day for both regions.

Age Factors↗