The influence of chloride and other univalent inorganic anions on the visible-absorption spectrum of aspartate aminotransferase.
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ABSTRACT:
SUBMITTER: Bergami M
PROVIDER: S-EPMC1187374 | biostudies-other | 1968 Dec
REPOSITORIES: biostudies-other
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Project description:1. The effect of pH change on the reconstitution of aspartate aminotransferase (EC 2.6.1.1), i.e. the reactivation of the apoenzyme with coenzyme (pyridoxal phosphate and pyridoxamine phosphate), was studied in the pH range 4.2-8.9 by using three buffer systems at concentrations ranging from 0.025 to 0.1m. 2. Although the profile of the reconstitution rate-pH curve in the range pH5.2-6.8 (covered by sodium cacodylate-HCl buffer) reflects the influence of the H(+) concentration on the reconstitution process, the profile of the curve in the pH ranges 4.2-5.6 and 7.2-8.25 (covered respectively by sodium acetate-acetic acid and Tris-HCl buffers) appears to be influenced by the ionic strength of the buffer. 3. The reconstitution is also influenced by univalent inorganic ions such as halide ions and, to a lesser extent, alkali metal ions, which are known to alter the water structure.
| S-EPMC1166105 | biostudies-other
Project description:BackgroundWe aimed to evaluate the association between the aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio and subsequent development of any type of cancer in an apparently healthy population.MethodsWe conducted a retrospective cohort study at St. Luke's International Hospital, Tokyo, Japan between 2005 and 2018. All participants who visited for voluntary health checkups were included. We divided the participants into different quintiles based on the baseline AST/ALT ratios and examined the outcomes.ResultsA total of 85,658 participants were included. The mean age was 44.7 years (standard deviation 12.0) at baseline, and 42,913 (50.1%) of them were men. During a median follow-up of 61.6 months, 4701 (5.5%) participants developed some type of cancer. Compared with the middle AST/ALT ratio group, no other groups had similar adjusted hazard ratios (HR) for the development of any type of cancer in both men and women. When stratified by alcohol consumption, very high (adjusted HR 1.36; 95% CI 1.13-1.63) and high (adjusted HR 1.26; 95% CI 1.05-1.50) AST/ALT ratio groups among men who were regular drinkers had increased adjusted HRs for any type of cancer development, but the very high AST/ALT ratio group among men who were abstainers (adjusted HR 0.64; 95% CI 0.42-0.97) and very low AST/ALT ratio group among men who were occasional drinkers (adjusted HR 0.69; 95% CI 0.48-0.98) had lower adjusted HRs compared with the middle AST/ALT ratio group. Among women, regardless of alcohol consumption, adjusted HR for any type of cancer development was similar across all AST/ALT ratio groups.ConclusionPeople with higher AST/ALT ratios tended to have a higher risk of developing any type of cancer among men who were regular drinkers, but this risk was lower among men who were abstainers. Among women, regardless of alcohol consumption, there was no association between the development of any type of cancer and AST/ALT ratio.
| S-EPMC8817090 | biostudies-literature
Project description:Gene rv3722c of Mycobacterium tuberculosis is essential for in vitro growth, and encodes a putative pyridoxal phosphate-binding protein of unknown function. Here we use metabolomic, genetic and structural approaches to show that Rv3722c is the primary aspartate aminotransferase of M. tuberculosis, and mediates an essential but underrecognized role in metabolism: nitrogen distribution. Rv3722c deficiency leads to virulence attenuation in macrophages and mice. Our results identify aspartate biosynthesis and nitrogen distribution as potential species-selective drug targets in M. tuberculosis.
| S-EPMC7181641 | biostudies-literature
Project description:The functional properties of some biological ion channels and membrane transport proteins are proposed to exploit anion-hydrophobic interactions. Here, we investigate a chloride-pumping rhodopsin as an example of a membrane protein known to contain a defined anion binding site composed predominantly of hydrophobic residues. Using molecular dynamics simulations, we explore Cl- binding to this hydrophobic site and compare the dynamics arising when electronic polarization is neglected (CHARMM36 [c36] fixed-charge force field), included implicitly (via the prosECCo force field), or included explicitly (through the polarizable force field, AMOEBA). Free energy landscapes of Cl- moving out of the binding site and into bulk solution demonstrate that the inclusion of polarization results in stronger ion binding and a second metastable binding site in chloride-pumping rhodopsin. Simulations focused on this hydrophobic binding site also indicate longer binding durations and closer ion proximity when polarization is included. Furthermore, simulations reveal that Cl- within this binding site interacts with an adjacent loop to facilitate rebinding events that are not observed when polarization is neglected. These results demonstrate how the inclusion of polarization can influence the behavior of anions within protein binding sites and can yield results comparable with more accurate and computationally demanding methods.
| S-EPMC10147828 | biostudies-literature
Project description:BackgroundThe prognostic significance of the aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio in hepatocellular carcinoma remains uncertain. The aim of the current study was to evaluate the association between the AST/ALT ratio and prognosis in patients with hepatocellular carcinoma after hepatectomy, and to explore the role of underlying liver diseases as mediators.MethodsThis retrospective study included patients with hepatocellular carcinoma who underwent hepatectomy between January 2014 and January 2018 at two Chinese hospitals. The maximally selected rank statistic and g-computation approach were used to quantify and visualize the association between the AST/ALT ratio and overall survival or recurrence-free survival. The role of mediators (chronic hepatitis B, hepatic steatosis and liver cirrhosis) was analysed.ResultsAmong the 1519 patients (mean(s.d.) age at baseline, 50.5(11.3) years), 1309 (86.2%) were male. During a median follow-up of 46.0 months, 514 (33.8%) patients died and 358 (23.6%) patients experienced recurrence. The optimal cut-off value for the AST/ALT ratio was 1.4, and the AST/ALT ratio greater than or equal to 1.4 was independently associated with a 39.0% increased risk of death and a 30.0% increased risk of recurrence (overall survival: hazard ratio (HR), 1.39; 95% c.i. 1.15 to 1.68; recurrence-free survival: HR, 1.30; 95% c.i. 1.12 to 1.52) after adjusting for confounders. Chronic hepatitis B significantly mediated the association of the ratio of AST/ALT with both overall survival and recurrence-free survival (20.3% for overall survival; 20.1% for recurrence-free survival).ConclusionThe AST/ALT ratio greater than or equal to 1.4 was associated with shorter overall survival and recurrence-free survival in patients with hepatocellular carcinoma after hepatectomy, and chronic hepatitis B may play a role in their association.
| S-EPMC10798825 | biostudies-literature
Project description:The influence of inorganic anions on the photoreactivity and aggregation of titanium dioxide nanoparticles (NPs) was assessed by dosing carbonate, chloride, nitrate, phosphate, and sulfate as potassium salts at multiple concentrations. NP stability was monitored in terms of aggregate morphology and electrophoretic mobility (EPM). Aggregate size and fractal dimension were measured over time by laser diffraction, and the isoelectric point (IEP) as a function of anion and concentration was obtained by measuring EPM versus pH. Phosphate, carbonate, and to a lesser extent, sulfate decreased the IEP of TiO2 and stabilized NP suspensions owing to specific surface interactions, whereas this was not observed for nitrate and chloride. TiO2 NPs were exposed to UV-A radiation, and the photoreactivity was assessed by monitoring the production of reactive species over time both at the NP surface (photogenerated holes) and in the bulk solution (hydroxyl radicals) by observing their reactions with the selective probe compounds iodide and terephthalic acid, respectively. The generation of photogenerated holes and hydroxyl radicals was influenced by each inorganic anion to varying degrees. Carbonate and phosphate inhibited the oxidation of iodide, and this interaction was successfully described by a Langmuir-Hinshelwood mechanism and related to the characteristics of TiO2 aggregates. Chloride and nitrate do not specifically interact with TiO2, and sulfate creates relatively weak interactions with the TiO2 surface such that no decrease in photogenerated hole reactivity was observed. A decrease in hydroxyl radical generation was observed for all inorganic anions. Quenching rate constants for the reaction of hydroxyl radicals with each inorganic anion do not provide a comprehensive explanation for the magnitude of this decrease, which arises from the interplay of several physicochemical phenomena. This work shows that the reactivity of NPs will be strongly influenced by the makeup of the waters they are released into. The impact of anion species on hydroxyl radical inhibition was as follows: carbonate > chloride > phosphate > nitrate > sulfate.
| S-EPMC6471673 | biostudies-literature
Project description:Aspartate aminotransferases have been cloned and expressed from Crithidia fasciculata, Trypanosoma brucei brucei, Giardia intestinalis, and Plasmodium falciparum and have been found to play a role in the final step of methionine regeneration from methylthioadenosine. All five enzymes contain sequence motifs consistent with membership in the Ia subfamily of aminotransferases; the crithidial and giardial enzymes and one trypanosomal enzyme were identified as cytoplasmic aspartate aminotransferases, and the second trypanosomal enzyme was identified as a mitochondrial aspartate aminotransferase. The plasmodial enzyme contained unique sequence substitutions and appears to be highly divergent from the existing members of the Ia subfamily. In addition, the P. falciparum enzyme is the first aminotransferase found to lack the invariant residue G197 (P. K. Mehta, T. I. Hale, and P. Christen, Eur. J. Biochem. 214:549-561, 1993), a feature shared by sequences discovered in P. vivax and P. berghei. All five enzymes were able to catalyze aspartate-ketoglutarate, tyrosine-ketoglutarate, and amino acid-ketomethiobutyrate aminotransfer reactions. In the latter, glutamate, phenylalanine, tyrosine, tryptophan, and histidine were all found to be effective amino donors. The crithidial and trypanosomal cytosolic aminotransferases were also able to catalyze alanine-ketoglutarate and glutamine-ketoglutarate aminotransfer reactions and, in common with the giardial aminotransferase, were able to catalyze the leucine-ketomethiobutyrate aminotransfer reaction. In all cases, the kinetic constants were broadly similar, with the exception of that of the plasmodial enzyme, which catalyzed the transamination of ketomethiobutyrate significantly more slowly than aspartate-ketoglutarate aminotransfer. This result obtained with the recombinant P. falciparum aminotransferase parallels the results seen for total ketomethiobutyrate transamination in malarial homogenates; activity in the latter was much lower than that in homogenates from other organisms. Total ketomethiobutyrate transamination in Trichomonas vaginalis and G. intestinalis homogenates was extensive and involved lysine-ketomethiobutyrate enzyme activity in addition to the aspartate aminotransferase activity. The methionine production in these two species could be inhibited by the amino-oxy compounds canaline and carboxymethoxylamine. Canaline was also found to be an uncompetitive inhibitor of the plasmodial aspartate aminotransferase, with a K(i) of 27 microm.
| S-EPMC95336 | biostudies-literature
Project description:There have been no reports on mortality in patients with markedly elevated aspartate aminotransferase (AST) levels from non-hepatic causes to date. This study aimed to determine the etiologies of markedly elevated AST levels > 400 U/L due to non-hepatic causes and to investigate the factors associated with mortality in these cases. This retrospective study included 430 patients with AST levels > 400 U/L unrelated to liver disease at two centers between January 2010 and December 2021. Patients were classified into three groups according to etiology: skeletal muscle damage, cardiac muscle damage, and hematologic disorder. Binary logistic regression analysis was performed to evaluate the factors associated with 30-day mortality. The most common etiology for markedly elevated AST levels was skeletal muscle damage (54.2%), followed by cardiac muscle damage (39.1%) and hematologic disorder (6.7%). The 30-day mortality rates for the skeletal muscle damage, cardiac muscle damage, and hematologic disorder groups were 14.2%, 19.5%, and 65.5%, respectively. The magnitude of the peak AST level significantly correlated with 30-day mortality, with rates of 12.8%, 26.7%, and 50.0% for peak AST levels < 1000 U/L, <3000 U/L, and ≥3000 U/L, respectively. In the multivariate analysis, cardiac muscle damage (odds ratio [OR] = 2.76, 95% confidence interval [CI] = 1.31-5.80), hematologic disorder (OR = 9.47, 95% CI = 2.95-30.39), peak AST < 3000 U/L (OR = 2.94, 95% CI = 1.36-6.35), and peak AST ≥ 3000 U/L (OR = 9.61, 95% CI = 3.54-26.08) were associated with increased 30-day mortality. Our study revealed three etiologies of markedly elevated AST unrelated to liver disease and showed that etiology and peak AST level significantly affected the survival rate.
| S-EPMC9821092 | biostudies-literature
Project description:Chloride ions are essential for proper function of the photosynthetic oxygen-evolving complex (OEC) of Photosystem II (PS II). Although proposed to be directly ligated to the Mn cluster of the OEC, the specific structural and mechanistic roles of chloride remain unresolved. This study utilizes X-ray absorption spectroscopy (XAS) to characterize the Mn-Cl interaction in inorganic compounds that contain structural motifs similar to those proposed for the OEC. Three sets of model compounds are examined; they possess core structures Mn(IV)(3)O(4)X (X=Cl, F, or OH) that contain a di-micro-oxo and two mono-micro-oxo bridges or Mn(IV)(2)O(2)X (X=Cl, F, OH, OAc) that contain a di-micro-oxo bridge. Each set of compounds is examined for changes in the XAS spectra that are attributable to the replacement of a terminal OH or F ligand, or bridging OAc ligand, by a terminal Cl ligand. The X-ray absorption near edge structure (XANES) shows changes in the spectra on replacement of OH, OAc, or F by Cl ligands that are indicative of the overall charge of the metal atom and are consistent with the electronegativity of the ligand atom. Fourier transforms (FTs) of the extended X-ray absorption fine structure (EXAFS) spectra reveal a feature that is present only in compounds where chloride is directly ligated to Mn. These FT features were simulated using various calculated Mn-X interactions (X=O, N, Cl, F), and the best fits were found when a Mn-Cl interaction at a 2.2-2.3 A bond distance was included. There are very few high-valent Mn halide complexes that have been synthesized, and it is important to make such a comparative study of the XANES and EXAFS spectra because they have the potential for providing information about the possible presence or absence of halide ligation to the Mn cluster in PS II.
| S-EPMC3965209 | biostudies-literature
Project description:BackgroundFew studies discussed the predictive ability of aspartate aminotransferase/alanine aminotransferase (AST/ALT, DeRitis) ratio for diabetes risk. The aim of this study was to characterize the role of AST/ALT ratio in the prediction of Chinese diabetes.MethodsThis retrospective cohort study analyzed a Chinese population comprising 87,883 participants without diabetes at baseline between 2010 and 2016. Cox proportional hazards regression was used to identify independent risk factors. Restricted cubic spline (RCS) was performed to investigate the non-linear correlation between AST/ALT ratio and diabetes risk.ResultsDuring a median follow-up period of 3.01 years, 1,877 participants developed diabetes. Comparing the baseline characteristics, diabetes group exhibited lower AST/ALT ratio. The Kaplan-Meier curve showed that participants with low AST/ALT ratio had higher cumulative incidence, and Cox regression also demonstrated that the lower AST/ALT ratio, the higher diabetes risk (HR: 0.56, 95% CI: 0.37-0.85, P = 0.006). The RCS model revealed a non-linear correlation between AST/ALT ratio and diabetes risk. In the condition of AST/ALT ratio ≤1.18, diabetes risk increased as it decreased (HR: 0.42, 95% CI: 0.19-0.91, P = 0.028). In contrast, AST/ALT ratio did not independently affect diabetes when beyond 1.18.ConclusionAST/ALT ratio is a valuable predictor of diabetes. Diabetes risk increases rapidly in the condition of AST/ALT ratio ≤1.18.
| S-EPMC9666731 | biostudies-literature