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N-(carboxymethyl)valine residues in hemoglobin (CMV-Hb) reflect accumulation of oxidative stress in diabetic patients.

While carboxymethylated proteins are considered to be advanced glycation end products (AGE), they can also be induced by reactive oxygen species (ROS) independently of the AGE-forming process. To clarify whether N-(carboxymethyl)valine residues in hemoglobin (CMV-Hb) were a useful marker of the accumulation of ROS in diabetes, we evaluated CMV-Hb formation in vitro and in vivo. For the in vitro studying, purified human hemoglobin was incubated with D-glucose or D-glucose and hydrogen peroxide. For the in vivo study, CMV-Hb was extracted from peripheral red blood cells in diabetic patients and compared with that from non-diabetic subjects. Furthermore, the effect of antioxidants was evaluated after 6 months in 15 diabetic patients showing very high CMV-Hb levels. In vitro CMV-Hb formation increased in a glucose concentration and time-dependent manner. Co-incubation with glucose and hydrogen peroxide synergistically increased CMV-Hb formation. The CMV-Hb level was higher in the diabetic group than the non-diabetic group, and CMV-Hb was correlated with the plasma total cholesterol and serum creatinine levels. The CMV-Hb level was decreased by antioxidant therapy, whereas HbA1c did not change. These results demonstrate that CMV-Hb may be a useful marker for accumulation of oxidative stress in diabetic patients.

Diabetes Mellitus, Type 2↗

A pharmacogenetic effect of factor XIII valine 34 leucine polymorphism on fibrinolytic therapy for acute myocardial infarction.

OBJECTIVES: The aim of this study was to evaluate the pharmacogenetic role of the factor XIII (FXIII) valine 34 leucine (Val34Leu) polymorphism in the fibrinolytic therapy of acute myocardial infarction (MI). BACKGROUND: Fibrinolytic therapy is an established treatment for acute MI, but up to 40% of treated patients do not achieve optimal tissue reperfusion. The FXIII Val34Leu polymorphism is one of the most relevant functional polymorphisms described in the haemostatic system. The common Leu34 allele associates with an increased FXIII-transglutaminase activity, which results in an increased and faster rate of fibrin stabilization. METHODS: We genotyped this polymorphism in 293 consecutive MI patients (62 +/- 12 years; 231 males) from two different European populations. All patients were treated with standard doses of fibrinolytic drugs. Noninvasive assessment of the efficacy of coronary fibrinolysis was evaluated by serial electrocardiograms and creatine kinase time-activity curves. The clinical outcome was also re-evaluated at 24 h (death, reinfarction, or urgent revascularization). RESULTS: Multivariate analysis showed that Leu34 carriers displayed a significantly less efficient fibrinolysis than carriers of Val/Val genotype (p = 0.021; odds ratio [OR] 1.90, 95% confidence interval [CI] 1.10 to 3.28). At 24 h, Leu34 allele carriers had the worst outcome (p = 0.006; OR 2.14, 95% CI 1.25 to 3.68). Interestingly, the combination of the Leu34 allele and nonsmoking status increased the risk of non-reperfusion criteria (p = 0.003, OR 3.77), and worse outcomes at 24 h (p = 0.001, OR 4.55). CONCLUSIONS: In a large cohort of nonselected and consecutive acute MI patients from two different European populations, we show clinical evidence that the presence of the Leu34 allele reduces the efficacy of fibrinolytic therapy.

Aged↗

Effect of urea on self-organization of sodium N-(11-acrylamidoundecanoyl)-L-valinate in water.

In this paper, the hypotheses proposed for the action of urea on the perturbation of molecular assemblies have been tested through studies of the effects of urea on the aggregation properties of a chiral surfactant, sodium N-(11-acrylamidoundecanoyl)-L-valinate in water. Surface tension, fluorescence, and circular dichroism were used to characterize the solution behavior of the amphiphile in the presence of urea. Surface tension measurement indicated decrease of critical aggregation concentration (cac) with the addition of urea in the low concentration range. Fluorescence probe studies using pyrene and 1-anilinonaphthalene indicated solubilization of urea molecules near the aggregate-water interface. Fluorescence anisotropy measurements using 1,6-diphenylhexatriene as probe molecule suggested increase of packing of the hydrocarbon chains of the amphiphiles upon addition of low concentration of urea. Dynamic light scattering measurements showed an increase of the hydrodynamic radius (R(h)) in the presence of increased concentration of urea. At higher concentrations of urea, the R(h) value decreased. Circular dichroism spectra showed the presence of chiral aggregates even in the presence of high concentration of urea.

Acrylamides↗

Synthesis, structure and biological activity of cobalt(II) and copper(II) complexes of valine-derived schiff bases.

We have synthesized two cobalt(II) 2 and copper(II) 3 complexes of valine-derived Schiff bases. The obtained complexes were characterized by elemental analysis, FT-IR and X-ray diffraction. Biological studies of complexes 2 and 3 had been carried out in vitro for antimicrobial activity against Gram-positive, Gram-negative bacteria and human pathogenic fungi. Compound 3 was proven to be a broad spectrum agent, showed a significant inhibition of the growth of Gram-positive bacteria (Staphylococcus aureus, methicillin-resistant S. aureus, Bacillus subtilis, Micrococcus luteus), and pathogenic fungi (Candida spp., Cryptococcus neoformans, Rhodothece glutinis, Saccharomyces cerevisia, Aspergillus spp., Rhizopus nigricans) tested and a moderate activity against Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Proteus vulgaris and Enterobacter aerogenes) tested. The in vitro cytotoxicity of compound 3 was evaluated using hemolytic assay, in which the compound 3 was found to be non-toxic to human erythrocytes even at a concentration of 500mug/mL.

Bacteria↗

Formation of N-(2-hydroxyethyl)valine in human hemoglobin-effect of lifestyle factors.

The formation of N-(2-hydroxyethyl)valine (HEV) in hemoglobin has been considered as a biomarker to assess exogenous and endogenous exposures to ethylene oxide (EO) and/or ethylene (ET). Factors associated with daily exposures to such compounds might significantly affect the formation of HEV. Tobacco smoke containing EO elicited a significant increase in the levels of HEV amongst smokers, although other factors related to lifestyles may warrant further studies. The objective of this study was to specifically analyze HEV using a modified Edman degradation technique in order to study the association between lifestyle related factors (smoking, second-hand smoke exposure, tea and alcohol consumption) and HEV formation in vivo. Total of 148 Taiwanese volunteers with no history of occupational exposure to either EO or ET were recruited in this study. The HEV levels for smokers (204 +/- 151 pmol HEV/g globin, n = 70 ) were greater than those for non-smokers (57 +/- 46 pmol HEV/g globin, n = 78), HEV level increasing with the number of cigarettes smoked by subjects per day with a rate of 8.8 pmol HEV/g globin per cigarettes per day. Further analysis revealed that the rate of HEV formation in our study subjects was significantly associated with the number of daily cigarettes smoked (P < 0.001), but was not associated with tea or alcohol consumption, second-hand smoke exposure, subject age, or subject gender. These results suggest that the significantly higher levels of HEV for smokers than for non-smokers were mainly due to subject exposure to EO contained in cigarette smoke.

Adult↗

Central administration of leucine, but not isoleucine and valine, stimulates feeding behavior in neonatal chicks.

Branched-chain amino acids (BCAAs) are essential amino acids that play a major role in brain energy metabolism. This study was done to elucidate whether central injection of BCAAs influences feeding behavior in chicks. We found that the intracerebroventricular injection of leucine (200 microg) significantly stimulated food intake in neonatal chicks during 30 min postinjection. Additionally, the starting time of feeding and pecking rhythm after injection were significantly accelerated by leucine. In contrast, isoleucine and valine had no effect on ingestive response during experiment periods. Moreover, a metabolite of leucine (alpha-ketoisocaproic acid) at an equimolar concentration of leucine also did not increase food intake in chicks. These results suggest that leucine induces hyperphagia of neonatal chicks and it may be due to the synthesized glutamate by exogenous leucine.

Animals↗

Infrared and Raman spectroscopic studies of l-valine l-valinium perchlorate monohydrate.

FT-IR and FT-Raman spectra were recorded and analyzed for l-valine l-valinium perchlorate monohydrate crystals. The wave number assignments have been made for the functional groups, viz. COOH, COO(-), --[NH(3)](+), C--(CH(3))(2), C--C--N and C--H. One of the two amino acid residues remains in the zwitterionic form while the other residue exists in the cationic form. The symmetry of the ClO(4)(-) anion has been found to be lowered corresponding to ClO(2) group. The hydrogen bonds that prevail between amino acid residues, perchlorate anion and water molecule influence the wave numbers of several stretching and deformation modes to deviate from the expected values.

Hydrogen Bonding↗

Vibrational spectral analysis of DL-valine DL-valinium and DL-methionine DL-methioninium picrates.

A comparative study of infrared and Raman spectra of DL-valine DL-valinium picrate (DL-VVP) and DL-methionine DL-methioninium picrate (DL-MMP) at the room temperature in 4000-50 cm(-1) range helps to determine the effect of hydrogen bonds in these crystals. The existence of the zwitterion and the protonated form in both the crystals has been observed. In DL-MMP, the methionine and the methioninium residues form a dimer through a strong hydrogen bond between them in the crystal. The characteristic bands due to gem-methyl group are observed in the case of DL-VVP. Factor group analysis has been made and the numbers of vibrational modes have been calculated. The tentative assignments of the observed bands are given. The picrate group forms the anion in both the crystals and it is unaffected by the presence of the cations.

Hydrogen Bonding↗

Spectroscopic [correction of eSpectroscopic] and structural properties of valine gramicidin A in monolayers at the air-water interface.

Monomolecular films of valine gramicidin A (VGA) were investigated in situ at the air-water interface by x-ray reflectivity and x-ray grazing incidence diffraction as well as polarization modulation infrared reflection absorption spectroscopy (PM-IRRAS). These techniques were combined to obtain information on the secondary structure and the orientation of VGA and to characterize the shoulder observed in its pi-A isotherm. The thickness of the film was obtained by x-ray reflectivity, and the secondary structure of VGA was monitored using the frequency position of the amide I band. The PM-IRRAS spectra were compared with the simulated ones to identify the conformation adopted by VGA in monolayer. At large molecular area, VGA shows a disordered secondary structure, whereas at smaller molecular areas, VGA adopts an anti-parallel double-strand intertwined beta(5.6) helical conformation with 30 degrees orientation with respect to the normal with a thickness of 25 A. The interface between bulk water and the VGA monolayer was investigated by x-ray reflectivity as well as by comparing the experimental and the simulated PM-IRRAS spectra on D(2)O and H(2)O, which suggested the presence of oriented water molecules between the bulk and the monolayer.

Air↗

Human liver disease decreases methacrylyl-CoA hydratase and beta-hydroxyisobutyryl-CoA hydrolase activities in valine catabolism.

BACKGROUND: Methacrylyl-coenzyme A (MC-CoA) hydratase and beta-hydroxyisobutyryl-coenzyme A (HIB-CoA) hydrolase are key enzymes regulating the toxic concentration of MC-CoA generated in valine catabolism. MATERIALS AND METHODS: We studied the activities and mRNA expression levels of these enzymes in normal human livers and in human livers with chronic hepatitis, cirrhosis, or hepatocellular carcinoma. RESULTS: The activities of both enzymes were significantly lower by 36% to 46% in livers with cirrhosis or hepatocellular carcinoma compared with normals, suggesting a decrease in the capability of detoxifying MC-CoA with these diseases. The mRNA levels for both enzymes measured by quantitative polymerase chain reaction were significantly increased in livers with cirrhosis, but were not altered in those with chronic hepatitis or hepatocellular carcinoma when compared with normal livers. CONCLUSION: Our results suggest that low levels of these enzyme activities in livers with cirrhosis or hepatocellular carcinoma are the result of posttranscriptional regulation in the damaged liver.

Aged↗

Interaction between asymmetric solutes and solvents. Diamides derived from L-valine as stationary phases in gas-liquid partition chromatography.

The resolution of enantiomers of (+/-)-a-amino acid derivatives on optically active diamides derived from L-valine, R1CONHCH[CH(CH3)2]CONHR2, as gas chromatographic stationary phases was studied. The effects of the structure of R1 and R2 in the stationary phases, the structure of the racemic a-amino acid derivatives, temperature, etc., on the separation factors are reported. In the light of these and related results, a more probable mechanism of resolution is presented.

Amides↗

Reduced expression of the isoleucine and valine enzymes in integration host factor mutants of Escherichia coli.

The level of the isoleucine and valine (Ilv) enzymes specified by the ilvB and ilvGEDA operons is reduced in integration host factor mutants (himA and himD) of Escherichia coli K-12. Growth inhibition of these strains in minimal medium can be explained by the decreased amounts of one of the Ilv enzymes, acetohydroxy acid synthase I (AHASI). No growth inhibition, or reduction in AHASI activity, was found in a himA derivative of a mutant strain containing high constitutive levels of AHASI. A strong correlation was observed in himA strains between the reduced amount of the Ilv enzymes and of Ilv-specific messenger RNA. These data suggest that integration host factor may be a positive effector for transcription of the ilvB and ilvGEDA operons.

Acetolactate Synthase↗

X-linked retinitis pigmentosa in two families with a missense mutation in the RPGR gene and putative change of glycine to valine at codon 60.

OBJECTIVE: This study describes the ophthalmic findings in two unrelated white families with X-linked retinitis pigmentosa (XLRP) caused by a missense mutation in the retinitis pigmentosa GTPase regulator (RPGR) gene. DESIGN: Genetic screening and clinical correlation. PARTICIPANTS: Thirty-six families with XLRP seen by the authors were screened for a possible mutation in the RPGR gene to identify three affected hemizygotes with retinitis pigmentosa and four heterozygote carriers in one family and one hemizygote and one carrier in a second family. INTERVENTION: All nine patients underwent a routine ocular examination, including slit-lamp biomicroscopy and a dilated fundus examination. Goldmann visual field kinetic perimetry, static threshold perimetry, and electroretinography also were obtained. The DNA screening was performed on the three affected male patients and four obligate carriers examined from one family and the two examined patients, plus an additional male and obligate carrier, from the second family to determine the presence of any causative mutation in the RPGR gene. MAIN OUTCOME MEASURES: Findings on fundus examination, static threshold and kinetic perimetry, and electroretinography testing were the main outcome measures. RESULTS: A G-->T nucleotide change at position 238 in exon 3 of the RPGR gene resulting in a putative substitute of Gly-->Val at codon 60 was shown to segregate with RP in affected males and the carrier state in female heterozygotes in these two families. The ophthalmologic findings in hemizygotes as well as the carriers in this family were within the spectrum of findings characteristically noted in XLRP families. A tapetal-like reflex was not observed in any of the five female carriers. Psychophysical and electrophysiologic testing on the carriers indicated that cone and rod functions were impaired equivalently. When present in the carriers, visual field restriction was most apparent in, or limited to, the superotemporal quadrant, which corresponded to the retinal pigmentary changes that tended to occur in the inferonasal retina. CONCLUSIONS: A mutation in exon 3 of the RPGR gene, which would result in a putative glycine to valine substitution at codon 60, is associated with a severe clinical phenotype in male patients and a patchy retinopathy without a tapetal-like reflex in carrier females. In these families, heterozygote carriers showed equivalent impairment of their cone and rod function.

Adolescent↗

Spectroscopy, cytotoxicity and DNA-binding of the lanthanum(III) complex of an L-valine derivative of 1,10-phenanthroline.

The interaction of the lanthanum(III) La(III)-L (L=N,N'-bis-(1-carboxy-2-methylpropyl)-1,10-phenanthroline-2,9-dimethanamine) complex with calf thymus DNA was studied by electronic spectra, fluorescence spectra and circular dichroic spectra. The La(III)-L complex was assayed for antitumor activity in vitro against the HL-60 (the human leucocytoma) cells, HCT-8 (the human coloadenocarcinoma) cells, BGC-823 (the human carcinoma of stomach) cells, Bel-7402 (the human liver carcinoma) cells and KB (the human nasopharyngeal carcinoma) cells. The results show that the La(III)-L complex has activity against HL-60 cells, Bel-7402 cells and KB cells. Moreover, it is slightly more effective against Bel-7402 cell line than cisplatin. Using ethidium bromide as a fluorescence probe, the binding mode of the La(III)-L complex to calf-thymus DNA was studied spectroscopically. For comparison, the same measurements were carried out with La(III)-Phen [La(III)-1,10-phenanthroline complex] and La(III)-Val [La(III)-L-valine complex]. The results indicate that the La(III)-L and La(III)-Phen complexes possibly interact with calf-thymus DNA by both intercalative and coordination binding, whereas the La(III)-Val complex interacts with calf-thymus DNA by coordination binding. Kinetics of binding of the three complexes to DNA is for the first time studied using ethidium bromide as a fluorescence probe with stopped-flow spectrophotometer under pseudo-first-order condition. The strong two-step mechanisms in the process of the La(III)-L and La(III)-Phen complexes and one step in the process of the complex La(III)-Val interacting with DNA are observed, and the k(obs) (observed pseudo-first-order rate constant) and E(a) (observed energy of activation) values of binding to DNA are obtained.

Cell Death↗

Gerstmann-Sträussler-Scheinker disease with the PRNP P102L mutation and valine at codon 129.

The most common mutation causing Gerstmann-Sträussler-Scheinker (GSS) disease is P102L in the prion protein. Previously, this mutation has only been found in coupling with methionine at residue 129. We describe a patient with GSS disease in whom the P102L mutation is in coupling with valine at residue 129. The clinical presentation in P102L-V129 differs greatly from that seen in P102-M129 patients.

Adult↗

Improved gas chromatographic-mass spectrometric determination of the N-methylcarbamoyl adduct at the N-terminal valine of globin, a metabolic product of the solvent N,N-dimethylformamide.

A sensitive method for determination of the N-methylcarbamoyl adduct at the N-terminal valine of globin, a new metabolic product of the industrial solvent N,N-dimethylformamide (DMF), has been developed and validated. The method includes conversion of the adduct by the Edman degradation to 3-methyl-5-isopropylhydantoin (MVH), which is followed by optimized gas chromatographic analysis with mass spectrometric detection at m/z 114. The recovery of MVH from terminal N-methylcarbamoylvaline was determined using a model dipeptide to be 90%. Calibration of the method is done with MVH, employing 3-methyl-5-isobutylhydantoin as the internal standard. The limit of detection is 0.2 nmol MVH/g globin when a 100-mg sample is used. Within- and between-day precision is 4-10%. The method has been used to determine the background levels of MVH in unexposed subjects. Further, toxicokinetic studies in volunteers laid the grounds for setting the reference value for biological monitoring of occupational exposure to DMF.

Calibration↗

Ring test for the determination of N-terminal valine adducts of styrene 7,8-oxide with haemoglobin by the modified Edman degradation technique.

A ring-test was organised between three laboratories using different versions of the modified Edman degradation technique for the gas chromatographic-mass spectrometric determination of N-terminal valine adducts of styrene 7,8-oxide. The analyses were performed on a sample of human haemoglobin reacted in vitro with styrene 7,8-oxide and on a set of five haemoglobin samples from mice dosed by i.p. injection of styrene. Strong correlations between the haemoglobin adduct determinations of the different laboratories were observed. However, covariance analysis revealed different slopes for the dose-response curves, indicating differences for the calibration of the reference globin or reference peptide.

Alkylation↗

Oxidation of di- and tripeptides of tyrosine and valine mediated by singlet molecular oxygen, phosphate radicals and sulfate radicals.

Kinetics and mechanism of the oxidation of tyrosine (Tyr) and valine (Val) di- and tripeptides (Tyr-Val, Val-Tyr and Val-Tyr-Val) mediated by singlet molecular oxygen [O(2)((1)Delta(g))], phosphate (HPO(4)(*-) and PO(4)(*2-)) and sulfate (SO(4)(*-)) radicals was studied, employing time-resolved O(2)((1)Delta(g)) phosphorescence detection, polarographic determination of dissolved oxygen and flash photolysis. All the substrates were highly photooxidizable through a O(2)((1)Delta(g))-mediated mechanism. Calculated quotients between the overall and reactive rate constants for the quenching of O(2)((1)Delta(g)) by Tyr-derivatives (k(t)/k(r) values, accounting for the efficiency of the effective photooxidation) were 1.3 for Tyr, 1 for Tyr-Val, 2.8 for Val-Tyr and 1.5 for Val-Tyr-Val. The effect of pH on the kinetics of the photooxidative process confirms that the presence of the dissociated phenolate group of Tyr clearly dominates the O(2)((1)Delta(g)) quenching process. Products analysis by LC-MS indicates that the photooxidation of Tyr di- and tripeptides proceeds with the breakage of peptide bonds. The information obtained from the evolution of primary amino groups upon photosensitized irradiation is in concordance with these results. Absolute rate constants for the reactions of phosphate radicals (HPO(4)(*-) and PO(4)(*2-), generated by photolysis of the P(2)O(8)(4-) at different pH) and sulfate radicals (SO(4)(*-), produced by photolysis of the S(2)O(8)(2-)) with Tyr peptides indicate that for all the substrates, the observed tendency in the rate constants is: SO(4)(*-) > or = HPO(4)(*-) > or = PO(4)(*2-). Formation of the phenoxyl radical of tyrosine was detected as an intermediate involved in the oxidation of tyrosine by HPO(4)(*-).

Amines↗