High Concentrations Of Histidine Research Articles

Effects of Solid-State Fermentation and the Potential Use of Cassava By-products as Fermented Food

By-products such as cassava bagasse and leaves are discarded though they contain high amounts of carbohydrates, proteins, fat and minerals. The application of solid-state fermentation (SSF) to substrates containing these by-products could improve the bioavailability of nutrients while reducing the amounts of anti-nutritive factors such as cyanide. To evaluate the possibility of using by-products from cassava some techniques, such as colorimetric methods, gas chromatography and high performance of liquid chromatography were applied to evaluate the total cyanide, carbohydrate contents, to characterize the fatty acid profiles, and estimate the essential amino acids after the fermentation process. After the SSF process, the cyanide content was significantly decreased. The profile of essential amino acids showed high concentrations of histidine, isoleucine, valine, methionine and phenylalanine. Some important unsaturated fatty acids were found, such as linoleic acid (18:29,12); α-linolenic acid (18:39,12,15); 11-eicosenoic acid (20:1) and 13,16-docosadienoic acid (22:2). The evaluation of the protein quality showed a significant increase in its bioavailability. The results support the conclusion that currently not used agricultural by-products could become sources of food that provide important quantities of essential nutrients.

Nickel hyperaccumulation mechanisms: a review on the current state of knowledge

Hyperaccumulator plants are unusual plants that accumulate particular metals or metalloids, such as nickel, zinc, cadmium and arsenic, in their living tissues to concentrations that are hundreds to thousands of times greater than what is normal for most plants. The hyperaccumulation phenomenon is rare (exhibited by less than 0.2% of all angiosperms), with most of the ~500 hyperaccumulator species known globally for nickel. This review highlights the contemporary understanding of nickel hyperaccumulation processes, which include root uptake and sequestration, xylem loading and transport, leaf compartmentation and phloem translocation processes. Hyperaccumulator plants have evolved highly efficient physiological mechanisms for taking up nickel in their roots followed by rapid translocation and sequestration into the aerial shoots. The uptake of nickel is mainly involved with low affinity transport systems, presumably from the ZIP family. The presence of high concentrations of histidine prevents nickel sequestration in roots. Nickel is efficiently loaded into the xylem, where it mainly presents as Ni2+. The leaf is the main storage organ, which sequestrates nickel in non-active sites, e.g. vacuoles and apoplast. Recent studies show that phloem translocates high levels of nickel, which has a strong impact on nickel accumulation in young growing tissues.

Interaction of macrophage migration inhibitory factor with ceruloplasmin: role of labile copper ions.

Macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine, is a target for pharmacological treatment of sepsis and malignant tumors. Inhibition of tautomerase activity of MIF in reaction with p-hydroxyphenylpyruvate (HPP) was observed in the presence of ceruloplasmin (CP), a copper-containing plasma protein. Binding labile copper ions to CP (CP+Cu(II)) is a prerequisite for MIF inhibiting. CP+Cu(II) is shown to be an uncompetitive inhibitor of MIF (Ki ~ 37 nM), which suggests formation of a complex 'MIF-HPP-CP-Cu(II)'. Filtration of CP+Cu(II) on a column with Chelex-100, otherwise the presence of high concentrations of histidine, cysteine or methionine abrogated the inhibitory effect of CP. Adding salts of Co(II) and Ni(II) that replace copper ions in the labile sites prevented the inhibitory effect of CP+Cu(II). Limited proteolysis of CP by thrombin diminished its oxidase activity in reaction with p-phenylenediamine, but endowed it with the capacity of inhibiting MIF. Covalent modification of MIF by phenylmethylsulfonyl fluoride (PMSF) resulted in binding of MIF-PMSF to CP immobilized on CM5 chip, the dissociation constant being 4.2 μM. In D-galactosamine-sensitized mice CP+Cu(II) increased the LPS-induced lethality from 54 to 100%, while administration of antibodies against MIF prevented the lethal effect. The enhancement by CP+Cu(II) of the pro-inflammatory signal of MIF is discussed.

Administration of Histidine to Female Rats Induces Changes in Oxidative Status in Cortex and Hippocampus of the Offspring

Histidinemia is an inherited metabolic disorder biochemically characterized by high concentrations of histidine in biological fluids. Usually affected patients are asymptomatic although some individuals have mental retardation and speech disorders. Considering the high prevalence of histidinemia and the scarce information on the effects of maternal histidinemia on their progeny, we investigated various parameters of oxidative stress in brain cortex and hippocampus of the offspring from female rats that received histidine (0.5 mg/g of body weight) in the course of pregnancy and lactation. At 21 days of age we found a significant increase of thiobarbituric acid reactive substances (TBARS), 2',7'-dihydrodichlorofluorescein oxidation, superoxide dismutase (SOD) activity, catalase (CAT) activity, total sulfhydryls and glutathione (GSH) content in cerebral cortex and hippocampus. We also verified that at 60 days of age, GSH, SOD and total sulfhydryls returned to normal levels in brain cortex, while the other parameters decreased in the same structure. In the hippocampus, at 60 days of age GSH returned to normal levels, CAT persisted elevated and the other parameters decreased. These results indicate that histidine administration to female rats can induce oxidative stress in the brain from the offspring, which partially recovers 40 days after breastfeeding stopped.

Relating olfactory neurotoxicity to altered olfactory-mediated behaviors in rainbow trout exposed to three currently-used pesticides

Odor-evoked neurophysiological responses can form the basis for behavioral responses. Here we first characterized olfactory-mediated behavioral and neurophysiological responses of juvenile rainbow trout to the amino acid l-histidine, then looked at whether there were similar responses to the carbamate antisapstain IPBC and the herbicides atrazine and Roundup ®, and lastly explored how exposures to these pesticides modified the l-histidine responses. Trout were behaviorally attracted to 10 −7 M l-histidine (as assayed in a counter-current olfactometer), but this preference behavior switched to indifference with higher histidine concentrations. Neurophysiologically, the summed electrical responses of peripheral olfactory neurons, as measured using electro-olfactogram (EOG), was 0.843 ± 0.252 mV to 10 −7 M l-histidine. Of the pesticides, only Roundup ® evoked EOGs, indicating the amino acid-based pesticide may have acted as an odorant, and generated a behavioral response: it was avoided at active ingredient [AI; glyphosate isopropyl amine] concentrations ≥ 10 mg/l. With 30 min pesticide exposures, 10 −7 M l-histidine preference behavior was eliminated following exposure to 1 μg/l IPBC and atrazine, and 100 μg/l AI Roundup ®. Similarly, 10 −7 M l-histidine-evoked EOGs were significantly reduced by exposure to 1 μg/l IPBC, 10 μg/l atrazine, and 100 μg/l AI Roundup ®. When combined together, the results demonstrate that typical preference behavior can be abolished when neurophysiological responses are reduced by >60% of control. This asymmetry in response thresholds suggests that behavioral responses may be more sensitive toxicological endpoints than neurophysiological responses.

Influence of histidine on the stability and physical properties of a fully human antibody in aqueous and solid forms.

The aim of the study was to investigate the effect of histidine on the stability and physical properties of a fully human anti-IL8 monoclonal antibody (ABX-IL8) in aqueous and solid forms. Using a fractional factorial design, we tested many excipients, including histidine, sucrose, and other commonly used excipients, on the stability and physical properties of the antibody in both liquid and lyophilized forms. Antibody stability and physical properties were evaluated using size-exclusion high-performance liquid chromatography (SEC-HPLC), sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and a viscometer. Residual moisture content was determined by coulometric Karl Fischer titrator. Differential scanning calorimetry (DSC) was used to detect the glass transition temperatures (Tg) of the solid cakes and melting temperatures (Tm) of the antibody in liquid formulations. Fourier-transform infrared (FTIR) spectroscopy was used to examine the overall secondary structure. Increasing the histidine concentration in the bulk solution inhibited the increases of high-molecular-weight (HMW) species and aggregates upon lyophilization and storage. In addition, histidine bulk enhanced solution stability of the antibody under freezing and thermal stress conditions, as evidenced by the lower levels of aggregates. Furthermore, histidine reduced viscosity of the antibody solution, which is desirable for the manufacture of the dosage form. However, high concentrations of histidine in liquid formulations led to coloration of the solution and high levels of aggregates on storage at elevated temperature (40 degrees C) after the formulations were exposed to stainless steel containers during bulk freezing-thawing. Histidine enhanced the stability of ABX-IL8 in both aqueous and lyophilized forms. Histidine also improved the physical properties such as reducing the solution viscosity. Liquid formulations containing high concentrations of histidine should not be stored in stainless steel tanks at elevated temperatures.

Neutral amino acid transport in bovine articular chondrocytes.

1. The sodium-dependent amino acid transport systems responsible for proline, glycine and glutamine transport, together with the sodium-independent systems for leucine and tryptophan, have been investigated in isolated bovine chondrocytes by inhibition studies and ion replacement. Each system was characterized kinetically. 2. Transport via system A was identified using the system-specific analogue alpha-methylaminoisobutyric acid (MeAIB) as an inhibitor of proline, glycine and glutamine transport. 3. Uptake of proline, glycine and glutamine via system ASC was identified by inhibition with alanine or serine. 4. System Gly was identified by the inhibition of glycine transport with excess sarcosine (a substrate for system Gly) whilst systems A and ASC were inhibited. This system, having a very limited substrate specificity and tissue distribution, was also shown to be Na+ and Cl- dependent. Evidence for expression of the system Gly component GLYT-1 was obtained using the reverse transcriptase-polymerase chain reaction (RT-PCR). 5. System N, also of narrow substrate specificity and tissue distribution, was shown to be present in chondrocytes. Na+-dependent glutamine uptake was inhibited by high concentrations of histidine (a substrate of system N) in the presence of excess MeAIB and serine. 6. System L was identified using the system specific analogue 2-aminobicyclo(2,2, 1)heptane-2-carboxylic acid (BCH) and D-leucine as inhibitors of leucine and tryptophan transport. 7. The presence of system T was tested by using leucine, tryptophan and tyrosine inhibition. It was concluded that this system was absent in the chondrocyte. 8. Kinetic analysis showed the Na+-independent chondrocyte L system to have apparent affinities for leucine and tryptophan of 125 +/- 27 and 36 +/- 11 microM, respectively. 9. Transport of the essential amino acids leucine and tryptophan into bovine chondrocytes occurs only by the Na+-independent system L, but with a higher affinity than the conventional L system.

Amino Acid-dependent Control of p70s6k: INVOLVEMENT OF tRNA AMINOACYLATION IN THE REGULATION

In human T-lymphoblastoid cells, downstream signaling events of mammalian target of rapamycin (mTOR), including the activity of p70(s6k) and phosphorylation of eukaryotic initiation factor 4E-binding protein 1, were dependent on amino acid concentration in the culture media, whereas other growth-related protein kinases were not. Amino acid-induced p70(s6k) activation was completely inhibited by rapamycin but only partially inhibited by wortmannin. Moreover, amino acid concentration similarly affected the p70(s6k) activity, which was dependent on a rapamycin-resistant mutant (S2035I) of mTOR. These data indicate that mTOR is required for amino acid-dependent activation of p70(s6k). The mechanism by which amino acids regulate p70(s6k) activity was further explored: 1) amino acid alcohols, which inhibit aminoacylation of tRNA by their competitive binding to tRNA synthetases, suppressed p70(s6k) activity; 2) suppression of p70(s6k) by amino acid depletion was blocked by cycloheximide or puromycin, which inhibit utilization of aminoacylated tRNA in cells; and 3) in cells having a temperature-sensitive mutant of histidyl tRNA synthetase, p70(s6k) was suppressed by a transition of cells to a nonpermissible temperature, which was partially restored by addition of high concentrations of histidine. These results indicate that suppression of tRNA aminoacylation is able to inhibit p70(s6k) activity. Deacylated tRNA may be a factor negatively regulating p70(s6k).

Mechanisms of myocardial protection by amino acids: facts and hypotheses.

1. Positive inotropic effect of taurine and improvement of cardiac performance of failing heart are mediated through the modulation of Ca2+ movement through the sarcolemma. 2. Cardioprotection with glutamate and aspartate is related to enhanced anaerobic energy formation in mitochondria coupled with succinate formation and, probably, with the relieving of glycolytic flux. During reperfusion, both amino acids replenish the malate-aspartate shuttle reactants, thereby facilitating glucose oxidation. 3. Increased intracellular concentrations of branched chain amino acids (leucine, valine and isoleusine) stimulate formation of acetyl-coenzyme (CoA) and succinyl-CoA and, thus, recovery of oxidative metabolism. 4. Methionine and cysteine enhance force of contraction by N-methylation of membrane phospholipids of the sarcolemma and sarcoplasmic reticulum. Methionine and, to a lesser extent, cysteine may reduce myocardial damage by oxygen radical species. 5. Histidine exerts antioxidant properties as a scavenger of singlet oxygen and OH radicals. High concentrations of histidine provide intracellular buffering to stimulate anaerobic energy formation.

Comparative responses of genetically lean and fat chickens to lysine, arginine and non‐essential amino acid supply. II. plasma amino acid responses

1. Three experiments performed to study the effects of amino acid imbalances on the growth of genetically lean (LL) and fat (FL) male chickens from 28 to 42 d of age were described by Leclercq et al. (1994). The plasma amino acid concentrations of birds on selected treatments from that paper are reported here. In experiment 1, three dietary concentrations of digestible lysine were compared (4.75, 6.75 and 7.75 g/kg). In experiment 2, two dietary concentrations of digestible arginine were compared (6.53 and 10.00 g/kg). In experiment 3, three diets were compared: a high-protein diet (189 g CP/kg), a low-protein diet containing added essential amino acids (144 g CP/kg), and this low-protein diet supplemented with 40 g/kg of non-essential amino acids (NEAA; glutamic and aspartic acids). 2. The present results are compared with two earlier reports on the same genotypes. The LL consistently had lower plasma concentrations of methionine, cystine, phenylalanine, isoleucine and valine, and higher concentrations of histidine, than the FL chickens. In 4 of 5 experiments, LL leucine concentrations were lower, and glutamic acid, tyrosine, glutamine and alanine were higher, than in the FL. The other amino acids measured; arginine, lysine, aspartic acid, glycine and serine, exhibited variable responses among the experiments. 3. When the limiting essential amino acids, lysine and arginine, were added to a deficient diet, the plasma concentration of the supplemented amino acid increased while the others remained constant or decreased. 4. When glutamic and aspartic acids were added to the low protein diet, plasma amino acid responses were similar to those of adding a limiting amino acid to a deficient diet, except that alanine exhibited a dramatic increase. 5. Although there were genotype by diet interactions for several amino acids, the interactions were caused by differences in the degree of the responses, not in their direction. 6. These results suggest that the FL and LL genotypes do not utilise various amino acids with the same efficiency and, as a consequence, the ideal profile of dietary amino acids should not be the same for both lines. The results support the hypothesis that selection for fatness and leanness changed the amino acid requirements independently of the effects of food intake.

Free imidazole compounds in white and dark muscles of migratory marine fish

1. 1. Extractive nitrogenous components were analyzed in specimens of white and dark muscles of three tunas and the Pacific saury. 2. 2. Tunas contained high concentrations of histidine, anserine and creatine in white muscle, and of taurine, anserine and creatine in dark muscle. 3. 3. Imidazole compounds were determined in both muscles of 11 migratory marine fish. Histidine was found in great quantities in all species except swordfish, anserine was found in relatively large amounts in tunas and swordfish, but carnosine was only present in small amounts in yellowfin and skipjack tunas. 4. 4. The dark muscle had a lower content of imidazole compounds than white muscle.

Evaluation of the mutagenic potential of corn (Zea mays L.) grown in untreated and atrazine (AAtrex) treated soil in the field.

Bacterial assays using extracts from field corn plants (harvested at one month, silage and mature stages) do not indicate that soil treatment with atrazine, at its maximum use rate, alters the endogenous mutagens present in these extracts, nor that atrazine itself is degraded to mutagenic products. Extracts of corn grown in soil treated with AAtrex were equally mutagenic with those of corn grown in untreated soil when tested in Salmonella typhimurium TA-100 by a reversion assay or in Salmonella typhimurium TM-677 in a forward mutation assay. Higher concentrations of histidine in corn grown in AAtrex treated soil may interfere with the reversion assay, but do not affect the forward mutation assay. The nature of the agent(s) responsible for the positive response was not determined. The mutagenicity may be due to natural plant constituents, an artifact of the sample preparation, or mycotoxins from some unrecognized plant infection. The experimental results in these field studies do not show that atrazine is degraded or metabolized by corn plants to mutagens in this sensitive bacterial assay.

Maternal histidine metabolism and its effect on foetal development in the mouse.

THERE have been reports1,2 of possible deleterious effects on the mental development of children due to maternal histidinaemia, in which a deficiency of the enzyme histidase leads to the exposure of the foetus to abnormally high concentrations of histidine and its imidazole derivatives. This is analagous to the well established case of maternal phenylketonuria3 which can lead to mental retardation in metabolically normal children. There is also a suggested link4 between low maternal concentrations of two enzymes in galactose metabolism and infantile cataracts. We report here work on the nature of the maternal effects of histidinaemia using mutant mice which are the homologues of the human condition5–7.