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Alimentary Pharmacology & Therapeutics Apr 2009Upper gastrointestinal (UGI) bleeding in patients with cirrhosis of the liver induces hyperammonaemia and leads to a catabolic cascade that precipitates life-threatening... (Review)
Review
BACKGROUND
Upper gastrointestinal (UGI) bleeding in patients with cirrhosis of the liver induces hyperammonaemia and leads to a catabolic cascade that precipitates life-threatening complications. The haemoglobin molecule is unique because it lacks the essential amino acid isoleucine and contains high amounts of leucine and valine. UGI bleed therefore presents the gut with protein of very low biologic value, which may be the stimulus to induce net catabolism.
AIM
To describe the hyperammonaemic and catabolic consequences of UGI bleeding in cirrhosis.
METHODS
A semi-structured literature search was performed using PubMed and article references.
RESULTS
It has recently been proven that ('simulation of ') a UGI bleed in patients with cirrhosis leads to impaired protein synthesis that can be restored by intravenous infusion of isoleucine. This may have therapeutic implications for the function of rapidly dividing cells and short half-life proteins such as clotting factors. Renal and small bowel ammoniagenesis were shown to be the most prominent causes for the hyperammonaemia that resulted from a UGI bleed. This provides an explanation for the therapeutic failure of the current clinical therapies that are aimed at large bowel-derived ammonia production. Isoleucine infusion did not diminish renal ammoniagenesis.
CONCLUSIONS
New pharmacological therapies to diminish postbleeding hyperammonaemia should target the altered inter-organ ammonia metabolism and promote ammonia excretion and/or increase the excretion of precursors of ammoniagenesis, e.g. l-ornithine-phenylacetate.
Topics: Amino Acids, Branched-Chain; Gastrointestinal Hemorrhage; Humans; Hyperammonemia; Isoleucine; Liver Cirrhosis
PubMed: 19183148
DOI: 10.1111/j.1365-2036.2009.03938.x -
The Journal of Nutrition Jan 2006There is now an expanding body of evidence to recommend, in the case of adult humans, the use of revised indispensable amino acid requirement values; these are... (Review)
Review
There is now an expanding body of evidence to recommend, in the case of adult humans, the use of revised indispensable amino acid requirement values; these are approximately 2 to 3 times higher than the current international recommendations. The earlier methodologies for determining amino acid requirements, based on nitrogen balance, were criticized because of their design and the associated high energy intakes. The 1985 World Health Organization/Food & Agriculture Organization/United Nations University requirement for leucine has been demonstrated to be too low by short- and long-term (24-h) tracer-derived estimates of leucine oxidation and balance. The best values for leucine requirements come from 24-h direct amino acid oxidation (DAAO) and direct amino acid balance (DAAB) studies. Finally, we also collated all available data from studies on fed-state leucine oxidation with an adequate dietary adaptation period to assess the inflection on the leucine oxidation-leucine intake curve. The mean requirements for leucine, valine, and isoleucine are likely to be 40, 17-25, and 19 mg . kg(-1) . d(-1), respectively. This adds up to a total of approximately 84 mg . kg(-1) . d(-1), which is much lower than the lowest estimate of the total BCAA requirement of approximately 110 mg . kg(-1) . d(-1) made by the short-term indicator amino acid oxidation (IAAO) method, which determined the BCAA requirement from the pattern of oxidation of an indicator amino acid (phenylyalanine) at different levels of BCAA intake. An additional estimate of the leucine requirement was also made by a meta-analysis of all available 24-h DAAO/DAAB data from different studies. This resulted in a higher value for the leucine requirement than that obtained by the specific studies that utilized the 24-h DAAO/DAAB approach; however, even adding this value to the total BCAA requirement does not account for the difference in the total BCAA requirement estimates and the summed individual BCAA estimates.
Topics: Adult; Amino Acids, Branched-Chain; Humans; Isoleucine; Leucine; Nutritional Requirements; Oxidation-Reduction; Valine
PubMed: 16365094
DOI: 10.1093/jn/136.1.256S -
PloS One 2017Diabetes is an irreversible condition characterized by elevated blood glucose levels. Currently, there are no predictive biomarkers for this disease and the existing...
Application of Raman spectroscopy in type 2 diabetes screening in blood using leucine and isoleucine amino-acids as biomarkers and in comparative anti-diabetic drugs efficacy studies.
Diabetes is an irreversible condition characterized by elevated blood glucose levels. Currently, there are no predictive biomarkers for this disease and the existing ones such as hemoglobin A1c and fasting blood glucose are used only when diabetes symptoms are noticed. The objective of this work was first to explore the potential of leucine and isoleucine amino acids as diabetes type 2 biomarkers using their Raman spectroscopic signatures. Secondly, we wanted to explore whether Raman spectroscopy can be applied in comparative efficacy studies between commercially available anti-diabetic drug pioglitazone and the locally used anti-diabetic herbal extract Momordica spinosa (Gilg.)Chiov. Sprague Dawley (SD) rat's blood was used and were pipetted onto Raman substrates prepared from conductive silver paste smeared glass slides. Prominent Raman bands associated with glucose (926, 1302, 1125 cm-1), leucine (1106, 1248, 1302, 1395 cm-1) and isolecucine (1108, 1248, 1437 and 1585 cm-1) were observed. The Raman bands centered at 1125 cm-1, 1395 cm-1 and 1437 cm-1 associated respectively to glucose, leucine and isoleucine were chosen as biomarker Raman peaks for diabetes type 2. These Raman bands displayed decreased intensities in blood from diabetic SD rats administered antidiabetic drugs pioglitazone and herbal extract Momordica spinosa (Gilg.)Chiov. The intensity decrease indicated reduced concentration levels of the respective biomarker molecules: glucose (1125 cm-1), leucine (1395 cm-1) and isoleucine (1437 cm-1) in blood. The results displayed the power and potential of Raman spectroscopy in rapid (10 seconds) diabetes and pre-diabetes screening in blood (human or rat's) with not only glucose acting as a biomarker but also leucine and isoleucine amino-acids where intensities of respectively assigned bands act as references. It also showed that using Raman spectroscopic signatures of the chosen biomarkers, the method can be an alternative for performing comparative efficacy studies between known and new anti-diabetic drugs. Reports on use of Raman spectroscopy in type 2 diabetes mellitus screening with Raman bands associated with leucine and isoleucine molecules acting as reference is rare in literature. The use of Raman spectroscopy in pre-diabetes screening of blood for changes in levels of leucine and isoleucine amino acids is particularly interesting as once elevated levels are noticed, necessary interventions to prevent diabetes development can be initiated.
Topics: Animals; Biomarkers; Blood Glucose; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Isoleucine; Leucine; Momordica; Plant Extracts; Rats; Rats, Sprague-Dawley; Spectrum Analysis, Raman
PubMed: 28926628
DOI: 10.1371/journal.pone.0185130 -
Journal of the American Heart... Mar 2024This study aimed to investigate the causal relationships between branched-chain amino acids (BCAAs) and the risks of hypertension via meta-analysis and Mendelian... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This study aimed to investigate the causal relationships between branched-chain amino acids (BCAAs) and the risks of hypertension via meta-analysis and Mendelian randomization analysis.
METHODS AND RESULTS
A meta-analysis of 32 845 subjects was conducted to evaluate the relationships between BCAAs and hypertension. In Mendelian randomization analysis, independent single-nucleotide polymorphisms associated with BCAAs at the genome-wide significance level were selected as the instrumental variables. Meanwhile, the summary-level data for essential hypertension and secondary hypertension end points were obtained from the FinnGen study. As suggested by the meta-analysis results, elevated BCAA levels were associated with a higher risk of hypertension (isoleucine: summary odds ratio, 1.26 [95% CI, 1.08-1.47]; leucine: summary odds ratio, 1.28 [95% CI, 1.07-1.52]; valine: summary odds ratio, 1.32 [95% CI, 1.12-1.57]). Moreover, the inverse variance-weighted method demonstrated that an elevated circulating isoleucine level might be the causal risk factor for essential hypertension but not secondary hypertension (essential hypertension: odds ratio, 1.22 [95% CI, 1.12-1.34]; secondary hypertension: odds ratio, 0.96 [95% CI, 0.54-1.68]).
CONCLUSIONS
The increased levels of 3 BCAAs positively correlated with an increased risk of hypertension. Particularly, elevated isoleucine level is a causal risk factor for essential hypertension. Increased levels of leucine and valine also tend to increase the risk of essential hypertension, but further verification is still warranted.
Topics: Humans; Amino Acids, Branched-Chain; Isoleucine; Leucine; Mendelian Randomization Analysis; Valine; Hypertension; Essential Hypertension; Genome-Wide Association Study
PubMed: 38420789
DOI: 10.1161/JAHA.123.032084 -
Journal of Molecular Biology Sep 2022While being a thoroughly studied model of dynamic allostery in a small protein, the pathway of signal transduction in the PDZ3 domain has not been fully determined....
While being a thoroughly studied model of dynamic allostery in a small protein, the pathway of signal transduction in the PDZ3 domain has not been fully determined. Here, we investigate peptide binding to the PDZ3 domain by conventional and fully data-driven analyses of molecular dynamics simulations. First, we identify isoleucine 37 as a key residue by widely used computational procedures such as cross-correlation and community network analysis. Simulations of the Ile37Ala mutant show disruption of the coordinated movements of spatially close regular elements of secondary structure. Then, we employ a recently developed unsupervised, data-driven procedure to determine an optimized reaction coordinate (slowest-relaxation eigenvector) of peptide binding. We use this reaction coordinate to improve sampling by restarting additional simulations from the transition state region. Significant differences in the distributions of some of the pairwise residue distances in the bound and unbound states emerge from the projection onto the optimized reaction coordinate. The unsupervised analysis shows that allosteric signaling is transduced from the β2 strand, which forms part of the peptide binding site, to the spatially adjacent β3 and β4 strands, and from there to the α3 helix. The domino-like transmission of a (peptide binding) signal along β strands and α helices that are close in three-dimensional space is likely to be a general mechanism of allostery in single-domain proteins.
Topics: Alanine; Allosteric Regulation; Allosteric Site; Isoleucine; Molecular Dynamics Simulation; Peptides; Protein Binding; Protein Structure, Secondary; Signal Transduction
PubMed: 35640719
DOI: 10.1016/j.jmb.2022.167661 -
Journal of Pharmacological Sciences 2012The branched chain amino acids (BCAAs) leucine, isoleucine, and valine are the most abundant of the essential amino acids. BCAAs have recently been recognized as having... (Review)
Review
The branched chain amino acids (BCAAs) leucine, isoleucine, and valine are the most abundant of the essential amino acids. BCAAs have recently been recognized as having functions other than simple nutrition. The importance of BCAAs as nutrient regulators in protein synthesis was recognized over 20 years ago. Leucine is the most potent of the BCAAs in stimulating muscle protein synthesis, while isoleucine and valine are much less effective. The signaling action of leucine in protein synthesis has been well studied, and the mechanisms are currently under investigation. However, the pharmacological effects of isoleucine and valine have not been clarified. It has recently been reported that, among the BCAAs, leucine and isoleucine act as signals in glucose metabolism. We revealed that isoleucine stimulates both glucose uptake in the muscle and whole body glucose oxidation, in addition to depressing gluconeogenesis in the liver, thereby leading to a hypoglycemic effect in rats. Based on these results, we speculate that isoleucine signaling accelerates catabolism of incorporated glucose for energy production and consumption.
Topics: Animals; Gluconeogenesis; Glucose; Humans; Isoleucine; Leucine; Liver; Muscle Proteins; Oxidation-Reduction; Rats; Valine
PubMed: 22293293
DOI: 10.1254/jphs.11r05fm -
Poultry Science Mar 2020The present study evaluated production performance responses to Ile supplementation in laying hens fed low crude protein (LCP), amino acid (AA) balanced diets. A total...
Egg production and quality responses to increasing isoleucine supplementation in Shaver white hens fed a low crude protein corn-soybean meal diet fortified with synthetic amino acids between 20 and 46 weeks of age.
The present study evaluated production performance responses to Ile supplementation in laying hens fed low crude protein (LCP), amino acid (AA) balanced diets. A total of 179 Shaver white pullets were distributed into 30 battery cages (6 birds/cage, n = 6) and observed over the course of 27 wk in a 2-phase (20 to 27 and 28 to 46 wk of age) feeding program. Five isocaloric diets were formulated for standardized ileal digestible (SID) Lys intake of 750 and 710 mg/D in phase 1 and 2, respectively, and included a positive control with standard levels of crude protein (CP) (CON; 18 and 16% CP for phases 1 and 2), and 4 LCP diets (16 and 14% CP for phase 1 and 2, respectively) with graded levels of Ile to satisfy SID Ile:Lys ratios of 70 (Ile70), 80 (Ile80), 90 (Ile90), and 100% (Ile100). Based on analyzed dietary AA, the calculated SID Ile:Lys of LCP diets were 75, 84, 88, 99% and 66, 72, 82, 95% for phase 1 and 2, respectively. Dietary treatments significantly (P < 0.05) affected feed intake, hen-day egg production (HDEP), egg weight (EW), feed conversion ratio, and egg quality (Haugh unit) and composition (yolk to albumen). Lowering dietary CP negatively affected HDEP with a 3.3 and 1.5% reduction in phase 1 and 2, respectively, and this was restored with the addition of Ile (P < 0.001) suggesting that Ile was limiting in the LCP basal diet. Average EW was reduced in Ile100 only; however, the Ile:Lys appeared to influence egg size uniformity, with Ile90 producing a greater proportion of large (56 g ≤ EW > 63 g) eggs, suggesting that Ile may be used to manipulate EW at the expense of HDEP. Overall, the results indicated that CP in laying hen diets can be reduced by 2% units if fortified with synthetic AA (Met, Lys, Thr, Trp) + Ile, with optimal responses observed between 82 and 88% SID Ile:Lys.
Topics: Amino Acids; Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Chickens; Diet, Protein-Restricted; Dietary Proteins; Dietary Supplements; Dose-Response Relationship, Drug; Female; Ileum; Isoleucine; Ovum; Random Allocation; Reproduction
PubMed: 32111315
DOI: 10.1016/j.psj.2019.10.064 -
Toxins Jul 2022It is widely accepted that eutrophication has played an important role in the formation of harmful cyanobacterial blooms in recent decades, which impacts water quality...
It is widely accepted that eutrophication has played an important role in the formation of harmful cyanobacterial blooms in recent decades, which impacts water quality and ecological environment and causes huge economic losses. Algicidal bacteria have a promising application prospect in controlling cyanobacterial blooms in aquaculture water. Here, the process of the algicidal bacterium strain Bl-zj acting on was explored using transcriptome analysis to elucidate the algicidal mechanism. The results of the co-culture of bacterium and alga showed a strong alga-lysing effect of against with an extreme morphology deformation of the algal cells. A total of 2744 differentially expressed genes of were identified, which were mainly involved in the metabolism of amino acid, carbohydrate, and lipid. In the co-cultured group, the expression of genes mainly enriched in valine, leucine and isoleucine degradation, and fatty acid degradation were significantly increased. However, the expression of the genes related to ribosome were mainly inhibited. Transcriptome analysis showed that obtained ATP and energy by the degradation of valine, leucine, isoleucine, and fatty acids, and destroyed algal cells by efflux pump transporters, secretion of hydrolytic enzymes, antibiotics, proteases, and other secondary metabolites, resulting in algal death and achieving the algicidal effect.
Topics: Bacillus; Brevibacillus; Gene Expression Profiling; Harmful Algal Bloom; Isoleucine; Leucine; Metabolic Networks and Pathways; Microcystis; Valine
PubMed: 35878230
DOI: 10.3390/toxins14070492 -
Nutrients Oct 2021Increases in depression are common in some elderly women. Elderly women often show moderate depressive symptoms, while others display minimal depressive symptoms. These...
Deficiency in the Essential Amino Acids l-Isoleucine, l-Leucine and l-Histidine and Clinical Measures as Predictors of Moderate Depression in Elderly Women: A Discriminant Analysis Study.
Increases in depression are common in some elderly women. Elderly women often show moderate depressive symptoms, while others display minimal depressive symptoms. These discrepancies have produced contradictory and inconclusive outcomes, which have not been explained entirely by deficits in neurotransmitter precursors. Deficiency in some amino acids have been implicated in major depression, but its role in non-clinical elderly women is not well known. An analysis of essential amino acids, depression and the use of discriminant analysis can help to clarify the variation in depressive symptoms exhibited by some elderly women. The aim was to investigate the relationship of essential amino acids with affective, cognitive and comorbidity measures in elderly women without major depression nor severe mood disorders or psychosis, specifically thirty-six with moderate depressive symptoms and seventy-one with minimal depressive symptoms. The plasma concentrations of nineteen amino acids, Beck Depression Inventory (BDI) scores, Geriatric Depression Scale (GDS) scores, global cognitive scores and comorbidities were submitted to stepwise discriminant analysis to identify predictor variables. Seven predictors arose as important for belong to the group based on amino acid concentrations, with the moderate depressive symptoms group characterized by higher BDI, GDS and cognitive scores; fewer comorbidities; and lower levels of l-histidine, l-isoleucine and l-leucine. These findings suggest that elderly women classified as having moderate depressive symptoms displayed a deficiency in essential amino acids involved in metabolism, protein synthesis, inflammation and neurotransmission.
Topics: Aged; Amino Acids, Essential; Cross-Sectional Studies; Depression; Discriminant Analysis; Female; Geriatric Assessment; Histidine; Humans; Isoleucine; Leucine; Predictive Value of Tests; Psychiatric Status Rating Scales
PubMed: 34836128
DOI: 10.3390/nu13113875 -
PloS One 2022To ascertain an appropriate level of isoleucine for LSL-LITE layers (23- to 30-week-old), diets containing total isoleucine concentrations (levels) of 0.66 (Control),...
To ascertain an appropriate level of isoleucine for LSL-LITE layers (23- to 30-week-old), diets containing total isoleucine concentrations (levels) of 0.66 (Control), 0.69, 0.72, 0.75, 0.78, 0.81, and 0.84% were fed as 7 treatments (2730 kcal/kg metabolizable energy) x 7 replicates x 10 birds per replicate. Significance for performance, egg quality, serum biochemistry, and ileal digestibility of protein was determined at P ≤ 0.05. Level, week, and level*week (L*W) were significant for production, egg mass, and feed intake. Level and week were significant for FCR. Week was significant for weight gain. Level was significant for egg weight, specific gravity, and shell thickness; week was also significant for these external egg parameters as well as shape index and proportional shell thickness. L*W was significant for all except shape index. For internal egg measurements, level was significant for proportional yolk, proportional albumen, yolk index, and yolk:albumen. Week was significant for internal egg parameters while L*W significantly affected Haugh unit, proportional albumen weight, yolk index, albumen index, and yolk color. Level was significant for globulin and glucose in serum. Isoleucine at 0.72%, 0.81%, and 0.84% produced the lowest FCR, an important standard in the poultry industry. Considering the low FCR of 1.45 and cost for inclusion as a dietary ingredient, 0.72% isoleucine was chosen for further studies with varying quantities of other branched chain amino acids in diets for young laying hens.
Topics: Isoleucine
PubMed: 35061687
DOI: 10.1371/journal.pone.0261159