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Physiological Research Jul 2021The article shows that skeletal muscle plays a dominant role in the catabolism of branched-chain amino acids (BCAAs; valine, leucine, and isoleucine) and the... (Review)
Review
The role of skeletal muscle in the pathogenesis of altered concentrations of branched-chain amino acids (valine, leucine, and isoleucine) in liver cirrhosis, diabetes, and other diseases.
The article shows that skeletal muscle plays a dominant role in the catabolism of branched-chain amino acids (BCAAs; valine, leucine, and isoleucine) and the pathogenesis of their decreased concentrations in liver cirrhosis, increased concentrations in diabetes, and nonspecific alterations in disorders with signs of systemic inflammatory response syndrome (SIRS), such as burn injury and sepsis. The main role of skeletal muscle in BCAA catabolism is due to its mass and high activity of BCAA aminotransferase, which is absent in the liver. Decreased BCAA levels in liver cirrhosis are due to increased use of the BCAA as a donor of amino group to alpha-ketoglutarate for synthesis of glutamate, which in muscles acts as a substrate for ammonia detoxification to glutamine. Increased BCAA levels in diabetes are due to alterations in glycolysis, citric acid cycle, and fatty acid oxidation. Decreased glycolysis and citric cycle activity impair BCAA transamination to branched-chain keto acids (BCKAs) due to decreased supply of amino group acceptors (alpha-ketoglutarate, pyruvate, and oxaloacetate); increased fatty acid oxidation inhibits flux of BCKA through BCKA dehydrogenase due to increased supply of NADH and acyl-CoAs. Alterations in BCAA levels in disorders with SIRS are inconsistent due to contradictory effects of SIRS on muscles. Specifically, increased proteolysis and insulin resistance tend to increase BCAA levels, whereas activation of BCKA dehydrogenase and glutamine synthesis tend to decrease BCAA levels. The studies are needed to elucidate the role of alterations in BCAA metabolism and the effects of BCAA supplementation on the outcomes of specific diseases.
Topics: Amino Acids, Branched-Chain; Animals; Diabetes Mellitus; Humans; Isoleucine; Leucine; Liver Cirrhosis; Metabolic Diseases; Muscle, Skeletal; Valine
PubMed: 33982576
DOI: 10.33549/physiolres.934648 -
International Journal of Molecular... Nov 2020The molecular design of short peptides to achieve a tailor-made functional architecture has attracted attention during the past decade but remains challenging as a...
The molecular design of short peptides to achieve a tailor-made functional architecture has attracted attention during the past decade but remains challenging as a result of insufficient understanding of the relationship between peptide sequence and assembled supramolecular structures. We report a hybrid-resolution model to computationally explore the sequence-structure relationship of self-assembly for tripeptides containing only phenylalanine and isoleucine. We found that all these tripeptides have a tendency to assemble into nanofibers composed of laterally associated filaments. Molecular arrangements within the assemblies are diverse and vary depending on the sequences. This structural diversity originates from (1) distinct conformations of peptide building blocks that lead to different surface geometries of the filaments and (2) unique sidechain arrangements at the filament interfaces for each sequence. Many conformations are available for tripeptides in solution, but only an extended β-strand and another resembling a right-handed turn are observed in assemblies. It was found that the sequence dependence of these conformations and the packing of resulting filaments are determined by multiple competing noncovalent forces, with hydrophobic interactions involving Phe being particularly important. The sequence pattern for each type of assembly conformation and packing has been identified. These results highlight the importance of the interplay between conformation, molecular packing, and sequences for determining detailed nanostructures of peptides and provide a detailed insight to support a more precise design of peptide-based nanomaterials.
Topics: Amino Acid Sequence; Drug Design; Hydrophobic and Hydrophilic Interactions; Isoleucine; Microscopy, Electron, Scanning; Molecular Dynamics Simulation; Nanofibers; Nanotechnology; Oligopeptides; Phenylalanine; Protein Conformation; Protein Engineering; Protein Multimerization
PubMed: 33182629
DOI: 10.3390/ijms21228431 -
Molecules (Basel, Switzerland) Nov 2016Obesity and insulin resistance (IR) are interdependent multifactorial processes that cannot be understood separately. Obesity leads to systemic inflammation and... (Review)
Review
Obesity and insulin resistance (IR) are interdependent multifactorial processes that cannot be understood separately. Obesity leads to systemic inflammation and increased levels of free fatty acids that provoke IR and lipotoxicity. At the same time, IR exacerbates adipose cell dysfunction, resulting in chronic inflammation and major lipotoxic effects on nonadipose tissues. 4-Hydroxyisoleucine (4-OHIle), a peculiar nonprotein amino acid isolated from fenugreek () seeds, exhibits interesting effects on IR related to obesity. 4-OHIle increases glucose-induced insulin release, and the insulin response mediated by 4-OHIle depends on glucose concentration. The beneficial effects observed are related to the regulation of blood glucose, plasma triglycerides, total cholesterol, free fatty acid levels, and the improvement of liver function. The mechanism of action is related to increased Akt phosphorylation and reduced activation of Jun N-terminal kinase (JNK)1/2, extracellular signal-regulated kinase (ERK)1/2, p38 mitogen-activated protein kinase (MAPK), and nuclear factor (NF)-κB. Here, we present a review of the research regarding the insulinotropic and insulin-sensitising activity of 4-OHIle in in vitro and in vivo models.
Topics: Animals; Glucose; Humans; In Vitro Techniques; Insulin Resistance; Isoleucine; Liver; Liver Function Tests; MAP Kinase Signaling System; Obesity; Plant Extracts; Trigonella
PubMed: 27879673
DOI: 10.3390/molecules21111596 -
International Journal of Molecular... Mar 2022Valine (Val) alone or in combination with isoleucine (Ile) improves the growth under severe protein restriction; however, the underlying mechanisms remain unknown. In...
A Mixture of Valine and Isoleucine Restores the Growth of Protein-Restricted Pigs Likely through Improved Gut Development, Hepatic IGF-1 Pathway, and Plasma Metabolomic Profile.
Valine (Val) alone or in combination with isoleucine (Ile) improves the growth under severe protein restriction; however, the underlying mechanisms remain unknown. In this study, we assessed whether Val/Ile-induced growth in protein-restricted pigs is associated with changes in gut development, hepatic insulin-like growth factor 1 (IGF-1) production, and blood metabolomics. Forty piglets were assigned to five dietary groups: positive control (PC) with standard protein content; low protein (LP) with very low protein content; and LP supplemented with Val (LPV), Ile (LPI), and Val and Ile (LPVI). LPVI reversed the negative effects of VLP diets on growth and gut morphology. Both LPV and LPVI restored the reduced transcript of IGF-1 while decreasing the transcript of insulin-like growth factor binding protein 1 (IGFBP1) in the liver. LPV and LPVI recovered the reduced plasma Val, glycine, and leucine concentrations, which were positively correlated with improved gut morphology and the hepatic IGF-1 gene expression and negatively correlated with hepatic IGFBP1 mRNA abundance. In conclusion, supplementation with a combination of Val and Ile into the VLP diets restored the decreased growth performance of pigs fed with these diets likely through improved gut development, hepatic IGF-1 expression and bioavailability, and plasma metabolomics profile.
Topics: Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Diet; Diet, Protein-Restricted; Insulin-Like Growth Factor I; Isoleucine; Liver; Metabolomics; Swine; Valine
PubMed: 35328720
DOI: 10.3390/ijms23063300 -
Phytochemistry Sep 2009Plant tissues are highly vulnerable to injury by herbivores, pathogens, mechanical stress, and other environmental insults. Optimal plant fitness in the face of these... (Review)
Review
Plant tissues are highly vulnerable to injury by herbivores, pathogens, mechanical stress, and other environmental insults. Optimal plant fitness in the face of these threats relies on complex signal transduction networks that link damage-associated signals to appropriate changes in metabolism, growth, and development. Many of these wound-induced adaptive responses are triggered by de novo synthesis of the plant hormone jasmonate (JA). Recent studies provide evidence that JA mediates systemic wound responses through distinct cell autonomous and non-autonomous pathways. In both pathways, bioactive JAs are recognized by an F-box protein-based receptor system that couples hormone binding to ubiquitin-dependent degradation of transcriptional repressor proteins. These results provide a framework for understanding how plants recognize and respond to tissue injury.
Topics: Arabidopsis Proteins; Cyclopentanes; Gene Expression Regulation, Plant; Isoleucine; Models, Biological; Molecular Structure; Oxylipins; Signal Transduction
PubMed: 19695649
DOI: 10.1016/j.phytochem.2009.07.018 -
Nutrients Aug 2020Chronic isoleucine supplementation prevents diet-induced weight gain in rodents. Acute-isoleucine administration improves glucose tolerance in rodents and reduces...
Chronic isoleucine supplementation prevents diet-induced weight gain in rodents. Acute-isoleucine administration improves glucose tolerance in rodents and reduces postprandial glucose levels in humans. However, the effect of chronic-isoleucine supplementation on body weight and glucose tolerance in obesity is unknown. This study aimed to investigate the impact of chronic isoleucine on body weight gain and glucose tolerance in lean and high-fat-diet (HFD) induced-obese mice. Male C57BL/6-mice, fed a standard-laboratory-diet (SLD) or HFD for 12 weeks, were randomly allocated to: (1) Control: Drinking water; (2) Acute: Drinking water with a gavage of isoleucine (300 mg/kg) prior to the oral-glucose-tolerance-test (OGTT) or gastric-emptying-breath-test (GEBT); (3) Chronic: Drinking water with 1.5% isoleucine, for a further six weeks. At 16 weeks, an OGTT and GEBT was performed and at 17 weeks metabolic monitoring. In SLD- and HFD-mice, there was no difference in body weight, fat mass, and plasma lipid profiles between isoleucine treatment groups. Acute-isoleucine did not improve glucose tolerance in SLD- or HFD-mice. Chronic-isoleucine impaired glucose tolerance in SLD-mice. There was no difference in gastric emptying between any groups. Chronic-isoleucine did not alter energy intake, energy expenditure, or respiratory quotient in SLD- or HFD-mice. In conclusion, chronic isoleucine supplementation may not be an effective treatment for obesity or glucose intolerance.
Topics: Animals; Blood Glucose; Diet, High-Fat; Dietary Supplements; Glucose Intolerance; Glucose Tolerance Test; Humans; Hyperglycemia; Isoleucine; Male; Mice, Inbred C57BL; Negative Results; Nutritional Physiological Phenomena; Obesity; Thinness; Weight Gain
PubMed: 32823899
DOI: 10.3390/nu12082446 -
Genes Jun 2022This study sought to provide a theoretical basis for effectively controlling the content of higher alcohols and esters in fermented foods. In this work, isoleucine (Ile)...
This study sought to provide a theoretical basis for effectively controlling the content of higher alcohols and esters in fermented foods. In this work, isoleucine (Ile) or leucine (Leu) at high levels was used as the sole nitrogen source for a mutant and its parental 38 to investigate the effects of the addition of amounts of Ile or Leu and on the aroma components in the flavor profile using gas chromatography mass spectrometer (GC-MS). The results showed that 2-methyl-butyraldehyde, 2-methyl-1-butanol, and 2-methylbutyl-acetate were the products positively correlated with the Ile addition amount. In addition, 3-methyl-butyraldehyde, 3-methyl-1-butanol, and 3-methylbutyl-acetate were the products positively correlated with Leu addition amount. deletion resulted in a significant decline in the yields of 2-methyl-butyraldehyde, 3-methyl-butyraldehyde,2-methyl-1-butanol, and 3-methyl-1-butanol, but also an increase in the yields of 2-methylbutyl-acetate and 3-methylbutyl-acetate. We speculated that regulated the front and end of this metabolite chain in a feedback manner. Improved metabolic chain analyses, including the simulated energy metabolism of Ile or Leu, indicated that reducing the added amount of branched-chain amino acids, mutation, and eliminating the role of energy cofactors such as NADH/NAD+ were three important ways to control the content of high alcohols and esters in fermented foods.
Topics: 1-Butanol; Acetates; Alcohols; Esters; Isoleucine; Leucine; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Transaminases
PubMed: 35885961
DOI: 10.3390/genes13071178 -
Poultry Science Apr 2016Poultry maintenance requirements for valine, isoleucine, and tryptophan were measured by nitrogen balance using different unit systems. The nitrogen balance trial lasted...
Poultry maintenance requirements for valine, isoleucine, and tryptophan were measured by nitrogen balance using different unit systems. The nitrogen balance trial lasted 5 d with 48 h of fasting (with roosters receiving only water+sucrose) and the last 72 h for feeding and excreta collection. Forty grams of each diet first-limiting in valine, isoleucine, or tryptophan was fed by tube each day (3 d) to give a range of intakes from 0 to 101, 0 to 119, and 0 to 34 mg/kg BW d of valine, isoleucine, and tryptophan, respectively. A nitrogen-free diet containing energy, vitamins, and minerals, meeting the rooster requirements, was offered ad libitum during these three d. To confirm that the amino acids studied were limiting, a treatment was added with a control diet formulated by adding 0.24 g/kg of L-valine, 0.21 g/kg of L-isoleucine, and 0.10 g/kg of L-tryptophan to the diets with lower amino acid level. Excreta were collected during the last 3 d of the balance period and the nitrogen content of the excreta was analyzed. For each amino acid, a linear regression between nitrogen retention (NR) and amino acid intake was performed. The equations from linear regression were: NR=-98.6 (±10.1)+2.4 (±0.2)×Val, NR=-46.9 (±7.1)+2.3 (±0.1)×Ile, NR=-39.5 (±7.7)+7.3 (±0.4)×Trp; where Val, Ile, and Trp are the intakes of valine, isoleucine, and tryptophan in mg/kg body weight per d, respectively. The valine, isoleucine, and tryptophan required to maintain the body at zero NR were calculated to be 41, 20, and 5 mg/kg body weight per d, respectively. For the system unit mg per kg of metabolic weight, the intake of valine, isoleucine, and tryptophan was 59, 32, and 9, respectively. Considering the degree of maturity of the animal and body protein content (BPm (0.73)×u), the amounts of valine, isoleucine, and tryptophan required for maintenance were calculated to be 247, 134, and 37 mg per unit of maintenance protein (BPm (0.73)×u) per d. Maintenance requirement is more adequately expressed as body protein content.
Topics: Animal Feed; Animal Husbandry; Animal Nutritional Physiological Phenomena; Animals; Chickens; Diet; Digestion; Isoleucine; Male; Tryptophan; Valine
PubMed: 26769273
DOI: 10.3382/ps/pev380 -
Poultry Science Dec 2022A study was conducted to understand the relationship among dietary branched-chain amino acids (BCAA) on the performance of Ross 344 × 708 male broilers. A total of...
A study was conducted to understand the relationship among dietary branched-chain amino acids (BCAA) on the performance of Ross 344 × 708 male broilers. A total of 2,592 d-old male chicks were randomly placed into 144-floor pens according to a 2 full factorial central composite design (CCD) with 20 treatments (14 treatments and 6 center points). Each treatment consisted of varying digestible Ile:Lys (52 to 75), Val:Lys (64 to 87), and Leu:Lys (110 to 185) ratios. Birds and feed were weighed at 20 and 34 d of age to determine body weight gain (BWG), feed intake, and feed conversion ratio (FCR). At 35 d of age, feather amino acid composition and carcass characteristics were evaluated. Data were analyzed as CCD using the surface response option of JMP v. 15. Body weight gain (1,332 g; P < 0.001; R = 0.93) and FCR (1.54; P = 0.002; R = 0.88) were optimized at the lowest Leu:Lys ratio (110) with moderate Val:Lys (78 to 79) and Ile:Lys (65 to 66) ratios. Poorer BWG and FCR were observed as Leu:Lys ratio increased while increasing Val:Lys and Ile:Lys ratios alleviated the poor performance. Carcass (71.5%; P = 0.031; R = 0.76) and breast yield (26.7%; P < 0.001; R = 0.96) were maximized at the highest Leu:Lys ratio. This effect was complemented by increasing Ile:Lys ratio beyond 68. Lower Ile:Lys and Val:Lys ratios were required to maximize carcass and breast yield at the lowest Leu:Lys ratio. However, this strategy yielded less meat than providing a high Leu:Lys ratio diet. Dietary BCAA had little effect on altering the composition of feather protein and amino acid (P > 0.10). These results suggest that optimum BCAA ratios to Lys may vary depending on response criteria and demonstrate the importance of maintaining proper Val and Ile ratios centered on dietary Leu. Live performance can be optimized in diets with low Leu:Lys ratios; however, meat yield can be enhanced by increasing dietary Leu:Lys along with Ile:Lys ratios.
Topics: Animals; Male; Isoleucine; Leucine; Valine; Chickens; Animal Feed; Diet; Amino Acids, Branched-Chain; Weight Gain; Amino Acids
PubMed: 36191517
DOI: 10.1016/j.psj.2022.102140 -
The Journal of Nutrition Mar 2012Understanding the regulatory effects of individual amino acids (AA) on milk protein synthesis rates is important for improving protein and AA requirement models for...
Understanding the regulatory effects of individual amino acids (AA) on milk protein synthesis rates is important for improving protein and AA requirement models for lactation. The objective of this study was to examine the effects of individual essential AA (EAA) on cellular signaling and fractional protein synthesis rates (FSR) in bovine mammary cells. Omission of L-arginine, L-isoleucine, L-leucine, or all EAA reduced (P < 0.05) mammalian target of rapamycin (mTOR; Ser2448) and ribosomal protein S6 (rpS6; Ser235/236) phosphorylation in MAC-T cells. Phosphorylation of mTOR and rpS6 kinase 1 (S6K1; Thr389) decreased (P < 0.05) in the absence of L-isoleucine, L-leucine, or all EAA in lactogenic mammary tissue slices. Omission of L-tryptophan also reduced S6K1 phosphorylation (P = 0.01). Supplementation of L-leucine to media depleted of EAA increased mTOR and rpS6 and decreased eukaryotic elongation factor 2 (Thr56) phosphorylation (P < 0.05) in MAC-T cells. Supplementation of L-isoleucine increased mTOR, S6K1, and rpS6 phosphorylation (P < 0.05). No single EAA considerably affected eukaryotic initiation factor 2-α (eIF2α; Ser51) phosphorylation, but phosphorylation was reduced in response to provision of all EAA (P < 0.04). FSR declined when L-isoleucine (P = 0.01), L-leucine (P = 0.01), L-methionine (P = 0.02), or L-threonine (P = 0.07) was depleted in media and was positively correlated (R = 0.64, P < 0.01) with phosphorylation of mTOR and negatively correlated (R = -0.42, P = 0.01) with phosphorylation of eIF2α. Such regulation of protein synthesis will result in variable efficiency of transfer of absorbed EAA to milk protein and is incompatible with the assumption that a single nutrient limits protein synthesis that is encoded in current diet formulation strategies.
Topics: Amino Acids, Essential; Animal Nutritional Physiological Phenomena; Animals; Cattle; Cell Line; Dietary Supplements; Eukaryotic Initiation Factor-2; Female; Isoleucine; Lactation; Leucine; Mammary Glands, Animal; Milk Proteins; Nutritional Requirements; Phosphorylation; Signal Transduction; TOR Serine-Threonine Kinases
PubMed: 22298573
DOI: 10.3945/jn.111.152595