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Current Protein & Peptide Science 2019Branched chain amino acids are the essential nutrients for humans and many animals. As functional amino acids, they play important roles in physiological functions,... (Review)
Review
Branched chain amino acids are the essential nutrients for humans and many animals. As functional amino acids, they play important roles in physiological functions, including immune functions. Isoleucine, as one of the branched chain amino acids, is also critical in physiological functions of the whole body, such as growth, immunity, protein metabolism, fatty acid metabolism and glucose transportation. Isoleucine can improve the immune system, including immune organs, cells and reactive substances. Recent studies have also shown that isoleucine may induce the expression of host defense peptides (i.e., β-defensins) that can regulate host innate and adaptive immunity. In addition, isoleucine administration can restore the effect of some pathogens on the health of humans and animals via increasing the expression of β-defensins. Therefore, the present review will emphatically discuss the effect of isoleucine on immunity while summarizing the relationship between branched chain amino acids and immune functions.
Topics: Animals; Disease; Humans; Immunity; Isoleucine
PubMed: 30843485
DOI: 10.2174/1389203720666190305163135 -
Cell Metabolism Nov 2023Low-protein diets promote health and longevity in diverse species. Restriction of the branched-chain amino acids (BCAAs) leucine, isoleucine, and valine recapitulates...
Low-protein diets promote health and longevity in diverse species. Restriction of the branched-chain amino acids (BCAAs) leucine, isoleucine, and valine recapitulates many of these benefits in young C57BL/6J mice. Restriction of dietary isoleucine (IleR) is sufficient to promote metabolic health and is required for many benefits of a low-protein diet in C57BL/6J males. Here, we test the hypothesis that IleR will promote healthy aging in genetically heterogeneous adult UM-HET3 mice. We find that IleR improves metabolic health in young and old HET3 mice, promoting leanness and glycemic control in both sexes, and reprograms hepatic metabolism in a sex-specific manner. IleR reduces frailty and extends the lifespan of male and female mice, but to a greater degree in males. Our results demonstrate that IleR increases healthspan and longevity in genetically diverse mice and suggests that IleR, or pharmaceuticals that mimic this effect, may have potential as a geroprotective intervention.
Topics: Male; Female; Animals; Mice; Isoleucine; Longevity; Health Promotion; Mice, Inbred C57BL; Amino Acids, Branched-Chain
PubMed: 37939658
DOI: 10.1016/j.cmet.2023.10.005 -
Molecular Nutrition & Food Research Oct 2023Obesity induced by high-fat diet (HFD) can cause lipid metabolism disorders and cognitive impairment. Isoleucine restriction can effectively alleviate lipid metabolism...
SCOPE
Obesity induced by high-fat diet (HFD) can cause lipid metabolism disorders and cognitive impairment. Isoleucine restriction can effectively alleviate lipid metabolism disorders caused by HFD but the underlying mechanisms on cognition are unknown.
METHODS AND RESULTS
Thirty 3-month-old C57BL/6J mice are divided equally into the following groups: the control group, HFD group, and HFD Low Ile group (67% reduction in isoleucine in high fat feeds). Feeding for 11 weeks with behavioral testing, which shows that isoleucine restriction attenuates HFD-induced cognitive dysfunction. As observed by staining, isoleucine restriction inhibits HFD-induced neuronal damage and microglia activation. Furthermore, isoleucine restriction significantly increases the relative abundance of gut microbiota, decreases the proportion of Proteobacteria, and reduces the levels of lipopolysaccharide (LPS) in serum and brain. Isoleucine restriction reduces protein expression of TLR4/MyD88/NF-κB signaling pathway and inhibits upregulation of proinflammatory cytokine genes and protein expression in mice brain. In addition, isoleucine restriction significantly improves insulin resistance in the brain as well as synaptic plasticity impairment.
CONCLUSION
Isoleucine restriction may be a potential intervention to reduce HFD-induced cognitive impairment by altering gut microbiota, reducing neuroinflammation, insulin resistance, and improving synaptic plasticity in mice brain.
Topics: Mice; Animals; Gastrointestinal Microbiome; Isoleucine; Mice, Obese; Insulin Resistance; Mice, Inbred C57BL; Cognitive Dysfunction; Brain; Lipid Metabolism Disorders; Diet; Diet, High-Fat
PubMed: 37658490
DOI: 10.1002/mnfr.202200767 -
Trends in Cardiovascular Medicine Feb 2003The sympathetic nervous system controls the force and rate of contraction of the heart. The rapid response to stress and exercise mediated by increased sympathetic... (Review)
Review
The sympathetic nervous system controls the force and rate of contraction of the heart. The rapid response to stress and exercise mediated by increased sympathetic nervous system (SNS) activity requires the coordinated regulation of several ion channels in response to activation of beta-adrenergic receptors. The microenvironment of target channels is mediated by the assembly of macromolecular signaling complexes in which targeting proteins recruit phosphatases and kinases and in turn bind directly to the channel protein via highly conserved leucine/isoleucine zippers (LIZs). Disruption of local signaling by disease-associated LIZ mutations unbalances the physiologic response to SNS stimulation and increases the risk of arrhythmia in mutation carriers.
Topics: Arrhythmias, Cardiac; Heart; Humans; Ion Channels; Isoleucine; Leucine Zippers; Macromolecular Substances; Myocardial Contraction; Receptors, Adrenergic, beta; Sympathetic Nervous System
PubMed: 12586439
DOI: 10.1016/s1050-1738(02)00211-6 -
Phytochemistry Sep 2010Our understanding of plant defensive mechanisms against herbivore and pathogen attack has significantly increased over the past decade. The complex cascade of defensive... (Review)
Review
Our understanding of plant defensive mechanisms against herbivore and pathogen attack has significantly increased over the past decade. The complex cascade of defensive events is initiated and controlled by a network of interacting plant hormones. Especially, the conjugate of jasmonate and isoleucine is a major regulator which controls gene expression and production of secondary metabolites after (a)biotic challenges. This review offers a survey of both natural and synthetic mimetics of the natural hormone which can be used for a selective manipulation and the study of the plant's secondary metabolism.
Topics: Cyclopentanes; Isoleucine; Plant Cells; Plant Growth Regulators; Plant Physiological Phenomena; Plants; Signal Transduction; Structure-Activity Relationship
PubMed: 20570297
DOI: 10.1016/j.phytochem.2010.04.027 -
Biotechnology Letters Sep 2023To explore an L-isoleucine (Ile)-induced biosensor for down-regulation of Ile synthesis pathway and enhancement of 4-hydroxyisoleucine (4-HIL) production in...
OBJECTIVES
To explore an L-isoleucine (Ile)-induced biosensor for down-regulation of Ile synthesis pathway and enhancement of 4-hydroxyisoleucine (4-HIL) production in Corynebacterium glutamicum SN01.
RESULTS
Four Ile-induced riboswitches (IleRSN) with different strength were screened from mutation library based on TPP riboswitch. Firstly, IleRSN were integrated into the chromosome of strain SN01 immediately upstream of ilvA gene. The 4-HIL titer of strains carrying P-driven IleRS1 or IleRS3 (14.09 ± 1.07, 15.20 ± 0.93 g 4-HIL L) were similar with control strain S-I (15.73 ± 2.66 g 4-HIL L). Then, another copy of IleRS3-ilvA was integrated downstream of the chromosomal cg0963 gene in SN01-derived strain D-RS with down-regulated L-lysine (Lys) biosynthesis. The Ile supply and 4-HIL titer increased in ilvA two-copy strains KIRSA-3-I and KIRSA-3-I, and Ile concentration was maintained less than 35 mmol L under the control of IleRS3 during fermentation. The resulting strain KIRSA-3-I produced 22.46 ± 0.96 g 4-HIL L.
CONCLUSION
The screened IleRS was effective in the dynamic down-regulation of Ile synthesis pathway in C. glutamicum, and IleRSN with different strength can be applied in various conditions.
Topics: Corynebacterium glutamicum; Riboswitch; Isoleucine; Metabolic Engineering
PubMed: 37395871
DOI: 10.1007/s10529-023-03407-6 -
Chemical Communications (Cambridge,... Dec 2019Chemical shifts are often the only nuclear magnetic resonance parameter that can be obtained for challenging macromolecular systems. Here we present a framework to...
Chemical shifts are often the only nuclear magnetic resonance parameter that can be obtained for challenging macromolecular systems. Here we present a framework to derive the conformational sampling of isoleucine side chains from C chemical shifts and demonstrate that side-chain conformations in a low-populated folding intermediate can be determined.
Topics: Carbon Isotopes; Density Functional Theory; Isoleucine; Nuclear Magnetic Resonance, Biomolecular; Protein Conformation; Proteins
PubMed: 31642826
DOI: 10.1039/c9cc06496f -
Toxicon : Official Journal of the... Aug 2023Previous studies have identified some key amino acid residues in scorpion toxins blocking potassium channels. In particular, the most numerous toxins belonging to the...
Previous studies have identified some key amino acid residues in scorpion toxins blocking potassium channels. In particular, the most numerous toxins belonging to the α-KTx family and affecting voltage-gated potassium channels (K) present a conserved K-C-X-N motif in the C-terminal half of their sequence. Here, we show that the X position of this motif is almost always occupied by either methionine or isoleucine. We compare the activity of three pairs of peptides that differ just by this residue on a panel of K1 channels and find that toxins bearing methionine affect preferentially K1.1 and 1.6 isoforms. The refined K-C-M/I-N motif stands out as the principal structural element of α-KTx conferring high affinity and selectivity to K channels.
Topics: Animals; Potassium Channels, Voltage-Gated; Scorpion Venoms; Amino Acid Sequence; Isoleucine; Methionine; Racemethionine; Potassium Channel Blockers; Scorpions
PubMed: 37301298
DOI: 10.1016/j.toxicon.2023.107181 -
Journal of Chromatography. B,... Jul 2001The initial catabolic steps of isoleucine by mammals has been misunderstood and misapprehended in the scientific literature for many years. The suggestion that the... (Review)
Review
The initial catabolic steps of isoleucine by mammals has been misunderstood and misapprehended in the scientific literature for many years. The suggestion that the interconversion of isoleucine and alloisoleucine occurs through the keto-enol racemization of their respective transaminated alpha-keto acids was first tentatively advanced by Alton Meister in the early 1950s, and accepted without hard confirming evidence by many authors. It will be shown in this brief review that isoleucine is converted to alloisoleucine with conservation of a 15N label denying the intermediacy of the alpha-keto acids, and that alloisoleucine arises as an unavoidable consequence of isoleucine transamination.
Topics: Isoleucine
PubMed: 11482734
DOI: 10.1016/s0378-4347(01)00111-6 -
FASEB Journal : Official Publication of... Aug 2022Non-alcoholic steatohepatitis (NASH) is associated with a disturbed metabolism in liver, insulin resistance, and excessive accumulation of ectopic fat. Branched-chain...
Intervention with isoleucine or valine corrects hyperinsulinemia and reduces intrahepatic diacylglycerols, liver steatosis, and inflammation in Ldlr-/-.Leiden mice with manifest obesity-associated NASH.
Non-alcoholic steatohepatitis (NASH) is associated with a disturbed metabolism in liver, insulin resistance, and excessive accumulation of ectopic fat. Branched-chain amino acids (BCAAs) may beneficially modulate hepatic lipids, however, it remains unclear whether individual BCAAs can attenuate already established NASH and associated oxidative-inflammatory stress. After a 26 weeks run-in on fast food diet (FFD), obese Ldlr-/-.Leiden mice were treated for another 12 weeks with either valine or isoleucine (3% of FFD) and then compared to FFD controls. Valine and isoleucine did not affect obesity, dyslipidemia, gut permeability, or fecal fatty acid excretion, but significantly reduced hyperinsulinemia. Valine and isoleucine reduced ALT, CK18-M30, and liver steatosis with a particularly pronounced suppression of the microvesicular component (-61% by valine and -71% by isoleucine). Both BCAAs decreased intrahepatic diacylglycerols and 4-hydroxynonenal immunoreactivity, a marker for oxidative stress-induced lipid peroxidation. Functional genomics analysis demonstrated that valine and isoleucine affected BCAA metabolism genes, deactivated master regulators of anabolic pathways related to steatosis (e.g., SREBPF1), and activated master regulators of mitochondrial biogenesis (e.g., PPARGC1A) and lipid catabolism (e.g., ACOX1, AMPK). This correction of critical metabolic pathways on gene expression level was accompanied by a significant decrease in histological liver inflammation, and suppression of FFD-stimulated cytokine and chemokine proteins KC/CXCL1, MCP-1/CCL2, and MIP-2/CXCL2 and their pathways. In conclusion, dietary intervention with either valine or isoleucine corrected liver diacylglycerols, gene expression of multiple metabolic processes, and reduced NASH histology with profound hepatoprotective effects on oxidative stress and inflammatory proteins.
Topics: Amino Acids, Branched-Chain; Animals; Diglycerides; Hyperinsulinism; Inflammation; Isoleucine; Liver; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Obesity; Valine
PubMed: 35830259
DOI: 10.1096/fj.202200111R