Disease relevance of Isoleucine

• Initiator tRNA from yeast (tRNAMeti) was quantitatively misaminoacylated with L-isoleucine using isoleucyl-tRNA synthetase from Escherichia coli [1].
• We conducted a two center, double-blind, placebo-controlled treatment trial with oral branched chain amino acids (BCAA) (L-leucine 12 g, L-isoleucine 8 g, and L-valine 6.4 g daily) or L-threonine (4 g daily) with pyridoxal phosphate (160 mg daily) for six months in patients with amyotrophic lateral sclerosis (ALS) [2].
• BACKGROUND: The significance of plasma L-alloisoleucine, which is derived from L-isoleucine in vivo, for diagnosis of maple syrup urine disease (MSUD) was examined [3].
• Export of L-isoleucine from Corynebacterium glutamicum: a two-gene-encoded member of a new translocator family [4].
• Clostridium difficile strain CDC A-567 was cultured in Trypticase (BBL Microbiology Systems)-yeast-salt broth supplemented with 0.2% L-leucine, L-norleucine, L-isoleucine, L-tyrosine, or L-tryptophan [5].

Psychiatry related information on Isoleucine

• The derivatization reactions of the four amino acids, L-valine, L-isoleucine, L-leucine and L-phenylalanine, with n-butanol and trifluroacetic anhydride were investigated and the optimum reaction conditions, including reaction time and temperature, were obtained and used for the determination of the amino acids in plasma samples [6].

High impact information on Isoleucine

• Valyl-tRNA synthetase (ValRS) strictly discriminates the cognate L-valine from the larger L-isoleucine and the isosteric L-threonine by the tRNA-dependent "double sieve" mechanism [7].
• The present crystal structures of the synthetase in complexes with L-isoleucine and L-valine demonstrate that the first sieve is on the aminoacylation domain containing the Rossmann fold, whereas the second, editing sieve exists on a globular beta-barrel domain that protrudes from the aminoacylation domain [8].
• A 3-hr exposure of L5178Y cells to media lacking L-isoleucine, an essential amino acid for cell growth, prior to MTX exposure inhibited [3H]thymidine incorporation by 37%, decreased subsequent MTXPG formation by 62%, and increased subsequent cloning in drug-free medium to control levels [9].
• When expressed in Xenopus oocytes, the encoded protein designated LAT3 (L-type amino acid transporter 3) transported neutral amino acids such as l-leucine, l-isoleucine, l-valine, and l-phenylalanine [10].
• The enzyme showed high substrate specificity to NAD (Km = 13.0 mM) and L-penicillamine (Km = 6.5 mM); other nucleotides such as NADP, NAD(P)H, AMP, ADP, and ADP-ribose did not substitute for NAD, and L-valine, L-cysteine, L-homocysteine, L-cystine, L-leucine, and L-isoleucine did not serve as the substrate [11].

Chemical compound and disease context of Isoleucine

• Nonprotein amino acid furanomycin was found to bind with Escherichia coli isoleucyl-tRNA synthetase (IleRS) almost as tightly as the substrate L-isoleucine [12].
• NMR analyses of the conformations of L-isoleucine and L-valine bound to Escherichia coli isoleucyl-tRNA synthetase [13].
• Labelling of L-isoleucine tRNA ligase from Escherichia coli with L-isoleucyl-bromomethyl ketone [14].
• Construction of L-lysine-, L-threonine-, and L-isoleucine-overproducing strains of Corynebacterium glutamicum [15].
• In isoleucyl tRNA synthetase from Escherichia coli, phenylglyoxal inhibits activation of L-isoleucine to isoleucyl adenylate [16].

Biological context of Isoleucine

• Case I states that liganding of the activator sites must percede substrate-binding at the active site, and Case II states that the activator site liganding is required solely for reactivation of the L-isoleucine-inhibited enzyme [17].
• Studies on the biosynthesis of paraherquamide: concerning the mechanism of the oxidative cyclization of L-isoleucine to beta-methylproline [18].
• In the presence of L-leucine or L-isoleucine, however, which both inhibited L-NNA uptake, the IC50 of L-NNA was increased from 1.2 microM to 37 microM but the inhibitory actions of L-NMA remained unaffected [19].
• Acylation of the (hydroxethyl)hydrazine dipeptide isostere with the L-tert-leucine derivative 29 increased the oral bioavailability significantly when compared to the corresponding L-valine or L-isoleucine derivatives [20].
• In order to identify the system responsible for L-isoleucine export, we have used transposon mutagenesis to isolate mutants of C. glutamicum sensitive to the peptide isoleucyl-isoleucine [4].

Anatomical context of Isoleucine

• Insulin release evoked by 2-ketoisocaproate from isolated rat pancreatic islets was inhibited by L-valine, L-isoleucine, L-norvaline, and L-norleucine [21].
• In vitro experiments showed that piperine (25-100 microM) significantly stimulated gamma-glutamyl transpeptidase (gamma-GT, EC 2.3.2.2.) activity, enhanced the uptake of radiolabelled L-leucine, L-isoleucine and L-valine, and increased lipid peroxidation in freshly isolated epithelial cells of rat jejunum [22].
• During strict metabolic balance, the plasma L-allo-isoleucine/L-isoleucine ratio correlates inversely with the residual activity of the branched-chain 2-oxoacid dehydrogenase in fibroblasts and thus constitutes a relevant in vivo parameter of the severity of the metabolic defect in MSUD patients [23].
• The fate of leucine nitrogen in the central nervous system was investigated by incubating rat cerebral cortex slices in the presence of 0.5 mM each of L-[15N]-leucine, L-isoleucine, and L-valine [24].
• Oral administrations of taurine (4-7 g/kg/day, for 3 days) prevented the stress-induced decline of adrenaline in the adrenal gland and this preventive effect could not be duplicated by the administration of L-isoleucine or DL-methionine [25].

Associations of Isoleucine with other chemical compounds

• In addition to the previously characterized osmotic shock-sensitive LS (L-leucine-specific) and LIV-I (L-leucine; L-isoleucine-, and L-valine-specific) activities, a third system (designated LIV-II) has been detected, confirming a report by Rahmanian et al [26].
• Threonine deaminase possesses two L-isoleucine binding sites (Kd equals 3.6 muM) and one L-valine binding site (Kd equals 26 muM); the binding of these ligands appear competitive [17].
• However, in the presence of isoleucyl adenylate tightly bound to the amino acid activation site of IleRS, no TRNOE for L-isoleucine or L-valine was observed [13].
• The efficacy of icofungipen in mice and rats was not influenced by concomitant administration of equimolar amounts of L-isoleucine, which was shown to antagonize its antifungal activity in vitro [27].
• We studied the effects of increasing dietary concentrations of each of the following amino acids on growth, feed intake, feed conversion ratio and composition of gain in rainbow trout in six dose-response experiments: L-lysine, L-tryptophan, L-histidine, L-valine, L-leucine and L-isoleucine [28].

Gene context of Isoleucine

• 2-Methylbutyryl-coenzyme A dehydrogenase deficiency: a new inborn error of L-isoleucine metabolism [29].
• In our experimental conditions, L-isoleucine, described to stimulate beta-defensin in bovine epithelial cells, did not exert any effect either on hBD-2 and hBD-3 transcripts or MIP-3alpha protein [30].
• The same genes, ilvBNCD, overexpressed in an ilvA deletion mutant which is unable to synthesize L-isoleucine increased the concentration of this amino acid to 58 mM [31].
• Effects of an Escherichia coli ilvA mutant gene encoding feedback-resistant threonine deaminase on L-isoleucine production by Brevibacterium flavum [32].
• Disruption of the B. flavum ilvC gene by a kanamycin resistance cassette resulted in L-isoleucine and L-valine auxotrophy [33].

Analytical, diagnostic and therapeutic context of Isoleucine

• When L-leucine was administered during perfusion of L-isoleucine, L-leucine-induced release of glucagon was inhibited, that of insulin was augmented, and the insulin off-response prevailed [34].
• The random coil goes to beta transition of copolymers of L-lysine and L-isoleucine: potentiometric titration and circular dischroism studies [35].
• Free amino acid concentrations in both plasma and milk from three lactating dairy cows were studied after intravenous infusions of L-isoleucine at 62, 300, 380, and 840 mumol/kg of body weight [36].
• The free radicals produced by gamma-radiolysis of polycrystalline amino acids (L-valine, L-leucine, L-isoleucine and L-proline) at room temperature in the absence of air were investigated by spin trapping with 2-methyl-2-nitrosopropane (MNP) [37].

References