Disease relevance of Isoleucine

• Variant-sequence transthyretin (isoleucine 122) in late-onset cardiac amyloidosis in black Americans [1].
• Replacing the isoleucine at amino-acid position three of bacteriophage T4 lysozyme causes changes in the thermodynamic stability of the protein that are directly related to the hydrophobicity of the substituted residue [2].
• By contrast, other amino-acid changes in the same region do not affect CD4 binding but restrict viral tropism: virions containing isoleucine substitutions at position 425 lose their ability to infect a monocyte cell line (U937 cells) but can still infect T-lymphocyte cell lines (CEM, SUP-T1) and activated human peripheral blood lymphocytes [3].
• With the class I Escherichia coli isoleucine tRNA synthetase, which activates isoleucine and occasionally misactivates valine, as an example, a rationally chosen mutant enzyme was constructed that lacks entirely its normal strong ability to distinguish valine from isoleucine by the initial amino acid recognition sieve [4].
• For GSTP1, the data were suggestive of a trend of increasing risk with higher numbers of codon 105 valine alleles (compared with isoleucine alleles); a 1.97-fold increased risk of breast cancer (95% CI = 0.77-5.02) was associated with valine/valine homozygosity [5].

Psychiatry related information on Isoleucine

• Here we describe a new substitution of methionine 146 for isoleucine that co-segregates with Alzheimer's disease with age of the onset in the early forties [6].
• A valine to isoleucine mutation at residue 180 was identified in a French patient with Creutzfeldt-Jakob disease (CJD) [7].
• Peptides that regulate food intake: effect of peptide histidine isoleucine on consummatory behavior in rats [8].
• The major control locus, designated ilvO, is located before ilvG forming an ilvOGEDA transcriptional unit that is multivalently repressed by isoleucine, valine and leucine [9].
• 5. Patients with Huntington's chorea showed reduced fasting plasma concentrations of leucine, isoleucine and valine [10].

High impact information on Isoleucine

• The synthesis of histones and DNA was examined in BHK cells arrested in G1 by isoleucine starvation and in cells progressing into the S phase upon isoleucine refeeding [11].
• In isoleucine-depleted medium, wild-type SV40-transformed cells had fewer forks per unit length than those few nontransformed cells (1-3% of the population) which continued DNA replication [12].
• A non-conserved isoleucine in the amino-terminal flanking region covers a hydrophobic patch and stabilizes the WW domain of human YAP65 in vitro [13].
• Affected individuals are heterozygous for point mutations in the lysozyme gene that cause substitution of highly conserved residues, namely threonine for isoleucine at position 56 in one family, and histidine for aspartic acid at residue 67 in the other [14].
• Comparison of the human mitochrondial DNA sequence of the cytochrome oxidase subunit II gene and the sequence of the corresponding beef heart protein shows that UGA is used as a tryptophan codon and not as a termination codon and suggests that AUA may be a methionine and not an isoleucine codon [15].

Chemical compound and disease context of Isoleucine

• BACKGROUND: After the age of 60, isolated cardiac amyloidosis is four times more common among blacks than whites in the United States; 3.9 percent of blacks are heterozygous for an amyloidogenic allele of the normal serum carrier protein transthyretin in which isoleucine is substituted for valine at position 122 (Ile 122) [1].
• Substitution of leucine for isoleucine in a sequence highly conserved among retroviral envelope surface glycoproteins attenuates the lytic effect of the Friend murine leukemia virus [16].
• The growth rate of rodent embryonic neuroblasts and human neuroblastoma cell lines is regulated in part by autocrine or paracrine actions of neuropeptides of the family that includes vasoactive intestinal peptide (VIP), peptide histidine isoleucine (PHI), and pituitary adenylate cyclase-activating peptide (PACAP) [17].
• Using homopolymeric units of either isoleucine, leucine, valine or alanine to replace the natural core segment of the Escherichia coli alkaline phosphatase signal peptide, the hydrophobicity requirements for export and processing were delineated [18].
• The mutation in which the isoleucine residue at position 8 of the OmpA signal sequence of Escherichia coli was replaced with a neutral polar residue, asparagine, resulted in a defective signal peptide [19].

Biological context of Isoleucine

• The anticodons for methionine and isoleucine tRNAs differ by a single nucleotide, and changing this nucleotide in an isoleucine tRNA is sufficient to change aminoacylation specificity to methionine [20].
• An analysis of cycling cell populations (exponentially growing CHO cultures) and noncycling CHO cells arrested in the G1 phase by growth in isoleucine-free medium demonstrated the potential of the technique [21].
• Random mutations were introduced by cassette mutagenesis into a ten-amino-acid segment of Ile-tRNA synthetase that was predicted to be involved in the formation of the binding site for isoleucine [22].
• These consist of an unusually large, unique DNA-binding and dimerization domain, as well as a novel, isoleucine-rich activation domain [23].
• Although ectopic expression of wild-type p53 blocked cells in the G1 phase of the cell cycle, G1 arrest by isoleucine starvation, in a manner independent of p53, did not confer susceptibility to apoptosis [24].

Anatomical context of Isoleucine

• NK3-specific natural killer cells are selectively inhibited by Bw4-positive HLA alleles with isoleucine 80 [25].
• Substitution of isoleucine in cIL-10 with alanine, which corresponds to the vIL-10 residue, abrogates immunostimulatory activity for thymocytes, mast cells, and alloantigenic responses while preserving immunosuppressive activity for inhibition of interferon gamma production and prolongation of cardiac allograft survival [26].
• After the administration of erythrocytes, isoleucine or saline was administered i.v. for 6 hours [27].
• The net efflux of nearly all amino acids by the portal-drained viscera increased significantly less (P less than 0.001) in the isoleucine group [27].
• Role of peptide histidine isoleucine in relaxation of cat lower esophageal sphincter [28].

Associations of Isoleucine with other chemical compounds

• A point mutation in STM2, resulting in the substitution of an isoleucine for an asparagine (N141l), was identified in affected people from Volga German AD kindreds [29].
• The abnormal behavior of unc-17(e245) mutants, which have a glycine-to-arginine substitution in a transmembrane domain, is markedly improved by a mutant synaptobrevin with an isoleucine-to-aspartate substitution in its transmembrane domain [30].
• At nucleotide 2,317 we identified a homozygous A for G point mutation that predicts an isoleucine (ATT) for valine (GTT) substitution at amino acid 729 [31].
• About two-thirds of the fibril subunit protein was found to contain an amino acid substitution at position 84 where the normal isoleucine residue has been replaced by serine [32].
• The isoleucine for valine substitution at amino acid 729 impairs the function of the hGR and is the likely cause of primary cortisol resistance in this subject [31].

Gene context of Isoleucine

• Further, in isoleucine-deprived cells, Myc induces apoptosis without altering cdk activity [33].
• The mutant carries two mutations in CMD1, isoleucine 100 is changed to asparagine and glutamic acid 104 is changed to valine [34].
• A second mutation, a homoplasmic T-->A transition at nucleotide position 14596 in the ND6 gene, resulted in the substitution of a methionine for the isoleucine at amino acid residue 26 [35].
• Among the other 11 unique mutations, 8 were small deletions or insertions predicted to cause frameshifts, 1 was a mutation to a stop codon, 1 was a missense mutation, and 1 was predicted to cause insertion of an isoleucine in the hect domain of the UBE3A protein, which functions in E2 binding and ubiquitin transfer [36].
• The presence of a codon for isoleucine at the residues corresponding to codon 255 of rat CPA1 cDNA strongly suggests that the A form of human carboxypeptidase has been isolated [37].

Analytical, diagnostic and therapeutic context of Isoleucine

• Complete sequence analysis of one SSA preparation revealed the presence of a new variant Pa (TTr) molecule with a single amino acid substitution of isoleucine for valine at position 122 [38].
• Splanchnic urea production increased more in the control group than in the isoleucine group (P less than 0.05) [27].
• Intravenous infusion of low doses of vasoactive intestinal polypeptide, peptide histidine valine-42, and peptide histidine methionine (and the rat equivalent, peptide histidine isoleucine) into anesthetized rats caused a reduction in net absorption of fluid from the small intestine [39].
• To estimate the relative importance of this key hydrophobic contact in polymer formation we have generated a polymerizing Hb with isoleucine at the beta 6 position (beta E6I) by site-directed mutagenesis [40].
• Direct sequencing of DNA segments amplified by the polymerase chain reaction (PCR) that encode the exons of the lecithin-cholesterol acyltransferase gene led to the identification of a homozygous mutation resulting in the substitution of threonine at codon 123 for an isoleucine residue in both individuals [41].

References