Disease relevance of leucine

• Diabetes mellitus associated with the A-->G mutation at position 3243 of mitochondrial leucine transfer RNA represents a subtype of diabetes found in both patients with IDDM and patients with NIDDM in Japan [1].
• The complete form of X-linked congenital stationary night blindness is caused by mutations in a gene encoding a leucine-rich repeat protein [2].
• Reduced maximal levels of derepression of the isoleucine-valine and leucine enzymes in hisT mutants of Salmonella typhimurium [3].
• Human T-cell leukaemia virus type I (HTLV-I) Tax protein increases the DNA binding of many cellular transcription factors that contain a basic region-leucine zipper (bZIP) DNA-binding domain. bZIP domains comprise a leucine-rich dimerization motif and a basic region that mediates DNA contact [4].
• Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease [5].

Psychiatry related information on leucine

• Interestingly, the Leu102 allele was also carried by some unaffected relatives of 3 patients with CJD with congophilic kuru plaques but with no apparent familial occurrence of a similar neurological disorder [6].
• Mutational analysis of the tau coding region identified a C-to-T change in exon 10 that resulted in the conversion of proline to a leucine (P301L) that segregated with frontotemporal dementia in this family [7].
• BACKGROUND: Three affected individuals are described from a small English kindred with early-onset autosomal dominant familial Alzheimer disease (FAD) caused by a leucine-to-valine change at codon 153 (L153V) of the presenilin 1 (PSEN1) gene [8].
• Significantly low values for threonine, alanine, isoleucine, leucine, lysine and histidine were found in the Huntington's chorea patients [9].
• Recessive mutations within human MLC1 cause megalencephalic leukoencephalopathy with subcortical cysts (MLC), whereas a missense mutation resulting in a methionine substitution within a transmembrane leucine string of MLC has been implicated in catatonic schizophrenia in a large pedigree [10].

High impact information on leucine

• TLR4 belongs to a family of innate immunity receptors that possess a large extracellular domain of leucine-rich repeats, a single trans-membrane segment, and a smaller cytoplasmic signaling region that engages the adaptor protein MyD88 [11].
• We find that the EGFR kinase domain can be activated by increasing its local concentration or by mutating a leucine (L834R) in the activation loop, the phosphorylation of which is not required for activation [12].
• The surviving jawless vertebrates, lampreys and hagfish, instead solved the receptor diversification problem by the recombinatorial assembly of leucine-rich-repeat genetic modules to encode variable lymphocyte receptors [13].
• We report that RPM-1 negatively regulates a p38 MAP kinase pathway composed of the dual leucine zipper-bearing MAPKKK DLK-1, the MAPKK MKK-4, and the p38 MAP kinase PMK-3 [14].
• We constructed a complete, 4.2-Mb physical map across the genetically implicated disease-gene region, identified 28 putative genes (Fig. 1) and resequenced all or part of 21 genes before identifying presumptive mutations in one copy of the leucine-rich, glioma-inactivated 1 gene (LGI1) in each of five families with ADPEAF [15].

Chemical compound and disease context of leucine

• We show here that PrP codon 102 is linked to the putative gene for the syndrome in two pedigrees, providing the best evidence to date that this familial condition is inherited despite also being infectious, and that substitution of leucine for proline at PrP codon 102 may lead to the development of Gerstmann-Sträussler syndrome [16].
• The ratio of plasma alpha amino-n-butyric acid to leucine was raised in patients with both alcohol-related and nonalchol-related liver disease [17].
• In summary, in IDDM: (a) Peripheral hyperinsulinemia is required to normalize both fasting leucine metabolism and blood glucose concentrations [18].
• Local hyperinsulinemia increased (P < 0.05) the rates of inward transport of leucine, lysine, and alanine, from 164 +/- 22 to 200 +/- 25, from 126 +/- 11 to 221 +/- 30, and from 403 +/- 64 to 595 +/- 106 nmol/min per 100 ml leg, respectively [19].
• These studies define the molecular basis of the Bernard-Soulier syndrome within this family and demonstrate that structural integrity of a leucine-rich repeat is necessary for normal function of the glycoprotein Ib-IX-V receptor complex and, possibly, for normal platelet morphology [20].

Biological context of leucine

• The predicted arginine to leucine mutation (Arg554Leu) was proven by amino acid sequence analysis of amyloid fibril protein isolated from postmortem kidney of an affected individual [21].
• We show here that a plasmid containing a cloned gene coding for a yeast leucine tRNA comes under developmental control when injected into cleaving eggs [22].
• Two additional patients have been identified with point mutations that change the same arginine residue to either a histidine or a leucine [23].
• Nucleotide sequence of yeast LEU2 shows 5'-noncoding region has sequences cognate to leucine [24].
• Sequencing of the 5'-noncoding region showed that at -151 there is an open reading frame of 23 codons of which six are for leucine [24].

Anatomical context of leucine

• In contrast, the uptake of L-leucine by islet cells was not affected by any of the IgG fractions [25].
• Ribosomes containing wild-type proteins and U1469 mutant 16S rRNA misincorporate leucine in vitro at elevated levels, comparable to that of some typical S4 ram ribosomes [26].
• We screened 11,000 enhancer trap lines, isolated several expressing beta-galactosidase in small subsets of muscle fibers prior to innervation, and identified two of these as inserts in connectin and Toll, members of the leucine-rich repeat gene family [27].
• A human CSF-1 receptor containing an "activating" mutation in its extracellular domain (serine for leucine 301) induced morphologic transformation, anchorage-independent growth, and tumorigenicity in mouse NIH 3T3 cells [28].
• A critical component of the innate immune system, TLRs utilize leucine-rich-repeat motifs for ligand binding and a shared cytoplasmic domain to recruit the adaptors MyD88, TRIF, TIRAP, and/or TRAM for downstream signaling [29].

Associations of leucine with other chemical compounds

• However, protein-polysaccharide fractions with nearly 40% of the incorporated glucosamine and only 5% mannose and 1% leucine were insensitive to inhibition by tunicamycin [30].
• Sequencing revealed that one mutant allele contains a T----C transition changing a leucine to a proline; another NF1 allele harbors a C----T transition changing an arginine to a stop codon [31].
• All mutations occur in the same base pair of exon 6 and result in the substitution of an uncharged amino acid (leucine or glutamine) for Arg271 in the mature protein [32].
• The pattern of cleavage products and sequence analysis of one fragment indicated that the first scission occurred between leucine 6 and lysine 7 [33].
• The addition of low concentrations of cycloheximide (33-100 ng/ml) at any time after the end of the lag phase brings about a rapid reduction (within 1-2 hr) of the rate constant for entry into S phase by an amount that is proportional to the inhibition of leucine incorporation [34].

Gene context of leucine

• The A. thaliana disease resistance gene RPS2 encodes a protein containing a nucleotide-binding site and leucine-rich repeats [35].
• The yeast SUP53 gene encodes a leucine-inserting amber suppressor tRNA [36].
• We cloned the SNI1 gene and found that it encodes a leucine-rich nuclear protein [37].
• Mutations in Drosophila scribble (scrib), which encodes a multi-PDZ (PSD-95, Discs-large and ZO-1) and leucine-rich-repeat protein, cause aberrant cell shapes and loss of the monolayer organization of embryonic epithelia [38].
• This giant protein comprises an amino-terminal 700-residue leucine-rich region, four RanBP1-homologous (refs 9, 10) domains, eight zinc-finger motifs similar to those of NUP153 (refs 11, 12), and a carboxy terminus with high homology to cyclophilin [39].

Analytical, diagnostic and therapeutic context of leucine

• From the sequence analysis, the previously unidentified tRNA has been shown to have an anticodon sequence (5'-UAG-3') corresponding to a leucine codon [40].
• Site-directed mutagenesis and amino-acid sequencing localized the site of frameshifting to a UUA leucine codon near the 5' end of the overlap [41].
• The three-dimensional structure of the basic/helix-loop-helix/leucine zipper domain of the transcription factor Max complexed with DNA has been determined by X-ray crystallography at 2.9 A resolution [42].
• The incorporation of 3H-labeled leucine by human placental tissue in vitro into pLRF was determined by purification on carboxymethyl-cellulose and specific immunoprecipitation of the 3H-labeled pLRF [43].
• Their rates of VLDL and LDL metabolism were measured by endogenously labeling apoB, the protein component of VLDL and LDL, by an intravenous infusion of deuterated leucine [44].

References