Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “ISOLEUCINE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 163 records · Page 9Linked to original sources

Initial catabolic steps of isoleucine, the R-pathway and the origin of alloisoleucine.

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.

Isoleucine↗

Stereospecificity of the enzymatic dehydrogenation in the biosynthesis of 3-ethylidene-L-azetidine-2-carboxylic acid from isoleucine by Streptomyces cacaoi.

(2RS,3S,4S)-[2-14C,4-3H]Isoleucine and (2S,3S,4R)-[U-14C,4-3H]isoleucine have been prepared by stereospecific syntheses. The addition of these substrates to Streptomyces cacaoi led to the isolation of polyoxins from which 3-ethylidene-L-azetidine-2-carboxylic acid was isolated by hydrolysis. The pro-R hydrogen at C-4 of isoleucine was lost and the pro-S hydrogen was retained in the biosynthesis of 3-ethylidene-L-azetidine-2-carboxylic acid. These results indicate that the enzymatic dehydrogenation of isoleucine to form 3-ethylidene-L-azetidine-2-carboxylic acid involves the antiperiplanar elimination of the hydrogen at C-3 and the pro-R hydrogen at C-4.

Azetidinecarboxylic Acid↗

Energetics of side chain packing in staphylococcal nuclease assessed by exchange of valines, isoleucines, and leucines.

To examine the importance of side chain packing to protein stability, each of the 11 leucines in staphylococcal nuclease was substituted with isoleucine and valine. The nine valines were substituted with leucine and isoleucine, while the five isoleucines, previously substituted with valine, were substituted with leucine and methionine. These substitutions conserve the hydrophobic character of these side chains but alter side chain geometry and, in some cases, size. In addition, eight threonine residues, previously substituted with valine, were substituted with isoleucine to test the importance of packing at sites normally not occupied by a hydrophobic residue. The stabilities of these 58 mutant proteins were measured by guanidine hydrochloride denaturation. To the best of our knowledge, this is the largest library of single packing mutants yet characterized. As expected, repacking stability effects are tied to the degree of side chain burial. The average energetic cost of moving a single buried methyl group was 0.9 kcal/mol, albeit with a standard deviation of 0.8 kcal/mol. This average is actually slightly greater than the value of 0.7-0.8 kcal/mol estimated for the hydrophobic transfer energy of a methylene from octanol to water. These results appear to indicate that van der Waals interactions gained from optimal packing are at least as important in stabilizing the native state of proteins as hydrophobic transfer effects.

Amino Acid Substitution↗

Biochemical and mass spectrometric evidence for quaternary structure modifications of plant threonine deaminase induced by isoleucine.

Arabidopsis thaliana threonine deaminase (TD) is a tetramer composed of identical approximately 59600 Da subunits. TD activity has been shown to be inhibited by isoleucine. This effect is reversed by a large excess of valine. Nondenaturant gel filtration, polyacrylamide gel electrophoresis, and mass spectrometry experiments demonstrated that binding of isoleucine on TD induces dimerization of the enzyme, whereas tetramerization is restored by addition of a high valine concentration. Nondenaturant gel filtration and electrospray ionization mass spectrometry of the enzyme in the presence of increasing amounts of isoleucine suggest a fast equilibrium between the tetramer and the dimer. Finally, study of TD mutants allowed us to focus on the specific role of each isoleucine-binding site.

Arabidopsis↗

A more complex isoleucine aptamer with a cognate triplet.

The simplest RNA that can meet a column affinity selection for isoleucine was previously defined using selection amplification with decreasing numbers of randomized nucleotides. This simplest UAUU motif was a small asymmetric internal loop. Conserved positions of the loop include isoleucine codon and anticodon triplets (Lozupone C., Changayil, S., Majerfeld, I., and Yarus, M. (2003) RNA (N. Y.) 9, 1315-1322). Using new primer sequences, we now select a somewhat more complex isoleucine binding RNA, requiring 4.7 more bits of information to describe. The newly selected structure is a terminal or hairpin loop of 20 nucleotides, 15 being invariant. An information profile shows that the new binding site contains five short functional loop regions joined by less significant single nucleotide positions. Among the important nucleotides is a conserved isoleucine anticodon, supporting the escaped triplet theory, which posits a stereochemical genetic code originating in RNA amino acid binding sites.

Anticodon↗

Relationship between food consumption and energy and nitrogen utilisation by chicks given varying amounts of standard and leucine-, isoleucine- and valine-deficient diets.

The effect of different amounts of food, varying from below to above the rate of voluntary intake, was studied in chicks using a standard diet and diets containing only half the recommendation concentrations of leucine, isoleucine or valine. Irrespective of diet the body weight gain of the chicks increased with increasing food consumption. The body weight gain of chicks given the leucine-deficient diet was similar to that of chicks given the same amount of the standard diet. In contrast, the body weight gains of chicks given either the valine- or isoleucine-deficient diet were significantly less than that of chicks given the same amount of the standard diet. When the food intakes of the birds were similar the differences in body protein and water contents of the birds fed the different diets reflected differences in body weight gains, whereas body fat content was affected in the reverse manner. Retention and retention rate of dietary energy increased as food consumption increased. This was particularly evident in chicks given the isoleucine-deficient diet, followed by those given the valine-, leucine-deficient and standard diets. For all diets, the amounts of nitrogen retained and nitrogen retention rate (N retained/N consumed) increased in line with body weight gain. The metabolisable energy values of the diets were similar, except for the isoleucine-deficient diet which had a significantly higher metabolisable energy value than the standard valine-deficient diets.

Amino Acids, Essential↗

Increased isoleucine acceptance by sulfur-deficient transfer RNA from Escherichia coli.

Sulfur-deficient tRNA, isolated from Escherichia coli HfrC, rel-, met-, cys-, lambda, after cysteine starvation, was found to have an increased acceptance of isoleucine in proportion to the deficiency of 4-thiouridine. Isoleucine acceptance was not altered in the presence of other amino acids of CTP, and the higher acceptance was observed over a wide range of magnesium, isoleucine, tRNA and enzyme concentrations. The Vmax value for sulfur-deficient tRNA was more than three times greater than observed for normal tRNA. Methylated albumin kieselguhr (MAK) chromatography revealed three isoacceptor peak for normal tRNA, while sulfur-deficient tRNA was missing tRNAile, and exhibited a larger, shifted peaks for tRNA normal tRNA, while sulfur-deficient tRNA was missing tRNAille 2, and exhibited a large shifted peak for tRNAile 3 . Treatment with crude RNA sulfurtransferase both lowered the isoleucine acceptance for sulfur-deficient tRNA to that seen for normal tRNA, and restored the missing isoacceptor on MAK. The possibility that thionucleotides may play a role in the aminoacylation of tRNAile in E. coli is discussed.

Amino Acyl-tRNA Synthetases↗

Growth of Paracoccus denitrificans on [2,3-13C]succinate and [1,4-13C]succinate. II. Isoleucine biosynthesis.

Paracoccus denitrificans was grown on either [2,3-13C]succinate or [1,4-13C]succinate, and extracts were analysed by using gas chromatography-mass spectrometry. The distribution of label in isoleucine indicated that the 2-ketobutyrate required for isoleucine biosynthesis was mainly produced from pyruvate by 2-keto-acid chain elongation (i.e. the 'pyruvate elongation pathway'). Approximately 10% of isoleucine was produced by a second pathway involving propionyl CoA. Threonine and glutamate were not utilized by P. denitrificans as a source of 2-ketobutyrate production for isoleucine biosynthesis under the growth conditions used.

Carbon Isotopes↗

Transductional construction of an isoleucine-producing strain of Serratia marcescens.

Strain GIHVLr6426 was isolated as an isoleucine hydroxamate-resistant mutant from the wild-type strain of Serratia marcescens Sr41. This mutant had high activities of threonine deaminase and acetohydroxyacid synthase, both of which were insensitive to feedback inhibition. Genetic analysis revealed that strain GIHVLr6426 carried two regulatory mutations located in the ilv region. Strain T-693, a threonine-producing strain which was previously reported to carry four regulatory mutations for threonine biosynthesis, had an increased activity of acetohydroxyacid synthase. Transductional analysis revealed that one of the four mutations carried by strain T-693 was responsible for constitutive synthesis of both isoleucine and threonine biosynthetic enzymes. Strain GIHVLr6426 into strain T-693. The constructed strain had the six regulatory mutations for threonine and isoleucine biosyntheses, and produced about 25 mg isoleucine ml-1 in a medium containing sucrose and urea.

Genes, Regulator↗

Serum valine, methionine and isoleucine levels in patients anaesthetized with and without nitrous oxide.

Serum methionine and valine have been assayed microbiologically in 31 patients anaesthetized with and in 13 controls anaesthetized without nitrous oxide. Isoleucine has been similarly assayed in five cases and three controls. The preinduction levels of both methionine and valine were considerably below those of semifasting healthy adults. Serum methionine fell significantly in both groups as did valine and isoleucine in the controls. These findings are attributed to dietary restriction before and during the operation. Serum valine was significantly elevated in patients anaesthetized with nitrous oxide but only in those anaesthetized for 3 h or longer. Isoleucine also was elevated in two of the five cases exposed to nitrous oxide. Reasons are given for attributing these elevated levels to the direct action of nitrous oxide. Valine is entirely and isoleucine is partly catabolized along the adenosylcobalamin dependent propionyl-CoA-succinyl-CoA pathway. It is concluded that their elevated levels are caused by the inactivation of adenosylcobalamin by nitrous oxide thereby inducing the methylmalonyl mutase block in this pathway. It is suggested also that the relief of this block by adenosylcobalamin in pernicious anaemia could provide a possible metabolic basis for the well recognized early subjective improvement encountered in this disease following vitamin B12 therapy.

Adolescent↗

A comprehensive survey on isoleucine biosynthesis pathways in seven epidemic Leptospira interrogans reference strains of China.

Previous studies have indicated that different species of Leptospira synthesize isoleucine via either pyruvate and/or threonine pathways. Seven epidemic Leptospira interrogans reference strains from China belonging to different serovars, together with three saprophytic strains of Leptospira biflexa and Leptospira meyeri, were analysed. The isoleucine biosynthesis properties were studied firstly by measuring the key enzymes of the two pathways, citramalate synthase (CimA, CE4.1.3.-) and threonine deaminase (IlvA, CE4.2.1.16), from cell extracts of the bacteria. Meanwhile, alpha-isopropylmalate synthase (LeuA, CE4.2.1.12), the key enzyme of leucine biosynthesis, was also measured as a control. It was found that all L. interrogans strains synthesized isoleucine via the pyruvate pathway exclusively, but L. biflexa and L. meyeri used both pathways. Dot-Blot and PCR amplification of both cimA and ilvA genes in the corresponding strains provided additional evidence consistent with the data of enzymatic assays. Although it is evident that leptospires' isoleucine biosynthesis may preferentially adapt either to the pyruvate pathway exclusively for pathogens or to the combination of both pyruvate and threonine pathways for saprophytes, broader sampling with careful genomospecies identification is needed for a solid conclusion.

2-Isopropylmalate Synthase↗

Alternate pathway for isoleucine biosynthesis in Escherichia coli.

A threonine dehydrataseless mutant of Escherichia coli, Crookes strain, was observed to grow on an acetate minimal medium without the usual requirement for isoleucine supplementation. Both the wild-type Crookes strain and a threonine auxotroph metabolized l-glutamate-1-(14)C to l-isoleucine-1-(14)C with no appreciable randomization, suggesting that a pathway for isoleucine formation from glutamate via beta-methylaspartate, beta-methyloxaloacetate, and alpha-ketobutyrate was possible in addition to the pathway from threonine and alpha-ketobutyrate. Crude cell-free extracts formed (14)C-beta-methylaspartate from (14)C-glutamate, and the conversion of beta-methylaspartate to alpha-ketobutyrate was also demonstrated, thus supporting the conclusion that glutamate can serve as a precursor of alpha-ketobutyrate (and isoleucine) without the necessary involvement of threonine as an intermediate.

Acetates↗

Involvement of threonine deaminase in repression of the isoleucine-valine and leucine pathways in Saccharomyces cerevisiae.

l-Threonine deaminase (l-threonine dehydratase [deaminating], EC 4.2.2.16) has been shown to be involved in the regulation of three of the enzymes of isoleucine-valine biosynthesis in yeast. Mutations affecting the affinity of the enzyme for isoleucine also affected the repression of acetohydroxyacid synthase, dihydroxyacid dehydrase, and reductoisomerase. The data indicate that isoleucine must be bound for effective repression of these enzymes to take place. In a strain with a nonsense mutation midway in liv 1, the gene for threonine deaminase, starvation for isoleucine or valine did not lead to derepression of the three enzymes; starvation for leucine did. The effect of the nonsense mutation is recessive; it is tentatively concluded, therefore, that intact threonine deaminase is required for derepression by two of the effectors for multivalent repression, but not by the third. A model is presented which proposes that a regulatory species of leu tRNA(leu) is the key intermediate for repression and that threonine deaminase is a positive element, regulating the available pool of charged leu tRNA by binding it.

Culture Media↗

Metabolic basis for the isoleucine, pantothenate or methionine requirement of ilvG strains of Salmonella typhimurium.

Salmonella typhimurium strain DU501, which was found to be deficient in acetohydroxy acid synthase II (AHAS II) and to possess elevated levels of transaminase B and biosynthetic threonine deaminase, required isoleucine, methionine, or pantothenate for growth. This strain accumulated alpha-ketobutyrate and, to a lesser extent, alpha-aminobutyrate. We found that alpha-ketobutyrate was a competitive substrate for ketopantoate hydroxymethyltransferase, the first enzyme in pantothenate biosynthesis. This competition with the normal substrate, alpha-ketoisovalerate, limited the supply of pantothenate, which resulted in a requirement for methionine. Evidence is presented to support the conclusion that the ambivalent requirement for either pantothenate or methionine is related to a decrease in succinyl coenzyme A, which is produced from pantothenate and which is an obligatory precursor of methionine biosynthesis. The autointoxification by endogenously produced alpha-ketobutyrate could be mimicked in wild-type S. typhimurium by exogenously supplied alpha-ketobutyrate or salicylate, a known inhibitor of pantothenate biosynthesis. The accumulation of alpha-ketobutyrate was initiated by the inability of the residual AHAS activity provided by AHAS I to efficiently remove the alpha-ketobutyrate produced by biosynthetic threonine deaminase. The accumulation of alpha-ketobutyrate was amplified by the action of transaminase B, which decreased the isoleucine pool by catalyzing the formation of alpha-keto-beta-methylvalerate and aminobutyrate from isoleucine and alpha-ketobutyrate; this resulted in release of threonine deaminase from end product inhibition and unbridled production of alpha-ketobutyrate. Isoleucine satisfied the auxotrophic requirement of the AHAS II-deficient strain by curtailing the activity of threonine deaminase. Additional lines of evidence based on genetic and physiological experiments are presented to support the basis for the autointoxification of strain DU501 as well as other nonpolarigenic ilvG mutant strains.

Acetolactate Synthase↗

Pseudoauxotrophy of Methanococcus voltae for acetate, leucine, and isoleucine.

Methanococcus voltae is a methanogenic bacterium which requires leucine, isoleucine, and acetate for growth. However, it also can synthesize these amino acids, and it is capable of low levels of autotrophic acetyl coenzyme A (acetyl-CoA) biosynthesis. When cells were grown in the presence of 14CO2, as well as in the presence of compounds required for growth, the alanine found in the cellular protein was radiolabeled. The percentages of radiolabel in the C-1, C-2, and C-3 positions of alanine were 64, 24, and 16%, respectively. The incorporation of radiolabel into the C-2 and C-3 positions of alanine demonstrated the autotrophic acetyl-CoA biosynthetic pathway in this bacterium. Additional evidence was obtained in cell extracts in which autotrophically synthesized acetyl-CoA was trapped into lactate. In these extracts, both CO and CH2O stimulated acetyl-CoA synthesis. 14CH2O was specifically incorporated into the C-3 of lactate. Cell extracts of M. voltae also contained low levels of CO dehydrogenase, 13 nmol min-1 mg of protein-1. These results further confirmed the presence of the autotrophic acetyl-CoA biosynthetic pathway in M. voltae. Likewise, 14CO2 and [U-14C]acetate were also incorporated into leucine and isoleucine during growth. During growth with [U-14C]leucine or [U-14C]isoleucine, the specific radioactivity of these amino acids in the culture medium declined, and the specific radioactivities of these amino acids recovered from the cellular protein were 32 to 40% lower than the initial specific radioactivities in the medium. Cell extracts of M. voltae also contained levels of isopropyl malate synthase, an enzyme that is specific to the leucine biosynthetic pathway, of 0.8 nmol min-1 mg of protein-1. Thus, M. voltae is capable of autotrophic CO2 fixation and leucine and isoleucine biosynthesis.

Acetates↗

Export of L-isoleucine from Corynebacterium glutamicum: a two-gene-encoded member of a new translocator family.

Bacteria possess amino acid export systems, and Corynebacterium glutamicum excretes L-isoleucine in a process dependent on the proton motive force. 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. In one such mutant, strong peptide sensitivity resulted from insertion into a gene designated brnF encoding a hydrophobic protein predicted to possess seven transmembrane spanning helices. brnE is located downstream of brnF and encodes a second hydrophobic protein with four putative membrane-spanning helices. A mutant deleted of both genes no longer exports L-isoleucine, whereas an overexpressing strain exports this amino acid at an increased rate. BrnF and BrnE together are also required for the export of L-leucine and L-valine. BrnFE is thus a two-component export permease specific for aliphatic hydrophobic amino acids. Upstream of brnFE and transcribed divergently is an Lrp-like regulatory gene required for active export. Searches for homologues of BrnFE show that this type of exporter is widespread in prokaryotes but lacking in eukaryotes and that both gene products which together comprise the members of a novel family, the LIV-E family, generally map together within a single operon. Comparisons of the BrnF and BrnE phylogenetic trees show that gene duplication events in the early bacterial lineage gave rise to multiple paralogues that have been retained in alpha-proteobacteria but not in other prokaryotes analyzed.

Amino Acid Transport Systems↗

Biochemical and genetic analysis of isoleucine and valine biosynthesis in Staphylococcus aureus.

After a prototrophic strain of Staphylococcus aureus had been exposed to diethyl sulfate, 28 isoleucine- and isoleucine-valine-dependent mutants (ilv mutants) were isolated. On the basis of auxanography, their ability to accumulate intermediates of isoleucine and valine biosynthesis, and intergeneric syntrophism with ilv mutants of Salmonella typhimurium, all mutants were placed into four groups, each of which corresponded to a presumed enzymatic deficiency, as follows: group A, deficient in l-threonine deaminase; group B, deficient in the condensing enzyme; group C, deficient in reductoisomerase; group D, deficient in alpha-beta-dihydroxy acid dehydrase. No mutants blocked in the terminal (transaminase) reactions were isolated. Transduction analyses (best-fit, ratio, and complementation tests) with the use of phage 83 established that the linear arrangement of the structural genes is identical with the order of participation of their enzymes in isoleucine and valine biosynthesis, and that these genes comprise a single linkage group which can exist on a single donor fragment during transduction.

Genetics↗

Biosynthesis of branched-chain amino acids in yeast: regulation of synthesis of the enzymes of isoleucine and valine biosynthesis.

Regulation of the levels of the five enzymes required for the biosynthesis of isoleucine and valine was studied in a Saccharomyces sp. When a mixture of isoleucine, valine, and leucine was added to the medium, the enzymes in the wild-type strain were repressed from about 30% (transaminase B) to about 90% (acetohydroxy acid synthetase) relative to the level in minimal medium-grown cells. Repression was also observed when threonine replaced isoleucine in the mixture but not when it replaced the other two amino acids. Significant derepression relative to the level in minimal-grown cells was not obtained by growing suitably blocked auxotrophs on medium containing limiting amounts of valine, isoleucine, or leucine.

Enzyme Repression↗