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 127 records · Page 7Linked to original sources
PubMed1966

Interference between leucine, isoleucine and valine during intestinal absorption.

1. The reciprocal interference between l-leucine, l-isoleucine and l-valine during absorption was studied in rats both in vivo and with an everted-sac preparation in vitro. 2. After feeding with the amino acids alone there was a considerable increase in their concentration in the intestinal lumen followed by a rapid disappearance, indicating efficient absorption. Absorption was reflected by a high concentration of the respective amino acids in the portal plasma. Isoleucine and valine inhibited the absorption of leucine, and leucine inhibited the absorption of isoleucine and valine. Inhibition of absorption by the interfering amino acid was generally partly overcome after 30-60min., probably through the absorption of the interfering amino acid. At that time the rise in the concentration of the amino acid in portal plasma began. 3. These results were confirmed by experiments in vitro: isoleucine and valine inhibited the absorption rate of leucine, and leucine that of isoleucine and valine. 4. Active absorption of amino acids was rapid at low concentrations and depressed at higher concentrations.

Amino Acids↗
PubMed1998

Iatrogenic isolated isoleucine deficiency as the cause of an acrodermatitis enteropathica-like syndrome.

We present two patients with a suspected inborn error of metabolism. A female newborn presented with dysmorphic features and convulsions. Metabolic screening suggested a defect in isoleucine degradation. Within 2 weeks after the introduction of an isoleucine-restricted diet, she developed a severe acrodermatitis enteropathica-like syndrome. The plasma level of isoleucine was low with a normal leucine/isoleucine ratio. The second patient, a female infant deficient in leucine as a result of a leucine-restricted diet, did not develop a dermatosis. Isoleucine is essential for normal growth and differentiation of keratinocytes and enterocytes. Deficiency of isoleucine, and not leucine or an imbalance in the leucine/isoleucine ratio, may result in an acrodermatitis enteropathica-like syndrome.

Acrodermatitis↗
PubMed2000

An investigation of the metabolism of isoleucine to active Amyl alcohol in Saccharomyces cerevisiae.

The metabolism of isoleucine to active amyl alcohol (2-methylbutanol) in yeast was examined by the use of (13)C nuclear magnetic resonance spectroscopy, combined gas chromatography-mass spectrometry, and a variety of mutants. From the identified metabolites a number of routes between isoleucine and active amyl alcohol seemed possible. All involved the initial decarboxylation of isoleucine to alpha-keto-beta-methylvalerate. The first, via branched chain alpha-ketoacid dehydrogenase to alpha-methylbutyryl-CoA, was eliminated because abolition of branched-chain alpha-ketoacid dehydrogenase in an lpd1 disruption mutant did not prevent the formation of active amyl alcohol. However, the lpd1 mutant still produced large amounts of alpha-methylbutyrate which initially seemed contradictory because it had been assumed that alpha-methylbutyrate was derived from alpha-methylbutyryl-CoA via acyl-CoA hydrolase. Subsequently it was observed that alpha-methylbutyrate arises from the non-enzymic oxidation of alpha-methylbutyraldehyde (the immediate decarboxylation product of alpha-keto-beta-methylvalerate). Mutant studies showed that one of the decarboxylases encoded by PDC1, PDC5, PDC6, YDL080c, or YDR380w must be present to allow yeast to utilize alpha-keto-beta-methylvalerate. Apparently, any one of this family of decarboxylases is sufficient to allow the catabolism of isoleucine to active amyl alcohol. This is the first demonstration of a role for the gene product of YDR380w, and it also shows that the decarboxylation steps for each alpha-keto acid in the catabolic pathways of leucine, valine, and isoleucine are accomplished in subtly different ways. In leucine catabolism, the enzyme encoded by YDL080c is solely responsible for the decarboxylation of alpha-ketoisocaproate, whereas in valine catabolism any one of the isozymes of pyruvate decarboxylase will decarboxylate alpha-ketoisovalerate.

Amino Acid Sequence↗
PubMed1996

Subchronic toxicity study of L-isoleucine in F344 rats.

A subchronic toxicity study with L-isoleucine was conducted using F344 rats. Groups of 10 rats of each sex were given diet containing 0, 1.25, 2.5, 5.0, or 8.0% L-isoleucine for 13 wk. No treatment-related effects were observed in terms of body weight change, food consumption or hematology. In both sexes given 8.0% L-isoleucine, increased or a tendency for increased urine volume and relative kidney weights were observed. Furthermore, the high-dose L-isoleucine treatment brought about an elevation of urinary pH and variations in serum electrolytes. However, histopathological alterations related to these changes were not observed in any organs of either sex. In conclusion, the present study demonstrated that L-isoleucine possessed minimal toxicity at dietary levels of 5.0% and 8.0%, while it did not exert any adverse affects at a dietary level of 2.5% or less.

Animals↗
PubMed1973

Synchronization of mitochondrial DNA synthesis in Chinese hamster cells (line CHO) deprived of isoleucine.

Mitochondrial DNA (mit-DNA) synthesis was compared in suspension cultures of Chinese hamster cells (line CHO) whose cell cycle events had been synchronized by isoleucine deprivation or mitotic selection. At hourly intervals during cell cycle progression, synchronized cells were exposed to tritiated thymidine ([(3)H]TdR), homogenized, and nuclei and mitochondria isolated by differential centrifugation. Mit-DNA and nuclear DNA were isolated and incorporation of radioisotope measured as counts per minute ([(3)H]TdR) per microgram DNA. Mit-DNA synthesis in cells synchronized by mitotic selection began after 4 h and continued for approximately 9 h. This time-course pattern resembled that of nuclear DNA synthesis. In contrast, mit-DNA synthesis in cells synchronized by isoleucine deprivation did not begin until 9-12 h after addition of isoleucine and virtually all [(3)H]TdR was incorporated during a 3-h interval. We have concluded from these results that mit-DNA synthesis is inhibited in CHO cells which are arrested in G(1) because of isoleucine deprivation and that addition of isoleucine stimulates synchronous synthesis of mit-DNA. We believe this method of synchronizing mit-DNA synthesis may be of value in studies of factors which regulate synthesis of mit-DNA.

Animals↗
PubMed1990

Optimal dietary substitution of racemic ketoanalogues for isoleucine in growing normal and uremic rats.

Dietary ketoanalogues (KAs) were shown to replace their essential amino acids with a 50% efficiency for valine and leucine. We determined the optimal concentration of the racemic KA of isoleucine (KMVA) in uremic and control rats: nutrition responses were compared between a diet containing optimal isoleucine concentration and diets containing various KMVA concentrations. Isomolar replacement of isoleucine produced anorexia, stunting, and poor nitrogen balance. Doubling KMVA partially improved these indices. Tripling KMVA lessened urea production and improved growth up to that obtained with the isoleucine diet in uremic but not in control rats (20% lower). A further KMVA increase produced no further benefit. Among plasma branched-chain amino acids, only alloisoleucine was affected; it increased with increasing KMVA concentration, being maximum after tripling KMVA. Racemic KMVA could replace isoleucine with a 35% efficiency but supported no growth acceleration in uremic rats and no maximal growth in control rats. Plasma alloisoleucine rose without adverse nutrition effects.

Amino Acids, Essential↗
PubMed1999

Differential and additive effects of the three conserved isoleucine residues in the promoter -10 binding region on Bacillus subtilis sigma(A) structure and function.

The promoter -10 binding region of the Bacillus subtilis sigma(A) factor forms an amphiphilic alpha-helix with three conserved isoleucines located at four-residue intervals. To investigate the structural and functional roles of the three isoleucine residues, we constructed a series of sigA mutants with single and double Ile-to-Ala substitutions on the hydrophobic face of this alpha-helix and isolated intragenic revertants with either same-site or second-site suppressor that partially restores the structural stability and transcription activity of the mutant sigma(A) factors. Our data show that the three conserved isoleucine residues (Ile-194, Ile-198, and Ile-202) are involved in the hydrophobic core packing of sigma(A); they affect differentially and additively the structure and function of sigma(A), with the central isoleucine residue (Ile-198) playing the most important role. By analogy with the crystal structure of a sigma(70) peptide, it is apparent that interdigital interactions exist between the three conserved isoleucine residues and certain hydrophobic amino acids in region 2. 1 of sigma(A). They include at least the van der Waals contacts between Ile-194 and both Leu-145 and Ile-149, between Ile-198 and both Ile-149 and Tyr-153, as well as between Ile-202 and Tyr-153. The same-site suppressors, Val-194 and Val-198, restore the structural stability and transcription activity of sigma(A) by repacking the hydrophobic core of sigma(A). The second-site suppressor (S291F) appears to be allele-specific, but it is not as effective as the same-site suppressors in restoring sigma(A) structure and function.

Amino Acid Sequence↗
PubMed2001

Tolerance of point substitution of methionine for isoleucine in hen egg white lysozyme.

X-ray structure determination of proteins by using the multiple-wavelength anomalous dispersion method targeting selenomethionine is now widely employed. Isoleucine was examined for the second choice of the substitution of methionine next to leucine. We performed a systematic mutational study of the substitutions of methionine for isoleucine. All mutated lysozymes were less stable than the wild-type by about 1 kcal/mol and it is suggested that this instability was caused by the change in residual hydrophobicity from isoleucine to methionine. The X-ray structures of all mutant lysozymes were very similar to that of the wild-type. In addition, both the accessible surface areas and the conformation of the side chain of methionine in all mutant lysozymes were similar to those of the side chain at the respective isoleucine in the wild-type. Therefore, it is suggested that the mutation from isoleucine to methionine in a protein can be considered as a "safe" substitution.

Amino Acid Substitution↗
PubMed1986

Isoleucine and valine oxidation following skeletal trauma in rats.

Nitrogen losses in the urine are derived from amino acid oxidation, and the increased loss of urinary nitrogen during stress indicates accelerated amino acid oxidation. This study compared isoleucine and valine oxidation by traumatized rats with that by pair-fed control rats. Seventy rats received bilateral hind limb fractures and were fed an oral liquid diet ad libitum, and 70 healthy rats were pair-fed with the trauma group. Daily food intake, body weight, and 24-hr urinary nitrogen were monitored for each animal, and isoleucine and valine oxidation were measured on days 1 through 7 postinjury using five rats from each group for each amino acid. Amino acid oxidation was determined from the percentage of dose appearing in the breath during 4 hours following a single injection of C-14 labeled amino acid. Anesthesia had a pronounced effect on all parameters on day 1, and its effects were dissipated by day 2. Skeletal trauma produced elevated urinary nitrogen losses that lasted for 5 days and peaked on day 3. Valine and isoleucine oxidation were increased for 5 days, and the peak increase occurred on day 3 post-trauma. These data show that isoleucine and valine oxidation parallel excessive urinary nitrogen excretion after skeletal trauma and that isoleucine and valine, like leucine, contribute to the increased urinary losses after trauma.

Animals↗
PubMed1972

Enzymes of the isoleucine-valine pathway in Acinetobacter.

Regulation of four of the enzymes required for isoleucine and valine biosynthesis in Acinetobacter was studied. A three- to fourfold derepression of acetohydroxyacid synthetase was routinely observed in two different wild-type strains when grown in minimal medium relative to cells grown in minimal medium supplemented with leucine, valine, and isoleucine. A similar degree of synthetase derepression was observed in appropriately grown isoleucine or leucine auxotrophs. No significant derepression of threonine deaminase or transaminase B occurred in either wild-type or mutant cells grown under a variety of conditions. Three amino acid analogues were tested with wild-type cells; except for a two- to threefold derepression of dihydroxyacid dehydrase when high concentrations of aminobutyric acid were added to the medium, essentially the same results were obtained. Experiments showed that threonine deaminase is subject to feedback inhibition by isoleucine and that valine reverses this inhibition. Cooperative effects in threonine deaminase were demonstrated with crude extracts. The data indicate that the synthesis of isoleucine and valine in Acinetobacter is regulated by repression control of acetohydroxyacid synthetase and feedback inhibition of threonine deaminase and acetohydroxyacid synthetase.

Alcaligenes↗
PubMed1974

Amino acid biosynthesis in the spirochete Leptospira: evidence for a novel pathway of isoleucine biosynthesis.

Radioactive carbon dioxide was incubated with growing cells of Leptospira interrogans serotypes semaranga and tarassovi, and the specific activities and distribution of the label within the cellular amino acids were determined. The origins of the carbon skeletons of all the acid-stable amino acids except isoleucine were found to be consistent with known biosynthetic pathways for these amino acids. Experiments using radioactive carbon dioxide and other tracers indicated that most of the isoleucine was synthesized by a pathway not involving threonine. The origin of the carbon skeleton of isoleucine consisted of two residues of pyruvate (carbons 2 and 3) and acetate of acetyl-coenzyme A by this pathway. Isotope competition studies indicated that the pathway was regulated by isoleucine. The results are discussed in relation to two proposed pathways of isoleucine biosynthesis involving citramalate as an intermediate.

Amino Acids↗
PubMed1974

Multiplicity of isoleucine, leucine, and valine transport systems in Escherichia coli K-12.

The kinetics of isoleucine, leucine, and valine transport in Escherichia coli K-12 has been analyzed as a function of substrate concentration. Such analysis permits an operational definition of several transport systems having different affinities for their substrates. The identification of these transport systems was made possible by experiments on specific mutants whose isolation and characterization is described elsewhere. The transport process with highest affinity was called the "very-high-affinity"process. Isoleucine, leucine, and valine are substrates of this transport process and their apparent K(m) values are either 10(-8), 2 x 10(-8), or 10(-7) M, respectively. Methionine, threonine, and alanine inhibit this transport process, probably because they are also substrates. The very-high-affinity transport process is absent when bacteria are grown in the presence of methionine, and this is due to a specific repression. Methionine and alanine were also found to affect the pool size of isoleucine and valine. Another transport process is the "high-affinity" process. Isoleucine, leucine, and valine are substrates of this transport process, and their apparent K(m) value is 2 x 10(-6) M for all three. Methionine and alanine cause very little or no inhibition, whereas threonine appears to be a weak inhibitor. Several structural analogues of the branched-chain amino acids inhibit the very-high-affinity or the high-affinity transport process in a specific way, and this confirms their existence as two separate entities. Three different "low-affinity" transport processes, each specific for either isoleucine or leucine or valine, show apparent K(m) values of 0.5 x 10(-4) M. These transport processes show a very high substrate specificity since no inhibitor was found among other amino acids or among many branched-chain amino acid precursors or analogues tried. The evolutionary significance of the observed redundancy of transport systems is discussed.

Alanine↗
PubMed1974

Role of the leu-3 cistron in the regulation of the synthesis of isoleucine and valine biosynthetic enzymes of Neurospora.

The production by Neurospora of the enzymes of isoleucine and valine synthesis in response to specific end product-derived signals depends upon the presence of an effective leu-3 regulatory product and its effector alpha-isopropylmalate (alpha-IPM). In leu-3(+) strains, threonine deaminase production is repressed as a function of available isoleucine, acetohydroxy acid synthetase as a function of valine, and the isomeroreductase and dihydroxy acid dehydratase as a function of isoleucine and leucine. In the absence of an effective leu-3 regulatory product, alpha-isopropylmalate, or both, the production of isoleucine and valine biosynthetic enzymes is fixed at or near fully repressed levels even under conditions of severe end product limitation. Thus, in addition to its involvement in the regulation of expression of the three structural genes of leucine synthesis, the leu-3 alpha-IPM regulatory product is necessary for full expression of at least four genes specifying the structure of the enzymes of isoleucine and valine synthesis. It is suggested that the leu-3 alpha-IPM regulatory element may facilitate transcription of the genetically dispersed cistrons either by imposing specificity on ribonucleic acid polymerase for structurally similar promoters adjacent to each of the cistrons or by "opening" promoters after interaction with nearly identical stretches of deoxyribonucleic acid near each of the structural genes.

Alcohol Oxidoreductases↗
PubMed1976

Threonine deaminase from a nonsense mutant of Escherichia coli requiring isoleucine or pyridoxine: evidence for half-of-the-sites reactivity.

The mutant IP7 of Escherichia coli B requires isoleucine or pyridoxine for growth as a consequence of a mutation in the gene coding for biosynthetic threonine deaminase. The mutation of IP7 was shown to be of the nonsense type by the following data: (1) reversion to isoleucine prototrophy involves the formation of external suppression at a high frequency, as shown by transduction experiments; and (ii) the isoleucine requirement is suppressed by lysogenization with a phage carrying the amber suppressor su-3. Cell extracts of the mutant strain contain a low activity of threonine deaminase. The possibility that this activity is biodegradative was ruled out by kinetic experiments. The mutant threonine deaminase was purified to homogeneity by conventional procedures. The enzyme is a dimer of identical subunits of an approximate molecular weight of 43,000 (Grimminger and Feldner, 1974), whereas the wild-type enzyme is a tetramer of 50,000-dalton subunits (Calhoun et al., 1973; Grimminger et al., 1973). The mutant enzyme is not inhibited by isoleucine and does not bind isoleucine, as shown by equilibrium dialysis experiments. Pyridoxal phosphate enhances the maximum catalytic activity of the mutant enzyme by a factor of five, whereas the wild-type enzyme is not affected. In wild-type and mutant threonine deaminase the ratio of protein subunits and bound pyridoxal phosphate is 2:1. The activation of threonine deaminase from strain IP7 is due to a second coenzyme binding site, as shown by (i) spectrophotometric titration of the enzyme with pyridoxal phosphate and by (ii) measurement the pyridoxal phosphate content of the enzyme after sodium borohydride reduction of the protein. The observation of one pyridoxal phosphate binding site per peptide dimer in the wild-type enzyme and of two binding sites per dimer in the mutant strongly suggests that one of the potential sites in the wild-type enzyme is masked by allosteric effects. The factors responsible for the half-of-the-sites reactivity of the coenzyme sites appear to be nonoperative in the mutant protein.

Binding Sites↗
PubMed1986

Acetohydroxy acid synthase I, a required enzyme for isoleucine and valine biosynthesis in Escherichia coli K-12 during growth on acetate as the sole carbon source.

Escherichia coli K-12 has two acetohydroxy acid synthase (AHAS) isozymes (AHAS I and AHAS III). Both of these isozymes catalyze the synthesis of alpha-aceto-alpha-hydroxybutyrate and alpha-acetolactate, which are key intermediates of the isoleucine-valine biosynthetic pathway. Strains lacking either isozyme but not both activities have been previously shown to grow well in minimal media in the absence of isoleucine and valine on any of several commonly used carbon sources (e.g., glucose or succinate). We report the characterization of mutants that were unable to grow on either acetate or oleate as a sole carbon source due to a defect in isoleucine-valine biosynthesis. The defect in isoleucine-valine biosynthesis was expressed only on these carbon sources and was due to the loss of AHAS I activity, resulting from lesions in the ilvBN operon. Previously identified ilvBN mutant strains also failed to grow on acetate or oleate minimal media. Our results indicated that AHAS I is an essential enzyme for isoleucine and valine biosynthesis when E. coli K-12 is grown on acetate or oleate as the sole carbon source. AHAS III was expressed during growth on acetate or oleate but was somehow unable to produce sufficient amounts of alpha-aceto-alpha-hydroxybutyrate and alpha-acetolactate to allow growth.

Acetates↗
PubMed1999

Cold shock response of Bacillus subtilis: isoleucine-dependent switch in the fatty acid branching pattern for membrane adaptation to low temperatures.

Bacillus subtilis has developed sophisticated mechanisms to withstand fluctuations in temperature. Membrane fatty acids are the major determinants for a sufficiently fluid membrane state to ensure the membrane's function at all temperatures. The fatty acid profile of B. subtilis is characterized by a high content of branched fatty acids irrespective of the growth medium. Here, we report on the importance of isoleucine for B. subtilis to survive cold shock from 37 to 15 degrees C. Cold shock experiments with strain JH642 revealed a cold-protective function for all intermediates of anteiso-branched fatty acid biosynthesis. Metabolites related to iso-branched or straight-chain fatty acid biosynthesis were not protective. Fatty acid profiles of different B. subtilis wild-type strains proved the altered branching pattern by an increase in the anteiso-branched fatty acid content and a concomitant decrease of iso-branched species during cold shock. There were no significant changes in the fatty acid saturation or acyl chain length. The cold-sensitive phenotype of isoleucine-deficient strains in the absence of isoleucine correlated with their inability to synthesize more anteiso-branched fatty acids, as shown by the fatty acid profile. The switch to a fatty acid profile dominated by anteiso-C(15:0) and C(17:0) at low temperatures and the cold-sensitive phenotype of isoleucine-deficient strains in the absence of isoleucine focused our attention on the critical role of anteiso-branched fatty acids in the growth of B. subtilis in the cold.

Adaptation, Physiological↗
PubMed1961

Role of valine and isoleucine as regulators of actinomycin peptide formation by Streptomyces chrysomallus.

Katz, Edward (Rutgers, The State University, New Brunswick, N. J.), Clarence R. Waldron, and Mary Lou Meloni. Role of valine and isoleucine as regulators of actinomycin peptide formation by Streptomyces chrysomallus. J. Bacteriol. 82:600-608. 1961-d-Valine is an effective inhibitor of actinomycin synthesis by Streptomyces chrysomallus; l-valine stimulates actinomycin production and reverses the inhibition due to the d-enantiomorph. The incorporation of l-valine into the medium results, particularly, in a marked increase in actinomycin IV formation. In studies with various isoleucine isomers it was shown that l-isoleucine enhances actinomycin VII production; the principal effect of d-alloisoleucine and, especially, d-isoleucine, is to bring about synthesis of two new actinomycins which contain N-methylisoleucine. Both l- and d-threonine were observed to have an effect similar to that obtained with l-isoleucine. An interpretation of these findings has been discussed.

Amino Acids↗
PubMed1979

The effect of L-alpha-amino-n-butyric acid on growth and production of extracellular isoleucine and valine by Eubacterium ruminantium and a related rumen isolate.

Two anaerobic rumen bacteria, Eubacterium ruminantium and a closely related isolate, were studied to determine the effect of the valine antimetabolite alpha-aminobutyric acid on growth and production of extracellular isoleucine and valine in an amino acid free medium. In the absence of alpha-aminobutyrate, these organisms actively excreted valine during growth (90-195 microgram/mL) but only accumulated limited concentrations of isoleucine (3-7 microgram/mL) in the culture broth. Growth of both organisms was reduced in the presence of 0.5-1.5% alpha-aminobutyrate but this inhibition was largely overcome by the use of preadapted inoculum. Metabolism of alpha-aminobutyrate was also increased using preadapted inoculum. During growth in the presence of 0.5-1.5% alpha-aminobutyrate, both organisms accumulated high concentrations of isoleucine (100-225 microgram/mL) while the normal accumulation of valine was unaffected. alpha-Ketobutyrate, a product of alpha-aminobutyrate metabolism, also stimulated isoleucine excretion by these organisms. The results are discussed in relation to the regulation of the biosynthetic pathways of isoleucine and valine in these rumen anaerobes and the potential significance of this amino acid excretion in ruminant nutrition.

Adaptation, Physiological↗