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At least 199 records · Page 11Linked to original sources
PubMed1994

Transport of 2-aminoisobutyric acid in cultured endothelial cells.

Conflicting reports exist concerning the presence of a Na(+)-coupled amino acid transport system in cultured endothelial cells. We have employed a non-metabolizable analog, 2-aminoisobutyric acid (AIB), to investigate the activity of Na(+)-dependent amino acid transport in cultured human umbilical vein endothelial cells (HUVEC). We found a pronounced saturable, Na(+)-dependent component of AIB uptake in 'fresh' (non-starved) HUVEC. The Na(+)-dependent component accounted for 78% of total AIB uptake with a high sensitivity to external Na+. The accumulation of AIB was inhibited by ouabain preincubation, consistent with the energetics of Na(+)-coupled transport. Amiloride, an epithelial Na+ channel blocker, also inhibited AIB transport at high concentration. The results strongly support the presence of a Na(+)-coupled transport system of amino acid in HUVEC.

Amiloride↗
PubMed1985

Effects of dexamethasone on the blood-brain distribution of albumin and alpha-aminoisobutyric acid in vasogenic cerebral edema.

The effects of dexamethasone (Dex) on the blood-brain distribution of 14C-alpha-aminoisobutyric acid (AIB) and 125I-albumin (RISA) was studied in the rat freeze-lesion model of cerebral edema. Untreated and Dex-treated rats were studied by intravenously administering either AIB or RISA immediately after or one day after localized cortical freezing. The AIB experiments were terminated after 10 min; the RISA experiments were terminated after 30 min or 4 hr. Local tissue distribution of AIB and RISA was assessed by quantitative autoradiography. The distribution of both RISA and AIB within the lesion was unaffected by Dex. In the tissue around the lesion, Dex did not alter the distribution of AIB in the 10 min experiments or of RISA in the 30 min experiments. Dex did, however, diminish the movement of RISA into the adjacent tissue during the 4-hr experiments. The intralesional AIB and RISA distribution data plus the perilesional 10-min AIB and 30-min RISA distribution data indicate that Dex does not act by reducing the flow of solutes and water across damaged or leaky vessels in and around the lesion. The 4-hr RISA data suggests that Dex alters the structure of the extracellular space in the tissue around the lesion (especially in the white matter) and thereby increases the resistance of the interstitium to the flow of solutes and fluid from the lesion into the adjacent tissue.

Aminoisobutyric Acids↗
PubMed1991

Conformational preferences of oligopeptides rich in alpha-aminoisobutyric acid. I. Observation of a 3(10)/alpha-helical transition upon sequence permutation.

The solution conformation of peptides rich in the alpha, alpha-dialkylated amino acid Aib has proven to be a subtle problem, not because of helix/coil transitions, but rather because of alpha-helical/3(10)-helical competition. A special series of peptides containing 75% Aib has been synthesized that feature identical amino acid composition but differing sequences; they are sequence permutation isomers. Nuclear magnetic resonance hydrogen-bonding studies reveal that there is a sequence permutation induced transition between the two alternative helical forms within this set. The implications for the design and conformational prediction of helical Aib-rich peptides are discussed.

Amino Acid Sequence↗
PubMed1992

Conformational preferences of oligopeptides rich in alpha-aminoisobutyric acid. II. A model for the 3(10)/alpha-helix transition with composition and sequence sensitivity.

The analysis of the factors that control the helical folding of Aib-rich peptides is extended to include sensitivity to sequence patterns, and in particular the presence of contiguous non-Aib alpha-mono-alkylated residues. The distinct hydrogen-bonding network of the 3(10)-helix, as contrasted with that of the competing alpha-helical structure, is explicitly incorporated into a theoretical model for the 3(10)-helix/alpha-helix equilibrium constant for a given peptide. Finite length effects and the "extra" intrahelical hydrogen bond of the 3(10) form are expressed naturally as a result of this loop analysis. This semiempirical model captures all the established features of existing empirical rules for helical conformational transitions in Aib-rich sequences, as well as the recently detected helical transition induced solely by sequence permutation.

Amino Acid Sequence↗
PubMed1990

Apolar peptide models for conformational heterogeneity, hydration, and packing of polypeptide helices: crystal structure of hepta- and octapeptides containing alpha-aminoisobutyric acid.

The crystal structures of two helical peptides Boc-Val-Ala-Leu-Aib-Val-ala-Leu-OMe (VALU-7) and Boc-Val-Ala-Leu-Aib-Val-Ala-Leu-Aib-OMe (VALU-8) have been determined to a resolution of 1.0 and 0.9 A, respectively. Both the seven and eight residue peptides crystallize with two conformers per asymmetric unit. The VALU-8 conformers are completely helical and differ only at the C-terminus by a sign reversal of the phi, psi angles of the last residue. One of the VALU-7 conformers occurs as a normal alpha-helix, whereas in the other, the N(7)--O(3) alpha-type hydrogen bond is ruptured by the entry of a water molecule (W) into the helix, which in turn makes hydrogen bonds N(7)...W = 2.97 A and W...O(3) = 2.77 A. The other side of the water molecule is surrounded by a hydrophobic pocket. These two conformers give a static representation of a step in a possible helix unwinding or folding process. In the VALU-8 crystal the helices aggregate in a parallel mode, whereas the aggregation is anti-parallel in the VALU-7 crystal. The crystal parameters are VALU-7, P2(1), a = 10.203 (3) A, b = 19.744 (6) A, c = 22.561 (6) A, beta = 96.76 degrees, Z = 4, C38H69N7O10.0.5H2O, R = 6.65% for 3674 reflections observed greater than 3 sigma (F); and VALU-8, P2(1), a = 10.593 (4) A, b = 27.57 (6) A, c = 17.745 (5) A, beta = 95.76 (3) degrees, Z = 4, C42H76N8O11.0.25 CH3OH, R = 6.63% for 4701 reflections observed greater than 3 sigma (F).

Amino Acid Sequence↗
PubMedDate not supplied

Effects of protein-calorie malnutrition on transplacental kinetics of aminoisobutyric acid in rats.

In order to find out if inefficient transport of amino acids contributes to a decrease in fetal weight during maternal malnutrition, we injected [14C]- and [3H]-labelled aminoisobutyric acid (AIB), respectively, in the mother and its fetuses and determined its transplacental kinetics on day 20 of gestation in rats fed a 21 per cent (control) or a low (5 per cent) protein diet. Rats fed a low protein diet consumed significantly less food than did the rats fed a control diet and thus suffered from protein-calorie malnutrition. A low protein diet led to a significant (P less than 0.05) decrease in maternal and fetal volume of distribution of AIB, a decrease in the clearance of AIB from the mother to the fetus and an increase in the time required for the fetal plasma AIB concentration following maternal injection to exceed the maternal plasma AIB concentration. The clearance of AIB from the fetus into the mother or to outside (e.g. amniotic fluid) was not altered by protein deficiency. It is concluded that a decrease in the efficiency of the placenta to deliver amino acids to the fetus may be a contributing factor in fetal growth retardation during maternal protein malnutrition.

Aminoisobutyric Acids↗
PubMed1981

1H N.M.R. studies of protected alpha-aminoisobutyric acid containing peptides. Chemical shift nonequivalence of benzyloxycarbonyl methylene protons.

The benzylic methylene protons in a large number of benzyloxycarbonyl alpha-aminoisobutyric acid (Z-Aib) containing peptides, show chemical shift nonequivalence. The magnitude of the geminal nonequivalence is correlated with the involvement of the urethane carbonyl group, in an intramolecular hydrogen bond. Studies of the model compounds Z-Aib-Aib-Ala-NHMe, and Z-Aib-Aib-Aib-Pro-OMe clearly establish the presence of intramolecular hydrogen bonds, involving the urethane CO group. In both compounds marked anisochrony of the benzylic methylene protons is demonstrated. In Z-Aib-Aib-Pro-OMe, where a 4 leads to 1 hydrogen bonded beta-turn is not possible, the benzylic-CH2-protons appear as a singlet in CDCl3 and have a very small chemical shift difference in (CD3)2SO. The observation of such nonequivalence is of value in establishing whether the amino terminal Aib-Pro beta-turn is retained in large peptide-fragments of alamethicin.

Aminoisobutyric Acids↗
PubMed1985

Rate equations and kinetics of uptake of alpha-aminoisobutyric acid and gamma-aminobutyric acid by mouse cerebrum slices incubated in media containing L(+)-lactate or a mixture of succinate, L-malate, and pyruvate as the energy source.

Influx of alpha-aminoisobutyric acid (AIB) and gamma-aminobutyric acid (GABA) by mouse cerebrum slices incubated with L-lactate or a mixture of succinate, L-malate, and pyruvate (SMP) as the energy source follows the phenomenological rate equation for influx from pyruvate and glucose media: v = Vmax/(1 + Kt/S) + kuS, where v is rate and S is concentration of amino acid. There are two kinetically distinct, parallel components for concentrative uptake, one saturable, and one unsaturable. Rates are less with lactate than with pyruvate and still less with SMP (only GABA was studied), disproving the hypotheses that lower rates with pyruvate compared to glucose are due to an abnormal redox state in the tissue or to a Krebs cycle unbalanced by input at only one point. The carriers for AIB and GABA are qualitatively different. In lactate medium the capacity of each AIB carrier is unchanged but its affinity is reduced to one-third. In lactate and SMP media, the capacity of the saturable GABA carrier is diminished although its affinity is increased. Rates from these media with added glucose or a glucose analog confirm that amino acid and glucose fluxes are not coupled.

Aminoisobutyric Acids↗
PubMed1988

Insulin-stimulated alpha-(methyl)aminoisobutyric acid uptake in skeletal muscle. Evidence for a short-term activation of uptake independent of Na+ electrochemical gradient and protein synthesis.

1. The present study was designed to explore the mechanisms by which insulin stimulates system A of amino acid transport in extensor digitorum longus (EDL) muscles, by using a system A analogue, alpha-(methyl)aminoisobutyric acid (MeAIB). 2. Insulin stimulation of MeAIB uptake was noted after only 30 min of incubation and was maximal at 60 min. Kinetics of the insulin effect on MeAIB uptake were characterized by an increased Vmax. without modification of Km for MeAIB. 3. Incubation of EDL muscles with cycloheximide for 90 min did not modify MeAIB uptake in either the presence or the absence of insulin, indicating the independence of insulin action from protein synthesis de novo. Incubations for 180 min with cycloheximide caused a decrease in basal MeAIB uptake; however, the percentage stimulation of amino acid transport by insulin was unaltered. Basal MeAIB uptake was increased by incubation for 180 min, but under these conditions no change in the percentage effect of insulin was found. 4. Ouabain, gramicidin D, or both, markedly decreased basal MeAIB uptake by EDL muscle, but the percentage effect of insulin was unaltered. 5. We conclude that insulin action on amino acid transport through system A in muscle is rapid, is characterized by an increased Vmax., and is independent of protein synthesis de novo and the Na+ electrochemical gradient. Our data are compatible with insulin acting directly on the system A transporter.

Aminoisobutyric Acids↗
PubMed1986

Altered excretion of modified nucleosides and beta-aminoisobutyric acid in subjects with acquired immunodeficiency syndrome or at risk for acquired immunodeficiency syndrome.

Urinary excretion of modified nucleosides and beta-aminoisobutyric acid, subsequently referred to as markers, was determined in populations of patients with acquired immunodeficiency syndrome (AIDS) or at risk for development of AIDS. Our results show that asymptomatic adult male homosexuals excreted elevated amounts of markers as compared to male heterosexuals. This aberrant excretion was more pronounced in asymptomatic adult male homosexuals with antibodies to HTLV-III. Significantly greater excretion of 1-methylinosine, N4-acetylcytidine, and N2-methylguanosine was observed in asymptomatic adult male homosexuals with antibodies to HTLV-III than in asymptomatic male homosexuals without antibodies to HTLV-III. Increased amounts of markers were also excreted by subjects with the generalized or chronic lymphadenopathy syndrome, AIDS related complex (ARC), or AIDS. In these subjects, the most pronounced differences between groups were between subjects with chronic lymphadenopathy syndrome and those with ARC; subjects with ARC excreted greater amounts of seven of the ten urinary markers. There were few differences between subjects with ARC and those with AIDS, Kaposi's sarcoma, or AIDS with opportunistic infections. This observation may be useful for identifying subjects who are at risk of developing AIDS. A prospective study to test this hypothesis is under way.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Helix-inducing alpha-aminoisobutyric acid in opioid mimetic deltorphin C analogues.

The achiral symmetric alpha-aminoisobutyric acid (Aib) replaced the critical N-terminal residues of the amphibian skin opioid deltorphin C (H-Tyr-D-Ala-Phe-Asp-Val-Val-Gly-NH2) without detriment to the physicochemical requirements for delta opioid receptor recognition. Substitutions by the alpha, alpha-dialkyl amino acid in place of D-Ala2 or Phe3, or both, exhibited high delta receptor affinity (Ki delta = 0.12-3.6 nM) and 5-9-fold greater selectivity (Ki mu/Ki delta = 5000-8500) than the parent compound. This is the first definitive demonstration that the D-chirality of alanine and the aromaticity of phenylalanine are replaceable by an achiral alpha, alpha-dialkylated residue without detrimental effects on ligand binding. Incorporation of the mono-alpha-alkyl amino acid L- or D-Ala at the third position also produced highly selective delta ligands (Ki mu/Ki delta = 2000-3500), albeit with reduced delta affinities (Ki delta = 6-15 nM). Replacement of the anionic residue Asp4 by Aib yielded an opioid peptide that fit two-site binding models for the delta receptor (eta = 0.763; P < 0.0001) and displayed dual high affinity for both delta and mu receptors, emphasizing the repulsive effect by a negative charge at mu receptor sites and the insignificance of Asp for delta affinity. Molecular dynamics conformation analyses suggested that Aib residues caused distinct changes in deltorphin C secondary structure when substituted for D-Ala2, Asp4, and simultaneously D-Ala2 and Phe3 but not when substituted for Phe3. These conformational changes might be critical factors for the proper orientation of reactive constituents of residues in the N-terminal region of deltorphin C. Disparities between binding data and functional bioassays of [Aib3] indicated that Phe3 was required for bioactivity in mouse vas deferens but not for interaction with delta opioid receptors in rat brain membranes.

Amino Acid Sequence↗
PubMed1998

A study of the effect of theophylline on the anti-inflammatory potency of dexamethasone using alpha-aminoisobutyric acid uptake in rat skin fibroblasts: a possible mechanism through the glucocorticoid receptor.

The action of theophylline on the uptake of alpha-aminoisobutyric acid (AIB; an indicator of anti-inflammatory potency) stimulated by the glucocorticoid, dexamethasone, in cultured rat fibroblast monolayers was evaluated. Theophylline alone (0.1 m m) did not show significant activity (3314+/-27 cpm) compared with the baseline level (3186+/-130 cpm), but in the presence of 10 n m dexamethasone the stimulation of AIB uptake was increased to 5263+/-100 cpm, approximately to the same extent as with 100 n m dexamethasone alone (5397+/-28 cpm). Activation of glucocorticoid-receptor complexes in rat fibroblast cytosol was studied by assessing the extent of their binding to DNA-cellulose. Activated and non-activated forms of glucocorticoid-receptor complexes were analysed by DEAE-Sephadex chromatography. Theophylline (1 m m) was found to have a direct effect (0 degrees C), similar to that of heat (25 degrees C) on DNA-cellulose binding, that is approximately 64.5% and 68.7%, respectively, thus indicating that theophylline promotes activation of glucocorticoid receptors at low temperature. The effect of theophylline on the stimulation of AIB uptake by dexamethasone when considered in the light of its activation of GR receptors in the fibroblast cytosol indicates that this effect may be mediated by GR activation.

Aminoisobutyric Acids↗
PubMed1972

Alpha-aminoisobutyric acid transport in human leukemic lymphocytes: in vitro characteristics and inhibition by cortisol and cycloheximide.

We have studied the transport of alpha-aminoisobutyric acid (AIB)-3-(14)C and its response to cortisol and cycloheximide in vitro in blood lymphocytes from untreated patients with chronic lymphocytic leukemia. The accumulation of AIB-3-(14)C increased in a linear fashion for 60 min, and reached an apparent steady state in 120 min. The initial rate of AIB accumulation (V(o)) varied from 1.1 to 10.2 mumoles/kg cell H(2)O per min in cells from 16 different patients; however, V(o) was reproducible in cells from five of six patients which were studied repeatedly over 1-9 months, and correlated positively with the lymphocyte count (r = 0.51, P = < 0.01). Virtually total inhibition of protein synthesis with cycloheximide was found to decrease the accumulation of AIB in cells from four patients which had high rates of AIB transport, but had no effect on transport in cells from four patients which accumulated AIB more slowly. These results indicate that active transport depends, in part, upon the presence of labile protein with a turnover rate which varies among different cell populations. Treatment with 10 muM cortisol for 240 min in vitro reduced the initial rate of AIB-3-(14)C accumulation (V(o)) by 43.4+/-4.1% (SE) (range, 9-66%) in cells from 16 patients. The degree of inhibition did not vary appreciably over a 9 month period in four of five patients. The effect of cortisol was proportional to its starting concentration, and developed at low concentrations (0.1-1.0 muM). Cortisol appears to decrease AIB accumulation by inhibiting active uptake, since it neither enhanced the exodus of AIB, nor inhibited apparently nonsaturable transport. Inhibition was noncompetitive in type, suggesting that cortisol decreases the total capacity of the active transport mechanism.Cortisol inhibited AIB transport indirectly by a process which involved de novo protein synthesis, since inhibition (a) appeared only after 60 min of treatment, (b) was present in treated cells which were subsequently incubated for 60 min in cortisol-free medium, and (c) failed to develop during simultaneous blockade of protein synthesis with cycloheximide, even when cycloheximide itself did not decrease AIB transport.

Aminoisobutyric Acids↗