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At least 19 recordsLinked to original sources
PubMed2000

Preparation and characterization of acrylic hydrogels neutralized by basic amino acids.

Basic amino acids were used as neutralizers in the gellation of Eudispert as an acrylic hydrogel. Arginine and lysine successfully neutralized Eudispert, as did sodium hydroxide, and formed hydrogels. A gentle rise of pH was observed as the dosage of the base increased when arginine and lysine were used, in contrast to the sharp rise of pH observed when sodium hydroxide was used. The rank of viscosity of the prepared hydrogels was as follows: lysine > arginine > NaOH. The release rate of model drugs (salicylic acid, theophylline, and bovine insulin) from the prepared hydrogels ranked as follows: NaOH>lysine>arginine, the sustained-release profile being observed with arginine. The rate of diffusion of the model drug from the hydrogel was inversely proportional to the molecular weight of the cationized neutralizer used. It is concluded that the strategy of neutralization of acidic polymers by basic amino acids has advantage with the respect to both the sustained-release characteristics of the gel and the biocompatibility of the basic amino acids themselves.

Amino Acids↗
PubMed1982

Electrophysiological analysis of rat renal sugar and amino acid transport. IV. Basic amino acids.

Electrophysiological techniques were used to study the transport of the basic amino acids L-arginine, L-lysine and L-ornithine in rat kidney proximal tubule in vivo. Tubular cells were punctured with microelectrodes and the response of the cell membrane potential to sudden applications of the amino acids was measured. In the presence of physiological Na+ concentrations luminal perfusion with millimolar concentrations of basic amino acids depolarized the tubular cells in a concentration dependent fashion by up to 15 mV, while in the absence of Na+ no significant potential changes were observed. These observations indicate that the basic amino acids are taken up into the cell across the brushborder in coupling with Na+ ions in a similar way as neutral and acidic amino acids, and that simple conductive pathways for uncoupled flow of the basic amino acids do either not exist or are quantitatively negligible in the brushborder. From kinetic measurements and competition experiments it was concluded that all basic amino acids are transported by the same transport system, which however does not accept acidic or neutral amino acids (with the possible exception of L-cystine). Perfusion of the peritubular capillaries with millimolar concentrations of basic amino acids depolarized the cells only by approximately 1 mV, both in the presence and absence of Na+. This observation may indicate that a passive uncoupled transport pathway for basic amino acids is present in the peritubular cell membrane to allow exit from cell to interstitial space, if the intracellular concentration rises high enough to overcome the cell membrane potential.

Amino Acids↗
PubMed1979

The dark respiration of Anacystis nidulans. Production of HCN from histidine and oxidation of basic amino acids.

The basic amino acids, L-arginine, L-lysine, LO-irnithine, and to a lesser extent L-histidine, strongly stimulate the O2 uptake of cell suspensions of the blue-green alga or cyanobacterium anacystis nidulans. In the case of L-histidine, the extra O2 consumption is associated with the formation in vivo of small amounts of HCN, particularly in an atmosphere of O2. The enzyme responsible for both the stimulated O2 uptake with the basic amino acids and the formation of HCN from histidine has been isolated and identified as an L-amino acid oxidase specific for the basic amino acids. The purification (15 000-fold) of this enzyme is described. The isolated enzyme is inhibited by o-phenanthroline, which has a similar inhibitory effect on the O2 uptake of cell suspensions with (and without) added amino acids. The basic amino acid oxidase, which is not inhibited by HCN, can be regarded as an 'alternate' oxidase in A. nidulans. An oxidase sensitive to HCN is apparently also operative. At high concentrations of lysine or arginine added HCN can almost double the initial rate of O2 consumption of cell suspensions. This can be attributed to the inhibition of catalase by HCN. At low concentrations of the amino acids, and with more prolonged incubation time, HCN becomes inhibitory. One interpretation could be that the HCN-sensitive terminal oxidase is also involved in the extra O2 uptake elicited by the basic amino acids, but other interpretations are possible. The extra O2 uptake elicited by histidine is almost completely inhibited by HCN, which is consistent with the finding that histidine is a relatively poor substrate for the basic amino acid oxidase.

Amino Acid Oxidoreductases↗
PubMed1995

Sodium-independent currents of opposite polarity evoked by neutral and cationic amino acids in neutral and basic amino acid transporter cRNA-injected oocytes.

To elucidate the electrical events associated with the movement of amino acids by the neutral and basic amino acid transporter (NBAT)-encoded protein (Yan, N., Mosckovitz, R., Gerber, L.D., Mathew, S., Murty, V.V. V.S., Tate, S.S., and Udenfriend, S. (1994) Proc. Natl. Acad. Sci. USA 91, 7548-7552), we have investigated the membrane potential and current changes associated with the increased transport of amino acids across the cell membrane of NBAT cRNA-injected Xenopus laevis oocytes. Superfusion of 0.05 mM L-phenylalanine, in current-clamped NBAT-injected oocytes, caused a hyperpolarization (8.5 +/- 0.9 mV), but superfusion of L-arginine caused a depolarization (18.3 +/- 1.3 mV). In voltage-clamped (-60 mV) oocytes, superfusion of L-phenylalanine evoked a sodium- and chloride-independent, saturable (Km = 0.34 +/- 0.02 mM, Imax = 31.3 +/- 0.5 nA), outward current. This outward current was reduced in the presence of high external [K] and was barium-sensitive. Outward currents were also evoked by L-leucine, L-glutamine, L-alanine, D-phenylalanine, and L-beta-phenylalanine. Superfusion of L-arginine evoked a saturable (Km = 0.09 +/- 0.02 mM, Imax = -29.2 +/- 1.3 nA) inward current; L-lysine and D-arginine also evoked inward currents. L-Glutamate and beta-alanine failed to evoke any currents. Effluxes of L-[3H]phenylalanine and L-[3H]arginine were trans-stimulated in the presence of either amino acid. Flux-current comparisons indicated amino acid:charge movement stoichiometry of 1:1 for both neutral and cationic amino acids. These findings indicate that the amino acid transport activity(ies) expressed in NBAT cRNA-injected oocytes is electrogenic by a mechanism including the outward movement of a net positive charge (potassium ion or cationic amino acid) in exchange for uptake of a neutral amino acid.

Amino Acid Transport Systems, Basic↗
PubMed1984

An acidic or basic amino acid at position 26 of the b subunit of Escherichia coli F1F0-ATPase impairs membrane proton permeability: suppression of the uncF469 nonsense mutation.

The uncF469 allele differed from normal in that a G----A base change occurred at nucleotide 77 of the uncF gene, resulting in a TAG stop codon rather than the tryptophan codon TGG. Two partial revertant strains were isolated which retained the uncF469 allele but formed a partially functional b-subunit, due to suppression of the uncF469 nonsense mutation. From the altered isoelectric points of the b-subunits from these strains, it was concluded that the suppressor gene of partial revertant strain AN1956 inserts an acidic amino acid for the TAG codon, and that the suppressor gene of partial revertant strain AN1958 inserts a basic amino acid. The membranes of both partial revertant strains showed impaired permeability to protons on removal of F1-ATPase. The membranes of both strains, however, were able to carry out oxidative phosphorylation, and the ATPase activities of both were resistant to the inhibitor dicyclohexylcarbodiimide.

Adenosine Triphosphatases↗
PubMed2002

Both acidic and basic amino acids in an amphitropic enzyme, CTP:phosphocholine cytidylyltransferase, dictate its selectivity for anionic membranes.

Amphitropic proteins are regulated by reversible membrane interaction. Anionic phospholipids generally promote membrane binding of such proteins via electrostatics between the negatively charged lipid headgroups and clusters of basic groups on the proteins. In this study of one amphitropic protein, a cytidylyltransferase (CT) that regulates phosphatidylcholine synthesis, we found that substitution of lysines to glutamine along both interfacial strips of the membrane-binding amphipathic helix eliminated electrostatic binding. Unexpectedly, three glutamates also participate in the selectivity for anionic membrane surfaces. These glutamates become protonated in the low pH milieu at the surface of anionic, but not zwitterionic membranes, increasing protein positive charge and hydrophobicity. The binding and insertion into lipid vesicles of a synthetic peptide containing the three glutamates was pH-dependent with an apparent pK(a) that varied with anionic lipid content. Glutamate to glutamine substitution eliminated the pH dependence of the membrane interaction, and reduced anionic membrane selectivity of both the peptide and the whole CT enzyme examined in cells. Thus anionic lipids, working via surface-localized pH effects, can promote membrane binding by modifying protein charge and hydrophobicity, and this novel mechanism contributes to the membrane selectivity of CT in vivo.

Amino Acid Sequence↗
PubMed1996

Substitution of basic amino acids in the basic region stabilizes DNA binding by E12 homodimers.

The E2A gene encodes two alternatively spliced products, E12 and E47. The two proteins differ in their basic helix-loop-helix motifs (bHLH), responsible for DNA binding and dimerization. Although both E12 and E47 can bind to DNA as heterodimers with tissue-specific bHLH proteins, E12 binds to DNA poorly as homodimers. An inhibitory domain in E12 has previously been found to prevent E12 homodimers from binding to DNA. By measuring the dissociation rates using filter binding and electrophoretic mobility shift assays, we have shown here that the inhibitory domain interferes with DNA binding by destabilizing the DNA-protein complexes. Furthermore, we have demonstrated that substitution of basic amino acids (not other amino acids) in the DNA-binding domain of E12 can increase the intrinsic DNA-binding activity of E12 and stabilize the binding complexes, thus alleviating the repression from the inhibitory domain. This ability of basic amino acids to stabilize DNA-binding complexes may be of biological significance in the case of myogenic bHLH proteins, which all possess two more basic amino acids in their DNA binding domain than E12. To function as heterodimers with E12, the myogenic bHLH proteins may need stronger DNA binding domains.

Alternative Splicing↗
PubMed2004

Deorphanization of GPRC6A: a promiscuous L-alpha-amino acid receptor with preference for basic amino acids.

One of the most important tasks of molecular pharmacology is the deorphanization of the large number of G-protein-coupled receptors with unidentified endogenous agonists. We recently reported the cloning and analysis of expression of a novel human family C G-protein-coupled receptor, termed hGPRC6A. To identify agonists at this orphan receptor, we faced the challenges of achieving surface expression in mammalian cell lines and establishing an appropriate functional assay. Generating a chimeric receptor construct, h6A/5.24, containing the ligand binding amino-terminal domain (ATD) of hGPRC6A with the signal transducing transmembrane and C terminus of the homologous goldfish 5.24 receptor allowed us to overcome these obstacles. Homology modeling of the hGPRC6A ATD based on the crystal structure of the metabotropic glutamate receptor subtype 1 predicted interaction with alpha-amino acids and was employed to rationally select potential ligands. Measurement of Ca2+-dependent chloride currents in Xenopus laevis oocytes facilitated the deorphanization of h6A/5.24 and identification of L-alpha-amino acids as agonists. The most active agonists were basic L-alpha-amino acids, L-Arg, L-Lys, and L-ornithine, suggesting that these may function as endogenous signaling molecules. Measurement of intracellular calcium in tsA cells expressing h6A/5.24 allowed determination of EC50 values, which confirmed the agonist preferences observed in oocytes. Cloning, cell surface expression and deorphanization of the mouse ortholog further reinforces the assignment of the agonist preferences of hGPRC6A. This study demonstrates the utility of a chimeric receptor approach in combination with molecular modeling, for elucidating agonist interaction with GPRC6A, a novel family C G-protein-coupled receptor.

Amino Acid Sequence↗
PubMed1997

Bilayer interactions of indolicidin, a small antimicrobial peptide rich in tryptophan, proline, and basic amino acids.

Tryptophan, proline, and basic amino acids have all been implicated as being important in the assembly and structure of membrane proteins. Indolicidin, an antimicrobial 13-residue peptide-amide isolated from the cytoplasmic granules of bovine neutrophils, is highly enriched in these amino acids: five tryptophans, three prolines, three basic residues, and no acidic residues. Consistent with the likely importance of these amino acids in membrane protein assembly, indolicidin is known to be highly membrane-active and is believed to act by disruption of cell membranes. We have, therefore, examined the interactions of native indolicidin with large unilamellar vesicles (LUV) formed from palmitoyloleoylphosphatidylcholine (POPC), and palmitoyloleoylphosphatidylglycerol (POPG), in order to use it as a model system for studying membrane protein insertion and for evaluating the relative contributions of hydrophobic and electrostatic forces in peptide-bilayer interactions. Equilibrium dialysis measurements indicate that indolicidin binds strongly, but reversibly, to both neutral POPC and anionic POPG vesicles with free energies of transfer of -8.8 +/- 0.2 and -11.5 +/- 0.4 kcal/mol, respectively. The extremely strong partitioning into POPG vesicles necessitated the development of a new equilibrium dialysis method that is described in detail. Tryptophan fluorescence measurements show that indolicidin is located in the bilayer interface and that indole fluorescence is affected by the type of lipid used to form the LUVs. Circular dichroism (CD) measurements reveal unordered conformations in aqueous and bulk organic solutions and a somewhat more ordered, but not alpha-helical, conformation in SDS micelles and lipid bilayers. Fluorescence requenching measurements (Ladokhin et al. 1995. Biophys. J. 69:1964-1971) on vesicles loaded with the fluorophore/quencher pair 8-aminonapthalene-1,3,6 trisulfonic acid (ANTS)/p-xylene-bis-pyridinium bromide (DPX), show that indolicidin induces membrane permeabilization. For anionic POPG, leakage is graded with a high preference for the release of cationic DPX over anionic ANTS. For neutral POPC vesicles no such preference is observed. Leakage induction is more effective with POPG vesicles than with POPC vesicles, as judged by three quantitative measures that are developed in the Appendix.

Animals↗
PubMed2002

Na+-independent transporters, LAT-2 and b0,+, exchange L-DOPA with neutral and basic amino acids in two clonal renal cell lines.

The present study examined the functional characteristics of L-DOPA transporters in two functionally different clonal subpopulations of opossum kidney (OKLC and OKHC) cells. The uptake of L-DOPA was largely Na+-independent, though in OKHC cells a minor component (approximately 15%) required extracellular Na+. At least two Na+-independent transporters appear to be involved in L-DOPA uptake. One of these transporters has a broad specificity for small and large neutral amino acids, is stimulated by acid pH and inhibited by 2-aminobicyclo(2,2,l)-heptane-2-carboxylic acid (BCH; OKLC, Ki = 291 mM; OKHC, Ki = 380 mM). The other Na+-independent transporter binds neutral and basic amino acids and also recognizes the di-amino acid cystine. [14C]-L-DOPA efflux from OKLC and OKHC cells over 12 min corresponded to a small amount of intracellular [14C]-L-DOPA. L-Leucine, nonlabelled L-DOPA, BCH and L-arginine, stimulated the efflux of [14C]-L-DOPA in a Na+-independent manner. It is suggested that L-DOPA uses at least two major transporters, systems LAT-2 and b0,+. The transport of L-DOPA by LAT-2 corresponds to a Na+-independent transporter with a broad specificity for small and large neutral amino acids, stimulated by acid pH and inhibited by BCH. The transport of L-DOPA by system b0,+ is a Na+-independent transporter for neutral and basic amino acids that also recognizes cystine. LAT-2 was found equally important at the apical and basolateral membranes, whereas system b0,+ had a predominant distribution in apical membranes.

Amino Acids, Basic↗
PubMed1990

Changes with aging in the levels of amino acids in rat CNS structural elements: IV. Methionine and basic amino acids.

This paper reports the distribution of methionine, histidine, lysine, arginine, and ornithine in 53 discrete brain areas of 3- and 29-month-old male Fischer 344 rats microdissected by the punch technique. Like that of the other amino acids were reported in previous papers of this series, the distribution of methionine and the basic amino acids was regionally highly heterogeneous. The ratios of levels in the areas of highest concentrations to levels in the areas of lowest concentration varied from 10 to 15 for these amino acids, except that it was 23 for arginine. This heterogeneity is also illustrated by the finding that in some areas arginine was more than 5% of the total amino acid content and in others was less than 0.5%. The distribution of methionine differed from that of the basic amino acids, which were high in hypothalamic areas and low in the limbic system. With aging, methionine and basic amino acids, like the other amino acids studied in this series, mainly decreased in level, although in a few cases increases could be seen. Significant decreases were noted more than five times as often as increases.

Aging↗
PubMed2003

Analogues of a potent oxytocin antagonist with truncated C-terminus or shorter amino acid side chain of the basic amino acid at position 8.

Twelve analogues were synthesized, their structure derived from modifications of [(S)Pmp1, D-Trp2, Pen6, Arg8]oxytocin, PA, in which (S)Pmp = beta,beta-(3-thiapentamethylene-beta-mercaptopropionic acid). PA is a potent antagonist of the uterotonic effect of oxytocin in the rat (uterotonic test in vitro, pA2 = 8.86) and in the baboon. Truncated analogues of PA from the C-terminus were systematically prepared ending in either the free acid or the amide, i.e. PA1-9 acid, PA1-8 acid, PA1-7 acid, PA1-6 acid, PA1-8 amide, PA1-7 amide and PA1-6 amide. PA1-8 amide was roughly as potent as PA in the rat uterotonic assay in vitro, and the shorter amides were only somewhat weaker antagonists. All four acid analogues were weaker antagonists than PA but still maintained rather high antagonistic potency. These findings suggest that, if these truncated acids form as metabolites in vivo, they may contribute to the overall biological effect of PA and their contribution should be taken into account. Furthermore, using these analogues, the radioimmunoassay measurements of PA may be standardized, as they may cross react with PA antibodies and interfere with the determination. In addition, five analogues were made by substituting Arg8 of PA with Lys, Orn8, Dab8, Dap8 and Cit8. All of these analogues maintained high potency as OTAs in the uterotonic assay, although their activity was only about 1.5-3 times lower than PA. The most potent analogue in the uterotonic assay, [Dap8]PA, pA2 = 8.53, had weak pressor activity (pA2 = 6.90) and no antidiuretic effect. The pressor activity was lower for all tested acids, and for PA1-6 acid it was even below the detection limit. Additionally, PA1-9 acid, PA1-7 acid and PA1-6 acid showed no antidiuretic activity. Hence, the PA1-6 acid is a potent OTA with pA2 = 8.27 and no measurable effect in the pressor or antidiuretic tests and thus it is a pure oxytocin antagonist. This fact makes it an attractive candidate for further studies on inhibition of OT biological effects and on preterm labour.

Amino Acid Sequence↗