Disease relevance of beta-alanine

• The massive amounts of beta-aminoisobutyric acid (beta-AIBA) in the urine of Burkitt's lymphoma patients were measured along with other alpha-amino acids and beta-alanine present in normal and decreased levels [1].
• L-Aspartate-alpha-decarboxylase, an enzyme that catalyzes the production of beta-alanine, has been purified to apparent homogeneity from Escherichia coli [2].
• An enzyme which catalyzes the transamination of beta-alanine with alpha-ketoglutarate was purified to homogeneity from Streptomyces griseus IFO 3102 and crystallized [3].
• Systolic blood pressure 3 and 4 weeks after the administration of beta-alanine was slightly, but not significantly, lower than that of untreated rats on a high-salt diet, and was accompanied by a significantly lower body weight [4].
• Pantothenate synthetase from Mycobacterium tuberculosis catalyzes the formation of pantothenate from ATP, D-pantoate, and beta-alanine [5].

High impact information on beta-alanine

• Whereas wild-type alpha 1 channels expressed in Xenopus oocytes required 0.7 millimolar beta-alanine for a half-maximal response, the doubly mutated (F159Y,Y161F) alpha 1 subunit had an affinity for beta-alanine (which was more potent than glycine) that was 110-fold that of the wild type [6].
• A conjugate containing a beta-alanine residue at the C terminus of the polyamide moiety showed no nuclear localization, whereas an analogous compound lacking the beta-alanine residue was strongly localized in the nuclei of all cell lines tested [7].
• However, the calculated isoelectric point of the taurine/beta-alanine transporter is more acidic (pI = 5.98) than those (pI > 8.0) of other cloned neurotransmitter transporters [8].
• At this survival time, 61% of the radioactivity in the olfactory epithelium was present in the carnosine fraction, while 37% of the label remained in the beta-alanine fraction [9].
• From these results, we concluded that TGR7 functioned as a specific membrane receptor for beta-alanine [10].

Chemical compound and disease context of beta-alanine

• RESULTS: In vitro competitive binding assays, using PC-3 androgen-independent human prostate cancer cells, demonstrated values of <2.5 nmol/L for inhibitory concentration of 50% for analogs with beta-Ala, 5-Ava, and 8-Aoc spacers [11].
• Ingestion by neither 0.1 M taurine alone nor 0.1 M beta-alanine, a taurine transport antagonist, produced any evidence of hypernatremia throughout the experiment [12].
• METHODS: An 11-base PMO (AcpP) targeted at acpP (an essential gene) of Escherichia coli was synthesized and conjugated with the cell-penetrating peptide RFFRFFRFFRXB (X is 6-aminohexanoic acid and B is beta-alanine) [13].
• Urinary biomarkers of each class of toxicity were elucidated from the PC loadings and included organic acids, amino acids, and sugars in the case of mercury, while levels of taurine, beta-alanine, creatine, and 2-aminoadipate were elevated after hydrazine treatment [14].
• Escherichia coli beta-alanine auxotrophs (panD2) were used to manipulate the specific cellular content of coenzyme A (CoA) and assess the associated physiological effects [15].

Biological context of beta-alanine

• These results indicate that harmaline does not compete with sodium for a binding site on the carrier as has been suggested for other sodium-coupled transport systems, and that instead, chloride may be required for harmaline binding to the beta-alanine transporter [16].
• In this report, a combination of beta-alanine scanning mutagenesis and kinetic measurements was used to probe, in a quantitative, systematic, and simultaneous fashion, the relative contribution of the amino acid side chain and backbone functionalities to the overall calpain-inhibitory activity of B27-WT [17].
• Recent studies in a variety of transport systems, including rat renal brush border membrane vesicles, indicate that halide anions chloride (Cl-) and bromide (Br-) are essential for glycine, beta-alanine, gamma-aminobutyric acid, and taurine uptake, so the possibility that Na(+)-proline symport is Cl- dependent was explored [18].
• An LLC-PK1 cell line stably expressing GABA transporter type 3 (GAT-3), a beta-alanine-sensitive neuronal GABA transporter, has been generated and used to examine the kinetics, ion dependence, and pharmacological properties of the transporter [19].
• The biosynthesis begins with the decarboxylation of aspartate to give beta-alanine [20].

Anatomical context of beta-alanine

• Sodium-dependent beta-alanine uptake into dog renal brush-border membrane vesicles was studied [16].
• When a fusion protein composed of TGR7 and green fluorescent protein was expressed in cells, it localized at the plasma membrane but internalized into the cytoplasm after treatment with beta-alanine [10].
• Na(+)-independent, H(+)-coupled transepithelial beta-alanine absorption by human intestinal Caco-2 cell monolayers [21].
• To examine the role of beta-alanine (beta ALA) in cellular metabolism, we cultured her skin fibroblasts in medium containing increasing amounts of beta ALA [22].
• The maximal uptake rates (Vmax) determined were such that, in neurons, Vmax GABA greater than Vmax beta-Ala = Vmax Tau, whereas in astrocytes, Vmax beta-Ala greater than Vmax Tau = Vmax GABA [23].

Associations of beta-alanine with other chemical compounds

• Using a functional screen in the yeast Saccharomyces cerevisiae, a putative amine oxidase, encoded by FMS1, was found to be rate-limiting for beta-alanine and pantothenic acid biosynthesis [24].
• The pharmacology of GAT2 is different from that of GAT1 because of lack of inhibition by guvacine and nipecotic acid and sensitivity to high concentrations of betaine and beta-alanine [25].
• GAT2 transports betaine with a Km of about 200 microM, but no significant transport of beta-alanine could be detected [25].
• The homology of FMS1 to FAD-containing amine oxidases and its role in beta-alanine biosynthesis suggested that its substrates are polyamines [24].
• In guanosine 5'-O-3-thiotriphosphate binding assays conducted using a membrane fraction of cells expressing TGR7, beta-alanine specifically increased the binding of guanosine 5'-O-3-thiotriphosphate [10].

Gene context of beta-alanine

• Like the homologous beta-alanine synthases, NLP1 showed positive cooperativity toward its substrate [26].
• Evidence is presented that beta-alanine is transported by the general amino acid permease Gap1p [27].
• GAT3 also transports beta-alanine and taurine with Km of 28 and 540 microM, respectively [28].
• Under conditions where NHE3 is inactive (the absence of Na(+), apical pH 5.5, the presence of the NHE3 inhibitor S1611) no regulation of beta-alanine uptake is observed [29].
• Activation of the cAMP/protein kinase A pathway in Caco-2 cell monolayers either using pharmacological tools (forskolin, 8-br-cAMP, [(11,22,28)Ala]VIP) or physiological activators (the neuropeptides VIP and PACAP) inhibited hPAT1 function (beta-alanine uptake) at the apical membrane [29].

Analytical, diagnostic and therapeutic context of beta-alanine

• Crude venom was fractionated by anion exchange and gel filtration in four steps. beta-Alanine acetate disk gel electrophoresis was used to demonstrate electrophoretic homogeneity [30].
• However, the isomeric pairs could be resolved by reversed-phase high performance liquid chromatography, with the reverse amides having greater retention times compared to the beta-alanine conjugates [31].
• Growth of SJ16/pKAS4 on [3H]-beta-alanine followed by Coomassie staining of the protein and autoradiography revealed that PHA synthase is overexpressed and that beta-alanine is incorporated into the protein [32].
• The reverse amide analogs comigrated with their isomeric beta-alanine conjugates during thin-layer chromatography using a variety of solvent systems [31].
• Two synthetic analogues of distamycin (Dst), PPA and PAP, containing a saturated beta-alanine moiety substituting for an N-methylpyrrole chromophore were studied for their interactions with the double-stranded alternating copolymer poly(dA-dT).poly(dA-dt) [abbreviated as poly(dA-dT)], with UV absorption and circular dichroism (CD) spectroscopy [33].

References