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PubMedDate not supplied

Elevated urinary excretion of beta-aminoisobutyric acid and exposure to inorganic lead.

beta-Aminoisobutyric acid (beta-AIB), a normal degradation product of thymine, a constituent of DNA and, to a lesser extent, of transfer RNA, is excreted in low levels in human urine. We found that a group of iron workers occupationally exposed to inorganic lead excreted high levels of urinary beta-AIB. Elevated urinary excretion of beta-AIB was also observed in marmosets, Callithrix jacchus, that received lead acetate in drinking water. Our results suggest that increased urinary excretion of beta-AIB could stem from damage to DNA on exposure to lead.

Adult↗
PubMed1977

Sodium ion-stimulated alpha-[1-14C]aminoisobutyric acid uptake in alkalophilic Bacillus species.

Alkalophilic Bacillus no. 8-1 grows well in alkaline media containing 2.5 to 5% NaCl. The uptake of alpha-aminoisobutyric acid (AIB) into the cells is stimulated by the addition of NaCl (Na+) up to a concentration of 0.2 M, but other monovalent cations such as K+, Li+, or NH4+ cannot substitute for Na+. The kinetic studies reveal that, when the Na+ concentration increases from 0.02 to 0.2 M in alkaline medium, the Km for transport decreases, whereas Vmax remains almost constant. Competition studies indicate that glycine, L-alanine, L-serine, and AIB share common carriers for the transport of the compounds into cells. Other alkalophilic bacteria are also found to require Na+ for the uptake of AIB into the cells.

Amino Acids↗
PubMed1980

The complete rate equation, including the explicit dependence on Na+ ions, for the influx of alpha-aminoisobutyric acid into mouse brain slices.

The rate equation, including dependence on Na+-ion concentration for the influx of alpha-aminoisobutyric acid into mouse brain slices incubated in isotonic glucose medium at 37 degrees C, is v = 0.402 S/(1.02(1 + 788/[Na+]2)+S)+0.0477S, where v = influx in mu mol/min, g final wet wt of slices; [Na+] = concentbutyric acid in medium, in mM. This equation shows two kinetically independent, parallel pathways of concentrative uptake: one, saturable and dependent on Na+; the other, unsaturable and independent of Na+. Influx is independent of ionic strength, Cl- ion per se, and a moderate increase in tonicity. The binding of substrate to the saturable carrier depends on the Na+ concentration; the maximum capacity of this carrier does not. For transport, 2 Na+ ions must interact with each saturable transport site. This does not imply coupling between the flux of Na+ and the flux of alpha-aminoisobutyric acid.

Aminoisobutyric Acids↗
PubMed1977

[Variations in alpha-aminoisobutyric acid transport during in vitro differentiation of cultured myocardial cells from newborn rats].

The transport of alpha-aminoisobutyric acid has been studied as a function of age in heart cell cultures derived from new-born Rats. The specific rate of alpha-aminoisobutyric acid transport decreased slightly once confluency had been reached and then, from day 8 on, increased abruptly. This last phase may be related to the expression of specialized functions encountered in older cultures.

Aminoisobutyric Acids↗
PubMed1985

Increased beta-aminoisobutyric acid in rat liver with 6-azauracil and its enantiomer.

When 6-azauracil was subcutaneously injected, beta-aminoisobutyric acid and beta-alanine contents were increased 22 and 61-fold, respectively, in rat liver. Incorporation of [methyl-14C]thymine into beta-aminoisobutyric acid was increased to 42-fold by 6-azauracil treatment. The absolute configuration of this amino acid was proved to be the (R)-form by means of a gas-chromatographic technique. 6-Azauracil inhibited beta-alanine-pyruvate aminotransferase activity with an I50 of approx. 2.5 mM.

Aminoisobutyric Acids↗
PubMed1980

Infrared studies on the conformation of synthetic alamethicin fragments and model peptides containing alpha-aminoisobutyric acid.

Infrared studies of synthetic alamethicin fragments and model peptides containing alpha-aminoisobutyric acid (Aib) have been carried out in solution. Tripeptides and larger fragments exhibit a strong tendency to form beta turns, stabilized by 4 leads to 1 10-atom hydrogen bonds. Dipeptides show less well-defined structures, though C5 and C7 conformations are detectable. Conformational restrictions imposed by Aib residues result in these peptides populating a limited range of states. Integrated intensities of the hydrogen-bonded N-H stretching band can be used to quantitate the number of intramolecular hydrogen bonds. Predictions made from infrared data are in excellent agreement with nuclear magnetic resonance and X-ray diffraction studies. Assignments of the urethane and tertiary amide carbonyl groups in the free state have been made in model peptides. Shifts to lower frequency on hydrogen bonding are observed for the carbonyl groups. The 1--6 segment of alamethicin is shown to adopt a 3(10) helical structure stabilized by four intramolecular hydrogen bonds. The fragments Boc-Leu-Aib-Pro-Val-Aib-OMe (12--16) and Boc-Gly-Leu-Aig-Pro-Val-Aib-OMe (11--16) possess structures involving 4 leads to 1 and 5 leads to 1 hydrogen bonds. Supporting evidence for these structures is obtained from proton nuclear magnetic resonance studies.

Alamethicin↗
PubMed1980

Correlations of beta-aminoisobutyric acid in 8 hour and 24 hour urinary samples determined by dual column gas chromatography.

The correlations of beta-aminoisobutyric acid values in 8 hour and 24 hour urinary samples from 23 healthy persons were determined. beta-AIB in the 8 hour urinary samples was measured by gas chromatography and the 24 hour excretion was calculated from the results of three 8 hour determinations. Simultaneous determinations of urinary creatinine were performed by Jaffe's reaction. Based on the 8 hour values of urinary beta-AIB the results demonstrated a constant excretion of beta-aminoisobutyric acid within the 24 hour periods in both low and high excretors. The precision in distinguishing low and high 24 hour excretors of beta-AIB by using 8 hour values was 91%. If 8 hour values of beta-AIB were related to creatinine the same precision for this calculated ratio was 96.5%. However, for high excretors of beta-AIB, failures were 24.5% by using the 8 hour excretion of beta-AIB as indicator, but only 6.5% by using the ratio.

Adolescent↗
PubMed1993

[Ecogenetic aspects of the study of phenotypes and levels of beta-aminoisobutyric acid excretion].

The levels of excretion of beta-aminoisobutyric acid (BAIB) in urea were examined in five groups. The distribution of BAIB concentration revealed the existence of high and low excretors in each group. Asbestosis patients had the lowest frequency of high excretors. The BAIB concentration among high excretors was similar for all the groups. The BAIB levels of low excretors varied. The most alike were two children groups, asbestosis patients and the workers from the town Asbest.

Aminoisobutyric Acids↗
PubMed2004

Urinary excretion of beta-aminoisobutyric acid in hematological diseases.

The level of beta-aminoisobutyric acid (beta-AIB), a thymine catabolite, has been measured in urine samples of 160 healthy individuals, 28 patients with renal, 27 patients with cardiovascular and 27 patients with hematological diseases and of 36 tumor patients. No significant difference in the prevalence of high excretors of beta-AIB between patients with cancer, renal and cardiovascular diseases and the healthy group was found, whereas all but two patients with hematological diseases were high excretors. Urinary beta-AIB shows a reverse correlation with the hemoglobin level and erythrocyte count in the cases of anemia, and appears to be directly correlated with the leukocyte count and blast cell content in the cases of leukemia, with its amount decreasing two to five-fold with the return of the hematological markers to normal levels after medicinal treatment. Therefore the beta-AIB concentration in urine may be used in combination with hematological indicators in assessing the disease status and in monitoring of the treatment response.

Adolescent↗
PubMed1975

A study on the clinical significance of urinary beta-aminoisobutyric acid in patients with urothelial tumours.

Urinary beta-aminoisobutyric acid (beta-AIB) has been measured in 141 patients with urothelial tumours and 60 controls. Ninetyone of the patients have been followed-up for an average period of about 2 years, which included many determinations of the beta-AIB excretion. Thirtysix patients died during the control periods. Urinary beta-AIB was found to be significantly correlated to the grade of tumour cell dysplasia, but not to the clinical tumour stage. The treatment had no major influence on the excretion. Characteristic changes in the excretion preceding high-grade tumour recurrences are demonstrated. Autopsy findings with tumour tissue in the urinary tract and distant metastases were significantly correlated to a low urinary beta-AIB in the terminal phase of the disease. The results are discussed in relation to the degradation of thymine, the dual origin of beta-AIB and the tumour-host metabolism. It is concluded, that urinary beta-AIB can contribute to the graduation of malignancy, but is not valuable as a general screening procedure for urothelial cancer.

Aged↗
PubMed1993

Urinary excretion patterns of pseudouridine and beta-aminoisobutyric acid in patients with tumours of the urinary bladder.

The preoperative and postoperative values of urinary pseudouridine:creatinine (phi:C) and beta-aminoisobutyric acid:creatinine (beta AIB:C) were estimated, in 192 patients with urothelial tumours of the bladder, 92 of whom had not previously been diagnosed. Urinary phi:C ratio correlated with the grade of tumour cell dysplasia (being highest in dysplasia grade 3), and to a lesser extent with the clinical stage. The treatment had no major influence on the excretion ratios. Decreased ratios, or those within the reference range, were associated with a better prognosis than increased ratios, and if both were increased at the same time the risk for progression of the disease was high. The biological tumour markers pseudouridine and beta-aminoisobutyric acid may be helpful in the diagnosis of tumours in the upper urinary tract, and in the follow-up of patients with tumours of the bladder.

Adult↗
PubMed1991

A comparative study on interactions of alpha-aminoisobutyric acid containing antibiotic peptides, trichopolyn I and hypelcin A with phosphatidylcholine bilayers.

Interactions of alpha-aminoisobutyric acid containing antibiotic peptides, trichopolyn I and hypelcin A with phosphatidylcholine bilayers were investigated to obtain some basic information on their bioactive mechanisms. Trichopolyn I as well as hypelcin A induced the leakage of a fluorescent dye, calcein, entrapped in sonicated egg yolk L-alpha-phosphatidylcholine vesicles. A quantitative analysis revealed that both the binding affinity and the 'membrane-perturbing activity' of trichopolyn I to the vesicles are about one-third of those of hypelcin A. The conformations and the orientations of the peptide and lipid molecules in the membranes were studied using polarized Fourier transform infrared-attenuated total reflection spectroscopy, circular dichroism, and differential scanning calorimetry. In phosphatidylcholine bilayers, both peptides mainly conformed to helical structures irrespective of the membrane physical state (gel or liquid-crystalline). The helix axes, penetrating the hydrophobic region of the bilayers, were oriented neither parallel nor perpendicular to the membrane normal. The disruption in the lipid packing induced by the peptide insertion seems to be responsible for the leakage by these peptides.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1982

Testing for cis' proline with alpha-aminoisobutyric acid substitution. N.m.r. studies of AIB substituted bradykinins.

Substitution of Pro residues with AIB (alpha-aminoisobutyric acid) residues in peptides provides a means of evaluating the presence of cis' proline conformations both in solution and, using bioassay data, in a receptor complex. 1H n.m.r. has been used to probe the DMSO solution conformation of all seven of the possible AIB/Pro isomers of bradykinin. AIB substitution for Pro2 and/or Pro3 appears to stabilize a type III beta-turn involving the N-terminal residues, but not an incipient 3(10) helix suggested by model peptides. These substitutions are correlated with low biological potencies, suggesting that such conformational features may be incompatible with receptor complexation. Alternatively, AIB7 -bradykinin analogs exhibit a variety of long range shift perturbations relative to bradykinin. The data suggests that bradykinin can adopt several folded conformations, including beta-turns involving both Ser6-Pro7-Phe8-Arg9 and Phe5-Ser6-Pro7-Phe8. The relatively high biological activities of the AIB7-BK suggest that the complexed form of the peptide is characterized by a cis' Pro7 conformation.

Amino Acid Sequence↗
PubMed1989

Hypelcin A, an alpha-aminoisobutyric acid containing antibiotic peptide, induced permeability change of phosphatidylcholine bilayers.

Interactions of hypelcin A, an alpha-aminoisobutyric acid containing antibiotic peptide, with phosphatidylcholine vesicles were investigated to obtain information on its bioactive mechanism. The peptide induced the leakage of a fluorescent dye, calcein, entrapped in sonicated vesicles. The leakage rate depended on both the peptide and the lipid concentrations. Analysis of this dependency indicated that the leakage was due to the monomeric peptide and that the membrane-perturbing activity of the monomer was higher for solid distearoylphosphatidylcholine vesicles than for fluid egg yolk phosphatidylcholine vesicles. Hypelcin A also affected the gel to liquid-crystalline phase transition of dipalmitoylphosphatidylcholine multilamellar vesicles. The transition was broadened with a reduced transition enthalpy, suggesting the peptide strongly binds the surrounding lipids to perturb the bilayer lipid packing. A circular dichroism study revealed that the helical content of hypelcin A increases upon membrane binding. We concluded that the monomeric peptide with an increased helical content, complexed with the lipids, perturbs the lipid organization and induces the increased permeability.

Alamethicin↗
PubMed1985

"Exchange diffusion": rate equations for the influx of alpha-aminoisobutyric acid into mouse cerebrum slices containing this amino acid.

Rate equations for the gross influx of alpha-aminoisobutyric acid (AIB) into mouse cerebrum slices containing AIB have a first-order term for unsaturable concentrative influx, identical to the corresponding term for unloaded slices, and a modified Michaelis-Menten term, V'max/(1 + Kt/S), for saturable concentrative influx. [V'max identical to v'L(1 + Kt/S), where v'L = saturable component of influx, S = AIB concentration in medium, and Kt = Michaelis constant for unloaded slices.] Below a tissue AIB (T) of 19 mumol/g final wet weight, V'max increases linearly following V'max = V1 + m1T; above that value, Vmax is virtually constant. The transition is sharp. This equation is consistent with a carrier model for active transport. At the transition, intracellular AIB is about 1 molecule for every 70 amino acid residues of tissue protein, vastly more than could be accommodated by AIB-binding sites in cell membranes. The transition may come from a slow process that does not fill all sites when the tissue AIB is below the transition concentration, or from an AIB-induced phase transition in the membrane.

Aminoisobutyric Acids↗
PubMed1985

A rat model for the study of transplacental pharmacokinetics and its assessment with antipyrine and aminoisobutyric acid.

The suitability of a pregnant rat model for the study of transplacental pharmacokinetics was assessed by two test agents, antipyrine, which freely equilibrates in the maternal and fetal blood, and aminoisobutyric acid, which is actively transported from mother to fetus. In accordance with an ideal protocol for a two-compartment model solved for bolus injections, unlabeled antipyrine was injected into the mother (day 20 of gestation), and labeled antipyrine was injected into its fetuses following exteriorization under ether anesthesia. Maternal and fetal blood samples (2-3 fetuses removed at each time period) were collected sequentially under brief periods (2-3 min) of ether anesthesia up to 9-12 hr. In separate studies it was found that sequential removal of fetuses did not significantly alter maternal or fetal serum drug concentrations. As expected, placental clearances (ml/h-1/kg-1) of antipyrine from mother to fetus (392 +/- 86) and from fetus to mother (448 +/- 107) did not significantly differ. As an alternate approach, (3H)aminoisobutyric acid was either injected into the mother or into the fetuses, and maternal and fetal blood samples were sequentially collected in each case; the clearance of this agent from fetus to mother was 53 ml/h-1/kg-1, and, as expected, was much lower than that from mother to fetus (168 ml/h-1/kg-1). It is suggested that the pregnant rat model can be used as a substitute for the chronically catheterized pregnant sheep model for the study of pharmacokinetics in the maternal-fetal unit.

Aminoisobutyric Acids↗