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At least 1,009 records · Page 56Linked to original sources
PubMed1999

Experimental beta-alaninuria induced by (aminooxy)acetate.

Experimental beta-alaninuria was induced in rats by injection of (aminooxy)acetate (AOA), a potent inhibitor of aminotransferases, in order to elucidate the pathogenesis of hyper-beta-alaninemia. A 27-fold increase of beta-alanine (BALA) excretion was induced by subcutaneous injection of 1 5 mg of AOA per kg of body weight. A 13-fold and a 9-fold increase of beta-aminoisobutyric acid (BAIBA) and gamma-aminobutyric acid (GABA), respectively, were also induced simultaneously by the AOA injection. Identification of BALA and BAIBA isolated from the rat urine was performed by chromatographic and mass spectrometric analyses. The effects of AOA injection on the tissue levels of these amino acids were also studied. Contents of BALA in the liver and kidney and GABA in the brain increased significantly in response to AOA injection. The present study indicates that BALA transaminase is involved in hyper-beta-alaninemia.

Aminoisobutyric Acids↗
PubMed1989

Growth hormone regulation of DNA replication, but not insulin production, is partly mediated by somatomedin-C/insulin-like growth factor I in isolated pancreatic islets from adult rats.

We have investigated whether the previously demonstrated stimulatory actions of growth hormone on DNA synthesis and (pro)insulin biosynthesis and release of isolated adult rat islets of Langerhans are mediated by an autocrine release of somatomedin-C/insulin-like growth factor I (SM-C/IGF I). In medium containing 1% fetal calf serum, the presence of 16.7 mmol/l glucose, or 2.7 mmol/l glucose supplemented with a concentrate of essential amino acids, caused a significant increase in 3H-thymidine incorporation and insulin release compared to 2.7 mmol/l glucose alone but no increase in SM-C/IGF I release. Further supplementation with 1 microgram/ml growth hormone increased 3H-thymidine incorporation and SM-C/IGF I release within all groups, and insulin release in the 16.7 mmol/l glucose and 2.7 mmol/l plus amino acid groups. The ability of growth hormone to increase 3H-thymidine incorporation in the presence of 16.7 mmol/l glucose, but not its action on insulin release, was partly inhibited by a monoclonal antibody against SM-C/IGF I (control cultures 100%; growth hormone alone 261 +/- 27%, mean +/- SEM; growth hormone + anti-SM-C/IGF I 179 +/- 21%; p less than 0.05, n = 18). Growth hormone, but not 100 ng/ml SM-C/IGF I, increased insulin biosynthesis assessed as immunoprecipitable 3H-labelled insulin by 45%, but this was accompanied by a similar increase in overall protein synthesis. Similarly growth hormone, but not SM-C/IGF I caused a 75% increase in glucose oxidation by islets. Both growth hormone and SM-C/IGF I failed to increase the cellular uptake of alpha-aminoisobutyric acid or 3-O-methyl glucose over a 90 min period.(ABSTRACT TRUNCATED AT 250 WORDS)

3-O-Methylglucose↗
PubMed2006

Chiral interaction in Gly-capped N-terminal motif of 3(10)-helix and domino-type induction in helix sense.

Chiral interaction of helical peptide with chiral molecule, and concomitant induction in its helix sense have been demonstrated in optically inactive nonapeptide (1) possessing Gly at its N-terminus: H-Gly-(Delta(Z)Phe-Aib)(4)-OCH(3) (1: Delta(Z)Phe = Z-dehydrophenylalanine; Aib = alpha-aminoisobutyric acid). Spectroscopic measurements [mainly nuclear magnetic resonance (NMR) and circular diochroism (CD)] as well as theoretical simulation have been carried out for that purpose. Peptide 1 in the 3(10)-helix tends to adopt preferentially a right-handed screw sense by chiral Boc-L-amino acid (Boc: t-butoxycarbonyl). Induction in the helix sense through the noncovalent chiral domino effect should be derived primarily from the complex supported by the three-point coordination on the N-terminal sequence. Thus the 3(10)-helical terminus consisting of only alpha-amino acid residues enables chiral recognition of the Boc-amino acid molecule, leading to modulation of the original chain asymmetry. Dynamics in the helix-sense induction also have been discussed on the basis of a low-temperature NMR study. Furthermore, the inversion of induced helix sense has been achieved through solvent effects.

Aminoisobutyric Acids↗
PubMed1990

Blood-brain barrier disruption following CPR in piglets.

We studied blood-brain barrier (BBB) integrity in immature piglets during the following cardiopulmonary resuscitation (CPR). As in our previous work in the dog, there was no disruption during CPR after eight minutes of cardiac arrest, or immediately following resuscitation using a small molecule, alpha-aminoisobutyric acid. However, unlike the dog, where the BBB remained intact, we found delayed disruption of the BBB four hours after resuscitation. Young animals may be more prone to a delayed increase in BBB permeability after cardiac arrest and CPR.

Aminoisobutyric Acids↗
PubMed1991

A method to quantitatively measure transcapillary transport of iodinated compounds in canine brain tumors with computed tomography.

We present a quantitative method for determining a blood-to-tissue influx constant (K1), a tissue-to-blood efflux constant (k2), and tissue plasma vascular space (Vp) that uses a computed tomographic (CT) scanner to make tissue and plasma measurements of the concentration of an iodinated compound. Meglumine iothalamate was infused intravenously over time periods of 0.5-5 min, up to 49 CT scans were obtained at one brain level, and arterial plasma was sampled over a 30- to 40-min period. K1, k2, and Vp were calculated for each voxel of the 320 x 320 matrix, using a two-compartment pharmacokinetic model and nonlinear least-squares regression. The method was used in dogs with avian sarcoma virus-induced brain tumors. As many as four studies on different days were done in the same animal. In tumor-free cortex, K1 of meglumine iothalamate was 2.4 +/- 1.7 microliter g-1 min-1 (mean +/- SD) and Vp was 3.4 +/- 0.5 ml 100 g-1. Mean whole-brain tumor K1 values ranged from 3.3 to 97.9 microliters g-1 min-1; k2 ranged from 0.032 to 0.27 min-1; and Vp ranged from 1.1 to 11.4 ml 100 g-1. These values were reproducible in serial experiments in single animals. Independent verification of K1 values was obtained with quantitative autoradiographic measurements of alpha-aminoisobutyric acid, which has similar physicochemical properties to meglumine iothalamate. The CT methodology is capable of demonstrating regional variation of transcapillary transport in brain tumors and may be of value in the study of human brain tumors.

Aminoisobutyric Acids↗
PubMed2000

DNA degradation in the kidney of folic acid-treated guinea pigs.

Previous investigators agree on the increased DNA synthesis and destruction of tissues caused by folic acid (FA) administered parenterally. This study aims to clarify whether DNA degradation due to the destruction of cells and nuclei precedes DNA synthesis following FA administration. Forty guinea pigs were divided into four groups: group 1, contained 10 controls; in group 2, ten animals received intraperitoneally 300 mg/kg of body wt FA; in group 3, ten animals received FA and 12 h later frusemide intramuscularly in a dose of 7 mg/kg body wt; and finally in group 4, ten animals received frusemide as in group 3. FA produced necrosis of the epithelial cells of the convoluted tubules as the detection of the beta-aminoisobutyric acid end product of DNA and thymine catabolism indicated. Frusemide administered in group 3 had a favourable effect on the acute renal failure induced by FA.

Acute Kidney Injury↗
PubMed1976

Blockade of prolactin action by an antiserum to its receptors.

A guinea pig antiserum to prolactin receptors selectively inhibited the binding of [125I] prolactin to its membrane receptors as well as prolactin-mediated incorporation of [3H] leucine into casein and transport of [14C] aminoisobutyric acid, but was without effect on the binding of [125I] insulin and insulin-mediated events in explants of rabbit mammary glands maintained in culture. These findings provide direct evidence for an obligatory functional role of a membrane receptor in mediating the action of a polypeptide hormone.

Aminoisobutyric Acids↗
PubMed2005

Evidence against the hopping mechanism as an important electron transfer pathway for conformationally constrained oligopeptides.

The rate constant of intramolecular electron transfer through oligopeptides based on the alpha-aminoisobutyric acid residue was determined as a function of the peptide length and found to depend weakly on the donor-acceptor separation. By measuring the electron-transfer activation energy and estimating the energy gap between donor and bridge, we were able to discard the electron hopping mechanism.

Amides↗
PubMed1979

Uptake of glycine by human kidney cortex.

The transport of glycine was investigated in histologically normal adult human kidney cortical slices. Uptake occurs against a gradient and shows concentration dependence. Kinetic analysis reveals two systems for transport of glycine with apparent transport Km values of 0.511 and 34.2 mM. Glycine transport on the high-Km system is competitively inhibited by 50 mML-proline. Transport inhibition on the low-Km system could not be directly evaluated, but on theoretic grounds appears not to be inhibited by L-proline or hydroxyproline. Alpha-aminoisobutyric acid, valine, and thioproline are also shown to inhibit glycine uptake. Low medium sodium or anaerobic incubation depress the uptake of glycine. These observations are consistent with previous reports of glycine transport in rat kidney and support the proposals for the mechanism of familial iminoglycinuria based on in vivo investigations.

Adult↗
PubMed1971

Insulin-sepharose and the dynamics of insulin action.

In terms of the rate of accumulation of alpha-aminoisobutyric acid, mammary epithelial cells from mature virgin mice respond rapidly to insulin covalently bound to sepharose particles, but do not respond initially to soluble insulin in vitro. The response to insulin-sepharose is prevented if the cells are first exposed to insulin. These observations may provide new insight into the dynamics of insulin action.

Aminoisobutyric Acids↗
PubMed1977

Transport capacity, alkaline phosphatase activity and protein content of glutaraldehyde-treated cell forms of Escherichia coli.

Studies on the comparative transport capacity of various cell forms of Escherichia coli suggest that glutaraldehyde acts only in the outer regions of the cell envelope and to such an extent that transport of alpha-aminoisobutyric acid is reduced by 50%. Alkaline phosphatase activity in whole cells was severely impaired in the presence of alkaline glutaraldehyde and in NaCl-washed cells both acid and alkaline glutaraldehyde (0.01%) caused approximately 80-90% reduction in enzyme activity in 10 min. Protein content was reduced by only 10-15% with this concentration of glutaraldehyde, and cell volume decreased by the same extent. These results are discussed in terms of the mode of action of the disinfectant.

Aldehydes↗
PubMedDate not supplied

Cell proliferation and metabolism of Ehrlich ascites tumor cells grown in chemically defined albumin medium for several passages.

Cell proliferation, cell cycle distribution, viability, uptake of alpha-aminoisobutytic acid, cyclo leucine and 2-deoxyglucose as well as DNA, RNA and protein synthesis of Ehrlich ascites tumor cells grown in suspension culture over three passages in serum free nutrient medium supplemented with 1-2% bovine serum albumin) Cohn fraction V, Serva) were measured and compared to cells grown in medium supplemented with 15% horse serum. At the end of the fourth passage in vitro, that is the third passage in serum free albumin medium, the growth of the cells is reduced to about 10% of the controls, accumulation of the cells in G2 is delayed and the number of dead cells rises to 30%. The transport rates of alpha-aminoisobutyric acid and of 2-deoxyglucose slowly decrease while the uptake of cycloleucine shows a more complex behaviour in albumin medium. Incorporation of thymidine and leucine into the cells corresponds to the growth rate, while the incorporation of uridine in normal as well as in albumin medium exhibits different pattern. The present experiments demonstrate, that it may be possible to preserve this cells in a fairly "physiological" state during two passages in albumin medium.

Aminoisobutyric Acids↗
PubMed2000

Conformational restriction through C alpha i <--> C alpha i cyclization: Ac12c, the largest cycloaliphatic C alpha,alpha- disubstituted glycine known.

Two complete series of N-protected, monodispersed oligopeptide esters to the pentamer level from 1-aminocyclododecane-1-carboxylic acid (Ac(12)c), an alpha-amino acid conformationally constrained through C(alpha)(i) <--> C(alpha)(i) cyclization, and either L-Ala or Aib residues, along with the N-protected Ac(12)c homopeptide alkylamide series from monomer to trimer, have been synthesized by solution methods and fully characterized. The solution-preferred conformations of these peptides have been assessed by Fourier transform ir absorption and (1)H-nmr techniques. Moreover, the molecular structures of one derivative (Z-Ac(12)c-OH) and three peptides [the tripeptide ester Z-L-Ala-Ac(12)c-L-Ala-OMe, the tripeptide alkylamide Z-(Ac(12)c)(3)-NHiPr, and the tetrapeptide ester Z-(Aib)(2)-Ac(12)c-Aib-OtBu (Aib, alpha-aminoisobutyric acid)] have been determined in the crystal state by x-ray diffraction. The results obtained point to the conclusion that beta-bends and 3(10)-helices are preferentially adopted by peptides based on Ac(12)c, the largest cycloaliphatic C-disubstituted glycine known. A comparison with the structural tendencies extracted from published works on peptides from Aib, the prototype of C-disubstituted glycines, and the other extensively studied members of the class of 1-aminocycloalkane-1-carboxylic acids (Ac(n) c, with n = 3-9), is made and the implications for the use of the Ac(12)c residue in the Ac(n) c scan approach of conformationally restricted analogues of bioactive peptides are briefly discussed.

Alanine↗
PubMed1986

Response ot insulin by thymocytes of adrenalectomized and adrenalectomized-diabetic rats.

Insulin receptors and he hormone action "in vitro" and "in vivo" on alpha-aminoisobutyric acid (AIB) uptake were studies on thymocytes from adrenalectomized and adrenalectomized-diabetic rats. The lack of insulin effect "in vitro" correlated with the absence of insulin receptors. Meanwhile the increase in AIB uptake produced by an injection of insulin suggest an indirect action of the hormone that could be the consequences of metabolic events.

Adrenalectomy↗
PubMed1986

Long polypeptide 3(10)-helices at atomic resolution.

The crystal-state preferred conformation of the terminally blocked homooctapeptide from the C(alpha,alpha)-dimethylated alpha-aminoisobutyric acid (Aib) residue, pBrBz-(Aib)(8)-OBu(t), in which pBrBz is para-bromobenzoyl and OBu(t) is tert-butoxy, determined by x-ray diffraction analysis using direct methods, was found to be a 3(10)-helix stabilized by six consecutive intramolecular N-H....O=C hydrogen bonds of the C(10)-III (or III') type. This is the first observation at atomic resolution of a regular 3(10)-helix longer than two complete turns. The solid-state structural analysis was extended to the terminally blocked, alpha-aminoisobutyric acid-rich octapeptide corresponding to the 2-9 sequence of the peptaibol antibiotics emerimicins III and IV, pBrBz-Aib(3)-L-Val-Gly-L-Leu-Aib(2)-OMe. Again, this peptide adopts a (right-handed) 3(10)-helical structure, although slightly distorted at the level of the L-leucine residue. The role of specific amino acid sequence and peptide main-chain length in stabilizing either the 3(10)- or the alpha-helical conformation and their possible implications on the nature of the channel formed by peptaibol antibiotics in the membrane are also briefly discussed.

Journal Article↗
PubMed1993

Crystal structures of Boc-D- and L-Iva-L-Pro-OBzl: unturned conformation of Aib-Pro sequence unaffected by replacement of Me with Et in Aib.

The crystal structures of the isovaline (Iva) containing dipeptides, Boc-D-Iva-L-Pro-OBzl and Boc-L-Iva-L-Pro-OBzl, were determined by x-ray diffraction. The diastereomeric peptides were shown to adopt unturned conformations closely similar to each other (phi Iva 52 degrees, psi Iva 46 degrees, phi Pro -65 degrees, and psi Pro 143 degrees for D-Iva-L-Pro sequence and phi Iva 52 degrees, psi Iva 44 degrees, phi Pro -63 degrees, and psi Pro 148 degrees for L-Iva-L-Pro sequence). The Pro ring of each peptide was in C gamma-endo conformation. The unusually large angle CIva-NPro-C delta Pro values (131 degrees in both peptides) were observed, that was due to steric repulsion between the delta-methylene of Pro and the alkyl side chain of Iva residue. These conformations were essentially the same as that of the corresponding alpha-aminoisobutyric acid (Aib)-containing peptide Boc-Aib-L-Pro-OBzl. The result has demonstrated that replacement of either one of the two methyl groups of the Aib residue in Boc-Aib-L-Pro-OBzl with an ethyl group does not cause any significant change in the unturned conformation of the dipeptide.

Aminoisobutyric Acids↗
PubMed1990

Effects of internal carotid administration of MPTP on rat brain and blood-brain barrier.

Unlike primates, rats are resistant to systemic 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) neurotoxicity, but direct infusion of MPTP into rat substantia nigra causes specific destruction of dopaminergic neurons. We now demonstrate that rats are resistant to MPTP neurotoxicity even when MPTP is injected directly into the brain circulation. Injection of 1-3.5 mg of MPTP into the internal carotid artery of Wistar rats causes no behavioral or motor abnormalities and small, but significant, dopamine loss in the ipsilateral striatum. MPTP caused no changes in the levels of norepinephrine or serotonin in the cerebral cortex. Higher doses of intracarotid MPTP were lethal. Pretreatment with pargyline, a monoamine oxidase inhibitor, did not alter the mortality but prevented dopamine depletion. The high uptake and retention of MPTP by rat brain, yet its failure to cause major dopaminergic toxicity suggest that MPTP is rapidly metabolized in brain capillaries to 1-methyl-4-phenylpyridinium (MPP+) and other polar metabolites that have difficulty in traversing the blood-brain barrier. Sequestration of MPTP metabolites in brain capillary endothelial cells could result in their dysfunction. However, we found no defects in the ability of the blood-brain barrier to prevent the entry of vascular aminoisobutyric acid or horseradish peroxidase into brain in spite of morphologic evidence of endothelial changes and astrocytic swelling after intracarotid MPTP injections. Our results provide further evidence that the rat's resistance to systemic MPTP neurotoxicity is probably due to its unique blood-brain barrier properties.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗