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PubMedDate not supplied

Asymmetrical transfer of alpha-aminoisobutyric acid (AIB), leucine and lysine across the in vitro perfused human placenta.

The mechanism for establishing transplacental gradients for leucine, lysine and alpha-aminoisobutyric acid (AIB) has been investigated in the perfused human placenta. Experiments were done with either the maternal or the fetal circulation closed and the donor circulation open. Transfer of the amino acids towards the fetal side was more rapid than it was in the reverse direction. When the maternal perfusate was recirculated, the amino acid concentrations were maintained at a considerably lower level in the maternal circulation than in the open fetal circuit. When the fetal circuit was closed, the concentrations approached or slightly exceeded those in the maternal perfusate over a period of three hours. Within the placenta, higher concentrations were established during the experiments with transfer towards the fetal side than in the reverse direction. Of the three amino acids, leucine was transferred most rapidly across the placenta while AIB reached the highest concentrations in the placental tissue. The asymmetry of the transplacental amino acid flux is favoured by rapid uptake from the maternal circulation and transfer towards the fetus. Both rates exceed those observed in the reverse direction. The transfer rate of D-leucine was 1.7 times that of L-glucose. For in vitro studies of the transfer rate of physiological compounds a correction for diffusion is required. The results may differ considerably depending on which marker is used as the basis.

Aminoisobutyric Acids↗

PubMed1990

Inhibition of alpha-aminoisobutyric acid uptake by mastoparan in Madin-Darby Canine Kidney cells.

Mastoparan, a wasp venom, was found to inhibit Na(+)-dependent net alpha-aminoisobutyric acid (AIB) uptake in Madin Darby Canine Kidney (MDCK) cells. Mastoparan also produced a significant increase in AIB efflux when compared to controls. Pretreatment of MDCK cells with 2 mM neomycin attenuated mastoparan's inhibition of net AIB uptake and completely suppressed mastoparan-mediated increases in AIB efflux when compared to controls. These data suggest that mastoparan's inhibition of net AIB uptake involves more than a single basic mechanism.

Aminoisobutyric Acids↗

PubMed1982

Stimulation of transport of alpha-aminoisobutyric acid into the testes of immature mice in vivo by follicle-stimulating hormone.

Groups of immature mice were injected sc with radiocarbon-labelled alpha-aminoisobutyric acid (AIB) after being given a single sc injection of hFSH or of 0.9% saline. As an index of the transport of AIB, the specific activity of isotope was measured in homogenates of testis and of liver. FSH treatment caused statistically significant increases in the specific activity of isotope in the testes and in the ratio of testicular to liver specific activity. The effect was greatest in 9-day-old mice injected with FSH 16 h before removal of the testes. Uptake of labelled AIB was not stimulated after administration of hCG or testosterone. Doses of cycloheximide sufficient to reduce the rate of protein synthesis by over 99% did not impair testicular uptake of labelled AIB or the influence of FSH on AIB uptake. These results suggest that FSH stimulates amino acid transport into cells of the immature testis and that this action is independent of the stimulatory effect of FSH on testicular protein synthesis.

Age Factors↗

PubMed1989

Analogues of alpha-aminoisobutyric acid with various alkyl groups as potential tumour imaging agents; effects of chain length on tumour and normal tissue specificity.

Eight 14C-labelled analogues of alpha-aminoisobutyric acid (AIB) were synthesized using the modified Bucherer technique to investigate their tissue distribution in Ehrlich tumour bearing mice. A structure-activity relationship within a series of AIB analogues was found; increasing the chain length of R and R' produced a progressive decrease in tumour and a dramatic decrease in normal tissue uptake. AIB and alpha-amino-2-methyl-butanoic acid (AMB) were found to have higher tumour uptake than the other six analogues; and AMB and alpha-amino-2-ethyl-butanoic acid (AEB) showed higher tumour to tissue uptake ratios than the other six analogues, significantly so for liver, stomach, heart, and small intestine. These results indicate that AMB may be a potential tumour seeking agent for emission computed tomography.

Aminobutyrates↗

PubMed1984

Synthesis and quality assurance of [11C]alpha-aminoisobutyric acid (AIB), a potential radiotracer for imaging and amino acid transport studies in normal and malignant tissues.

Carbon-11 labeled alpha-aminoisobutyric acid (AIB), a synthetic amino acid, was prepared by the modified Bucherer-Strecker amino acid synthesis from acetone, ammonium carbonate and [11C]KCN in the presence of carrier KCN. This method results in the labeling of AIB in the carboxyl group. The label is stable in this position because AIB is not a metabolized after cellular uptake. AIB is rapidly accumulated in viable cells including malignant cells. Since it is a non-metabolized amino acid, AIB offers the possibility of studying amino acid transport in vivo without interference by radiolabeled metabolic products. Radiochemical yields of [11C]AIB of 35-60% have been obtained in 70-80 min with radiopurities greater than 99%. Carrier added syntheses gave 15-25 mCi of [11C]AIB with specific activities of 0.3 Ci/mmol. Our quality control program which insures that [11C]AIB is suitable for imaging studies in patients with cancer includes HPLC analyses of product identity and purity, apyrogenecity and isotonicity assays, and a sensitive test for cyanide.

Aminobutyrates↗

PubMed1998

High-performance liquid chromatographic determination of beta-alanine, beta-aminoisobutyric acid and gamma-aminobutyric acid in tissue extracts and urine of normal and (aminooxy)acetate-treated rats.

A method is described for the simultaneous determination of beta-alanine, beta-aminoisobutyric acid and gamma-aminobutyric acid in biological materials. Amino acids including these beta- and gamma-amino acids were derivatized with 4-dimethylaminoazobenzene-4'-sulfonyl (dabsyl) chloride and dabsyl amino acids formed were separated by reversed-phase high-performance liquid chromatography. Dabsyl derivatives of these beta- and gamma-amino acids were well separated from other dabsyl-amino acids. The method was applied to the determination of these beta- and gamma-amino acids in trichloroacetic acid extracts of various tissues and to the urine of normal rats and those injected with (aminooxy)acetate (AOA). AOA injection (15 mg per kg of body mass) produced remarkable increase in beta-alanine contents in liver, kidney and urine (10.2, 4.6 and 25.7 times, respectively).

Aminoisobutyric Acids↗

PubMed1980

Tubular reabsorption of alpha-aminoisobutyric acid in the pre-steady-state. Evidence for a cell-to-lumen flux.

We investigated time-dependent and concentration-dependent renal handling of alpha-aminoisobutyric acid (AIB) in the rat during seven consecutive 30-min clearance periods after onset of AIB infusion. Following low-level rapid venous infusion of AIB (9.75 mumol/kg in 30 s), plasma [AIB] fell exponentially in the initial three periods and in linear fashion (-0.00158 microM/min) thereafter. Although filtered AIB fell in proportion to plasma [AIB] during the early clearance periods (5--125 min), fractional excretion of AIB (FEAIB) rose (delta FEAIB = + 0.077 +/- 0.010, mean +/- SD) and stabilized only in later clearance periods (125--215 min). Saturable intrarenal binding does not explain rising FEAIB with falling plasma [AIB] because sequential infusions of AIB, 120 min apart, also elicited the phenomenon after each infusion. During continuous infusions of AIB, time dependence of FEAIB was also observed, in the early interval (5--95 min), after onset of AIB infusion at various concentrations of plasma [AIB] below 3 mM approximately. Measurement of concentration-dependent net tubular reabsorption of AIB in the fourth through seventh clearance periods (near the steady state) revealed progressive saturation over the whole range of plasma [AIB] (0--12 mM), yet with a collapse of net reabsorption in the plasma [AIB] range 2--4 mM. Measurements of renal tissue AIB in these experiments revealed that cellular AIB is of sufficient magnitude and bears such a relationship to plasma AIB and FEAIB that it could contribute to an observable cell-to-lumen movement of amino acid in the "pre-steady-state" situation and could account for the rise in FEAIB following AIB infusion and the collapse in tubular reabsorption of AIB at 2--4 mM plasma [AIB].

Absorption↗

PubMed1991

Elevated urinary excretion of beta-aminoisobutyric acid and delta-aminolevulinic acid (ALA) and the inhibition of ALA-synthase and ALA-dehydratase activities in both liver and kidney in mice exposed to lead.

Urinary excretion of beta-aminoisobutyric acid (ABA) and delta-aminolevulinic acid (ALA) was investigated in mice exposed to lead (500 p.p.m.) in drinking water for 14 days. Concentrations of both urinary ABA and urinary ALA increased significantly in the lead-exposed mice. However, the degree of increasing excretion was higher in urinary ALA (10-fold of the control) than in urinary ABA (2-fold of the control). On the other hand, it was demonstrated that ALA dehydratase in liver and kidney is inhibited by exposure to lead, while ALA synthase in these tissues has no inhibitory effect.

5-Aminolevulinate Synthetase↗

PubMed1979

Inhibition of alpha-aminoisobutyric acid transport in membrane vesicles from mouse fibroblasts after phosphorylation by cyclic AMP-dependent protein kinase.

Cyclic AMP-dependent protein kinases from several mammalian sources inhibit Na+-dependent alpha-aminoisobutyric acid transport by membrane vesicles isolated from 3T3 cells. Evidence is provided that phosphorylation of membrane proteins by the enzyme is responsible for the inhibition. Lysis of the vesicles, or a reduction in the intravesicular volume is not the cause of reduced transport. The cyclic AMP-dependent protein kinase and its catalytic subunit phosphorylate a number of membrane proteins. Most of these proteins are phosphorylated, but to a lesser extent in the absence of protein kinase or cyclic AMP. The phosphorylated proteins remain associated with the membranes during hypotonic lysis treatments, which would be expected to release intravesicular contents and loosely associated membrane proteins. 32P-labeled bands detected on sodium dodecyl sulfate polyacrylamide gels after phosphorylation of membranes by the catalytic subunit of the cyclic AMP-dependent kinase are eliminated by treatment with either pronase or 1 N NaOH, but not by ribonuclease nor by phospholipase C. The stability of the incorporated radioactivity to hot acid and hydroxylamine relative to hot base suggests that most of the 32P from [gamma-32P]ATP is incorporated into protein phosphomonoester linkages.

Adenosine Triphosphate↗

PubMed1993

[Genetic dimorphism in beta-aminoisobutyric acid excretion in patients with atherosclerosis of the coronary artery and in groups at risk for atherosclerosis in the Lithuanian population].

Frequency of genetic variants of excretion of beta-aminoisobutyric acid (BAIB) in the urea was examined in patients suffering from atherosclerosis of coronary arteries and in risk group for atherosclerosis: children frequently suffering from respiratory viral infection, children with insulin-dependent diabetes mellitus (IDDM) and in adults suffering from IDDM and non-insulin-dependent diabetes mellitus. With the aim to determine whether excretion of BAIB could be related with CMV persistence of with proteolytic activity of blood serum the IgG class antibodies against CMV and level of alpha 1-proteinase inhibitor (alpha 1-PI) in blood serum was tested also. Frequency of high excretors of BAIB was found significantly more often (P < 0.01) in children suffering from virus infection compared to that of population. Frequency distribution of BAIB excretion showed that "high excretors" were found significantly more often in children suffering from atherosclerosis. The difference of BAIB excretion among healthy and diabetics was not defined (P > 0.05). The changes of excretion of BAIB in urea were not related with quantity of alpha 1-PI in blood serum. Investigation reveal a possible relation between high BAIB excretor and latent CMV infection and that this may impact atherogenesis. This leads to a suggestion that children who are often ill with respiratory virus infection may constitute a risk group for coronary atherosclerosis.

Adolescent↗

PubMed1986

Tumor imaging with carbon-11 labeled alpha-aminoisobutyric acid (AIB) in a patient with advanced malignant melanoma.

A 29 year-old-man presenting with advanced metastatic malignant melanoma was successfully imaged using carbon-11 (11C) labeled alpha-aminoisobutyric acid (AIB), a synthetic, non-metabolized amino acid transported into viable cells by the A-type, or alanine-preferring, amino acid transport system. Tumor located in the hilum of the lung was well visualized with 11C-AIB prior to chemotherapy. A gallium image with liver subtraction using 99mTc-sulfur colloid demonstrated regions of increased activity in liver which correlated with regions of increased activity on the 11C-AIB liver image.

Adult↗

PubMed1990

Excretion patterns of pseudouridine and beta-aminoisobutyric acid in patients with tumours of the upper urinary tract.

In 39 patients with either pelvic or renal cell tumours, the pre-operative urinary excretion ratios of pseudouridine/creatinine (psi:C) and beta-aminoisobutyric acid/creatinine (BAIB:C) were estimated. In 34/39 of the patients (87%), including both types of tumours, psi: C was found to be increased, and in only one patient was the value decreased. Twenty-five of the patients (64%) had a BAIB:C ratio within the normal range. 10 (25%) had increased and 4 (11%) decreased values. In 13 patients the psi:C and BAIB:C ratios from the affected side were compared with the values in urine from the bladder. Twelve of the patients had higher values of psi:C in the urine from the ureter. In seven patients the ureteric BAIB:C ratio was higher than the bladder BAIB:C ratio and in five patients the ureteric BAIB:C ratio was less than the bladder BAIB:C ratio. In only one patient were the values similar. The results indicate that patients with tumours of the upper urinary tract have changed excretion patterns compared with normal subjects and the urinary ratios on the affected side are different from those on the healthy side. The biological tumour markers pseudouridine and beta-aminoisobutyric acid may be helpful in the diagnosis of tumours in the upper urinary tract.

Adult↗

PubMed1989

Regional alterations in blood-to-brain transfer of alpha-aminoisobutyric acid and sucrose, after chronic administration and withdrawal of dexamethasone.

The effect of dexamethasone administration and withdrawal was studied with respect to blood-brain barrier function. The tracers alpha-[3H]aminoisobutyric acid (AIB) (MW 104) and [14C]sucrose (MW 342), which have a low permeability across the intact endothelium, were simultaneously injected intravenously in rats treated with dexamethasone and placebo-treated control animals or in rats in which dexamethasone treatment was discontinued 3 days before the experiment. Unidirectional transfer constants (Ki) were determined in discrete brain regions. Steroid administration reduced the rate of influx of AIB and sucrose, whereas discontinuation of drug resulted in an increased permeability. These findings suggest that when exposure to glucocorticoids is prolonged, the efficiency of medical treatment of CNS diseases may decrease due to reduction of drug delivery to CNS. Thus, these experimental findings may have particular importance in the clinical setting of drug administration when considering the combination of steroids with other drugs, and may aid in understanding better the pathogenesis of some types of brain edema seen in patients from whom corticosteroid therapy has been withdrawn.

Aminoisobutyric Acids↗

PubMed1993

Urinary N-acetyl-beta-D-glucosaminidase and beta-aminoisobutyric acid in workers occupationally exposed to metals such as chromium, nickel, and iron.

To examine the relationships between the urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) and beta-aminoisobutyric acid (AIBA) as a metabolite of thymine, and exposure to chromium, nickel, and iron, we determined these parameters in 58 workers engaged in the cutting and grinding of stainless steel or iron-steel plates. A significant increase in urinary NAG activity or urinary AIBA excretion was found in some of these workers. However, we could not find a significant positive correlation between the urinary excretion of NAG or AIBA and the urinary concentration of chromium, nickel, or iron as an indicator of internal dose.

Acetylglucosaminidase↗

PubMed1985

Stimulative effect of nerve growth factor on alpha-aminoisobutyric acid uptake and Na,K-ATPase activity in superior cervical sympathetic ganglia excised from adult rats.

Effects of nerve growth factor (NGF) on the uptake of non-metabolizable alpha-aminoisobutyric acid (AIB) and on Na,K-ATPase activity in superior cervical sympathetic ganglia (SCG) excised from adult rats were examined during aerobic incubation in vitro. Active uptake of labelled AIB into isolated SCG during 1 to 5 hours incubation at 37 degrees C was significantly accelerated by the addition of NGF to the incubation medium in a dose-dependent manner. Although the Km value of the AIB uptake by the SCG did not change with the addition of NGF, Vmax was nearly doubled. The NGF-evoked increase in AIB uptake was antagonized by the further addition of its specific antiserum in a dose-dependent fashion, and was largely suppressed in a medium containing ouabain. In SCG, axotomized one week prior to the examination, from which most of the neurons had disappeared and reactive proliferation of satellite glial components was in progress, the NGF-induced acceleration of AIB uptake was completely absent. The ganglionic Na,K-ATPase activity was greatly stimulated in the presence of NGF, and the effect was completely eliminated in the axotomized SCG. These results strongly suggest that the NGF-induced acceleration of active AIB uptake by the isolated SCG occurs not in glial cells but exclusively in the neuronal components with the apparent coupling of an Na ion extrusion process.

Aminoisobutyric Acids↗

PubMed1978

Anaerobic transport of serine and 2-aminoisobutyric acid by Staphylococcus epidermidis.

A membrane-bound ATPase detected in extracts of anaerobically grown Staphylococcus epidermidis was inhibited by a variety of compounds which inhibit ATPases in other organisms. Serine and 2-aminoisobutyric acid (AIB) were shown to enter the organism via the same transport system. The transport of AIB, the membrane potential and the transmembrane pH gradient were partially or completely abolished by the same inhibitors and also by uncoupling agents and lipid-soluble ions. It is proposed therefore that this ATPase generates and maintains an electrochemical gradient of protons across the cytoplasmic membrane of S. epidermidis capable of driving AIB uptake. Studies of AIB-induced proton movements suggested that AIB enters via a proton symport mechanism.

Adenosine Triphosphatases↗

PubMed1980

Further properties of sodium ion-stimulated alpha-[1-14C]aminoisobutyric acid uptake in alkalophilic Bacillus species.

Alkalophilic Bacillus No. 8-1 and No. 10A-2, isolated on alkaline media containing NaHCO3 and K2CO3, respectively, required Na+ specifically for the uptake of alpha-aminoisobutyric acid (AIB) into the cells. The K+ added to the uptake medium inhibited the accumulation of AIB in the cells of Bacillus No, 8-1, acting as a competitive inhibitor of the system. Sodium ion prevented the release of AIB from pre-loaded cells. Both potassium and lithium ions had the effect of retaining the AIB pool. The Vmax value for transport increased about five-fold when the pH value of medium was raised from 7 to 9, whereas the Km value decreased with the increase of concentration of sodium ion in the medium of pH 7 or 9. Sodium ion gradient across the membrane caused transient uptake by AIB by membrane vesicles of Bacillus No. 8-1.

Aminoisobutyric Acids↗

PubMed1984

Stimulation by somatomedin-C of aminoisobutyric acid uptake in human fibroblasts: a possible test for cellular responsiveness to somatomedin.

The effect of purified somatomedin-C (Sm-C)/insulin-like growth factor I on the uptake of alpha-aminoisobutyric acid (AIB) by confluent cultures of human fibroblasts was studied. An increase in [3H]AIB uptake was observed within 30 min of Sm-C addition, and a maximal effect was reached at 2.5 h (averaging 200% of control AIB uptake). Under the conditions employed, less Sm-C was required for maximal stimulation of [3H]AIB uptake (10 ng/ml in most cell lines) than for a maximal effect on [3H]thymidine incorporation (greater than 30 ng/ml). In multiple experiments with different lines of foreskin-derived and nongenital fibroblasts, the concentration of Sm-C resulting in half-maximal stimulation of [3H]AIB uptake was reproducible and was between 1.7 and 4.8 ng/ml in all cell lines tested except one. No significant difference was observed in the Sm responsiveness of cells from newborns and that of those from normal older children. Determination of binding of [125I]Sm-C to confluent monolayers of one fibroblast line revealed that the concentration of Sm-C resulting in half-maximal binding was nearly identical to that producing half-maximal [3H]AIB uptake stimulation. Stimulation of AIB uptake by an optimal concentration of epidermal growth factor (5 ng/ml) was also determined in several normal cell lines and was consistently close to 140% of the control value. Since epidermal growth factor and Sm interact with different receptors, this response may be a useful measure of cell integrity which is independent of the Sm receptor. The techniques for measurement of AIB uptake described in this report may prove useful in determining whether some children with growth failure of unknown etiology have target cell resistance to Sms.

Adolescent↗