Disease relevance of alpha-Methylalanine

• Thus, enhanced blood-brain transfer of alpha-aminoisobutyric acid preceded the development of overt hepatic encephalopathy [1].
• The transport of alpha-aminoisobutyric acid (AIB) by rat hepatoma tissue culture (HTC) cells is rapidly and reversibly inhibited by dexamethasone and other glucocorticoids [2].
• Role of Na+ in alpha-aminoisobutyric acid uptake by membrane vesicles from mouse fibroblasts transformed by simian virus 40 [3].
• Similarly, the detergent-induced loss of accumulated alpha-aminoisobutyric acid from Saccharomyces cerevisiae and of potassium from Escherichia coli is also strongly affected by the energy state of the cells [4].
• Capillary permeability, expressed in terms of a blood-to-tissue transfer constant (K), was determined in two rat brain tumor models by measuring the entry of 14C-alpha aminoisobutyric acid into brain tumor, into brain tissue adjacent to tumor, and into cortex [5].

High impact information on alpha-Methylalanine

• These same low concentrations of HOCl caused disturbance of various plasma membrane functions: they inactivated glucose and aminoisobutyric acid uptake, caused loss of cellular K+, and an increase in cell volume [6].
• In an attempt to stabilize ANF in vivo, a synthetic analogue of the hormone was prepared that contained the amino acid analogue, aminoisobutyric acid, substituted at position 13 [7].
• The basal rate of aminoisobutyric acid (AIB) uptake was increased in hepatocytes from both uremic and pair-fed control rats [8].
• CONCLUSIONS: Hepatocellular volume regulatory mechanisms and concentrative proline uptake are significantly impaired after cold preservation and rewarming, unlike alpha-aminoisobutyric acid and glutamine uptake [9].
• The increase in alpha-aminoisobutyric acid transfer within the gray-matter areas suggested that a general or nonspecific increase in brain capillary permeability occurred in these areas [1].

Chemical compound and disease context of alpha-Methylalanine

• Transport of alpha-aminoisobutyric acid and 2-deoxy-D-glucose in African green monkey kidney cells was measured 8 to 100 hr following permissive simian virus 40 infection [10].
• Ethylnitrosourea (ENU)-induced gliomas in rats have the lowest rate of blood-to-tissue transfer of the water-soluble compound alpha-aminoisobutyric acid of all experimental brain tumors studied to date [11].
• Imaging experimental brain tumors with 1-aminocyclopentane carboxylic acid and alpha-aminoisobutyric acid: comparison to fluorodeoxyglucose and diethylenetriaminepentaacetic acid in morphologically defined tumor regions [12].
• After 4 hours of ischemia, brain water content and blood-brain barrier permeability to [3H] alpha-aminoisobutyric acid and sodium-22 were determined [13].
• 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 [14].

Biological context of alpha-Methylalanine

• The increased uptake of alpha-aminoisobutyric acid at 11 and 18 h implies that the transfer of other solutes would also be enhanced, that central nervous system homeostasis would be compromised, and that the resulting changes in brain fluid composition could contribute to or cause hepatic encephalopathy [1].
• The simultaneous addition of NaSCN and alpha-aminoisobutyric acid to these vesicles produced a transient accumulation above the equilibrium level (overshoot, active transport) [15].
• The kinetics of transport of alpha-aminoisobutyric acid are shown to be biphasic both in whole cells and in the membrane vesicles [16].
• Lithium ion at concentrations between 2 and 20 mM simulated the stimulatory effects of insulin on the uptake of alpha-aminoisobutyric acid, synthesis of RNA and DNA, and cell multiplication in mouse mammary gland explants cultured in a chemically defined synthetic medium [17].
• The rate of transport of alpha-aminoisobutyric acid (AIB) has been measured in Swiss 3T3 cells at different cell densities in the range 10(3) to 5 x 10(4) cells/cm2 [18].

Anatomical context of alpha-Methylalanine

• Regulation of active alpha-aminoisobutyric acid transport expressed in membrane vesicles from mouse fibroblasts [19].
• In contrast, hyperosmotic blood-brain barrier disruption produced a large and significant increase in the transfer constant of alpha-aminoisobutyric acid in tumor-free cortex (from 0.002 +/- 0.001 to 0.05 +/- 0.011 mL/[g/min]) and in tumor-free corpus callosum (from 0.001 +/- 0.003 to 0.017 +/- 0.005 mL/[g/min]) [11].
• An in vitro model system employing cultured, adult, bovine aortic endothelial cells was used to study the mechanism of insulin stimulation of aminoisobutyric acid (AIB) uptake and the effects of low-density lipoprotein (LDL), malondialdehyde-altered LDL (MDA-LDL), and B-migrating very-low-density lipoprotein (B-VLDL) on this process [20].
• Dissociation of cell density and cell cycle effects on the rate of transport of alpha-aminoisobutyric acid in 3T3 cells [18].
• The endogenous 2-aminoisobutyric acid uptake rates in oocytes were sufficiently slow so as to provide a low background value that was subtracted to obtain transport rates for the mammalian carrier alone [21].

Associations of alpha-Methylalanine with other chemical compounds

• Ethanol (1.7 and 3.9 mg per ml) for 48 hr stimulated alpha-aminoisobutyric acid net uptake by fetal hepatocytes (p less than 0.05) [22].
• The hormonal responsiveness of the cells over the glucocorticoid-induced transition was assessed by the ability of insulin to stimulate the cellular uptake of 2-deoxyglucose and aminoisobutyric acid [23].
• Cycloleucine transport was a composite phenomenon involving at least two saturable processes, one of which was sodium-dependent and inhibited by alpha-aminoisobutyric acid, and probably represents entry through the A and ASC systems [24].
• Taking our data together, we conclude the following: (i) HER tyrosine kinase activity is required to elicit EGF stimulation of both 2-deoxyglucose and 2-aminoisobutyric acid uptake; (ii) mutations on individual HER autophosphorylation sites, Tyr-1068, Tyr-1148, and Tyr-1173 do not impair EGF-stimulated 2-deoxyglucose uptake [25].
• The percent accessible tissue space (distribution volume) and the permeability x capillary surface product for aminoisobutyric acid (M(r) 103), methotrexate (M(r) 454), dextran 10 (M(r) 10,000), and dextran 70 (M(r) 70,000) were measured between 8 and 16 days after inoculation of tumor [26].

Gene context of alpha-Methylalanine

• Parathyroid hormone (PTH)-(1-14) and -(1-11) analogs conformationally constrained by alpha-aminoisobutyric acid mediate full agonist responses via the juxtamembrane region of the PTH-1 receptor [27].
• Stimulation of [3H] aminoisobutyric acid uptake by insulin, epidermal growth factor (EGF), multiplication-stimulating activity, and somatomedin C (Sm-C) in Leprechaun cells was diminished relative to control cells at all concentrations tested [28].
• Glycine at position 12 (present in all homologues of PTH and in PTHrP), which is predicted in both hormones to participate in a beta-turn, was examined by substituting conformational reporters, such as D- or L-Ala, Pro, and alpha-aminoisobutyric acid (Aib), in both agonist and antagonist analogues [29].
• Of other proposed islet growth factors, cholecystokinin, epidermal growth factor, platelet-derived growth factor, and 2-aminoisobutyric acid, an increase in insulin secretion and islet cell proliferation was only observed with cholecystokinin in neonatal rat islets [30].
• Inhibition of pancreatic alpha-aminoisobutyric acid uptake by cholecystokinin and other secretagogues [31].

Analytical, diagnostic and therapeutic context of alpha-Methylalanine

• Symptomatic tumor-bearing rats were studied with double-label quantitative autoradiography to concurrently measure blood flow and a unidirectional blood-to-tissue transfer constant (K) for alpha-aminoisobutyric acid (AIB) [32].
• Pulse-labeling experiments with alpha-aminoisobutyric acid revealed that colchicine did not inhibit amino acid transport per se, but prevented the increased capacity for amino acid transport induced by partial hepatectomy [33].
• Solution conformations of the protected 2-9 segment of the peptaibol antibiotics emerimicins III and IV [alpha-aminoisobutyric acid (Aib)]3-L-Val-Gly-L-Leu-(Aib)2 and the related short sequences benzyloxy-(Aib)3-L-Val-OMe and benzyloxy-(Aib)3-L-Val-Gly-OMe have been investigated by circular dichroism studies [34].
• A comparison of Mab and alpha-aminoisobutyric acid influx constants suggests that Mab entry into intracerebral xenografts occurs through large pores without significant sieving or steric restriction [35].
• Ultra-low temperature techniques (microdissection and autoradiography) were used to study the nucleocytoplasmic distribution and transport of alpha-aminoisobutyric acid (AIB) in an amino acid-accumulating cell [36].

References