Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The glutamine/amino acid transporter was solubilized from rat renal apical plasma membrane (brush-border membrane) with C12E8 and reconstituted into liposomes by removing the detergent from mixed micelles by hydrophobic chromatography on Amberlite XAD-4. The reconstitution was optimised with respect to the protein concentration, the detergent/phospholipid ratio and the number of passages through a single Amberlite column. The reconstituted glutamine/amino acid transporter catalysed a first-order antiport reaction stimulated by external, not internal, Na+. Optimal activity was found at pH 7.0. The sulfhydryl reagents HgCl2, mersalyl and p-hydroxymercuribenzoate and the amino acids alanine, serine, threonine, cysteine, asparagine, methionine and valine strongly inhibited the transport, whereas the amino acid analogue methylaminoisobutyrate had no effect. Glutamine, alanine, serine, asparagine, threonine were efficiently translocated from outside to inside and from inside to outside the proteoliposomes as well. Cysteine and valine were translocated preferentially from outside to inside. The Km for glutamine on the external and internal side of the transporter was 0.47 and 11 mM, respectively; the values were not influenced by the type of the counter substrate. The transporter is functionally asymmetrical and it is unidirectionally inserted into the proteoliposomal membrane with an orientation corresponding to that of the native membrane. By a bisubstrate kinetic analysis of the glutamine antiport, a random simultaneous mechanism was found. The glutamine antiport was strongly stimulated by internal nucleoside triphosphates and, to a lower extent, by pyrophoshate. The reconstituted glutamine/amino acid transporter functionally corresponds to the ASCT2 protein.
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PMID:Reconstitution into liposomes of the glutamine/amino acid transporter from renal cell plasma membrane: functional characterization, kinetics and activation by nucleotides. 1558 47

Transglutaminases (TGs) are calcium-dependent enzymes that catalyze the transamidation of glutamine residues of a protein substrate to form intermolecular isopeptide bonds. The zona pellucida (ZP) is an extracellular, glycoprotein matrix that surrounds the oocytes of all Eutherian mammals. We aimed to identify the immunoreactivity of tissue transglutaminase (tTG) and ultrastructural changes occuring in rat oocytes before and after fertilization. Female rats were stimulated to superovulate, then mated with males. Oocytes and embryos were collected and examined by immunohistochemistry and electron microscopy. Before fertilization, tTG was present only in the oolemma and the cortical cytoplasm. After fertilization, tTG reactivity increased in the ZP of the early zygote and the preimplantation embryos, but decreased in the cytoplasm and perivitelline space (PVS). After fertilization, the PVS ultrastructure became asymmetrical and large around the polar bodies with many cortical granule contents. In conclusion, tTG immunoreactivity was found to be spatially and temporarily heterogeneous in the rat oocytes and embryos, especially in the ZP.
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PMID:The distribution of transglutaminase in the rat oocytes and embryos. 1768 10

AMPA receptors (AMPA-Rs) are formed as heterotetrameric combinations of subunits known as GluR1-GluR4. The calcium permeability of AMPA-Rs is controlled by the identity of the amino-acid side chain contributed by each subunit at a key position in the conductance pathway, which can be either a glutamine (Q) or an arginine (R). Tetramers assembled only from Q-containing subunits are calcium permeable. In contrast, tetramers that incorporate R-containing subunits are calcium impermeable. Both forms play key roles in physiological and pathophysiological processes in the central nervous system. Here, using electron microscopy, we present the first quaternary structure of a calcium-permeable Q-homomeric AMPA-R. The receptor is elongated, with overall 2-fold symmetry and a large central vestibule. It is thus similar to the structure previously reported for an AMPA-R assembled exclusively from R-subunits. Both structures differ from those reported for brain-derived but urea-washed "native" AMPA-Rs, which exhibited multiple asymmetrical conformations. However, even transient exposure of our Q-homomeric AMPA-Rs to urea significantly attenuates the binding of a conformationally specific antibody. As a result, we propose a model in which all AMPA-Rs share a 2-fold symmetrical structure and in which subunit-dependent differences in assembly, trafficking, and electrophysiology are mediated within the framework of fundamentally similar quaternary conformations.
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PMID:The quaternary structure of a calcium-permeable AMPA receptor: conservation of shape and symmetry across functionally distinct subunit assemblies. 1865 86

The factors that explain the diverse arrangement of the major arteries of tetrapods are not known. Here, I aim to illuminate some of the underpinnings of these patterns. I review the variation in the sauropsid left, right, and dorsal aortae regarding the origin of the gastrointestinal blood vessels and the relative diameters of left and right aortae where they join together to form the dorsal aorta. I focus on these features because the quality of blood that flows through these aortae can vary depending on the state of cardiac shunting and the size of the vessel can provide insight into the quantity of blood borne by the vessels. I then place the information in a phyletic, historical, and ecological context. The plesiomorphic pattern is for the gastrointestinal vessels to arise as segmental arteries from the dorsal aorta, which is formed from the confluence of left and right aortae with similar diameters. The pattern is well conserved with only two major variations. First, in several clades of reptiles (testudines, crocodilians, lizards of the genera Varanus and Hydrosaurus) a substantial portion of the gastrointestinal arteries arises from the left aorta, leaving the diameter of the left aorta smaller than the right at their confluence. I hypothesize that this vascular arrangement facilitates growth by allowing more alkaline blood to flow to the somatic (body wall) and appendicular circulations, which may promote bone deposition and inhibit resorption, whereas hypercapnic, acidic blood flows to the digestive viscera, which may provide CO(2) as a substrate for the synthesis of gastric acid, bicarbonate, fatty acids, glutamine, purine rings, as well as glucose from lactate. Second, in some snakes and lizards with snake-like body forms, such as Amphisbaenidae, the diameters of left and right aortae are asymmetrical at their confluence with the left aorta exceeding the right, but in members of the amphibian order Gymnophiona the right generally exceeds the left. This condition is associated with asymmetrical development of the lungs.
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PMID:On the evolution of arterial vascular patterns of tetrapods. 2171 Jun 54

Caenorhabditis elegans NRF (NF-E2-related factor)/CNC (Cap'n'collar) transcription factor, Skinhead-1 (SKN-1), is conservatively critical for promoting phase II detoxification gene expressions in response to oxidative stress. SKN-1 activity is controlled by well-known phosphorylation and recently-reported O-GlcNAcylation. Whether other kinds of posttanslational modifications of SKN-1 occur and influence its function remains elusive. Here, we found arginines 484 and 516 (R484/R516) of SKN-1 were asymmetrically dimethylated by PRMT-1. Oxidative stress enhanced the binding of PRMT-1 to SKN-1. Consequently, asymmetrical dimethylation of arginines on SKN-1 was elevated. Loss of prmt-1 or disruption of R484/R516 dimethylation decreased the enrichment of SKN-1 on the promoters of SKN-1-driven phase II detoxification genes, including gamma-glutamine cysteine synthetase gcs-1, glutathione S-transferases gst-7 and gst-4, which resulted in reduced ability of worms to defense against oxidative stress. These findings have important implications for investigating the physiological and pathological functions of arginine methylation on conserved NRF/CNC transcription factors in human diseases related to oxidative stress response.
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PMID:Arginine methylation of SKN-1 promotes oxidative stress resistance in Caenorhabditis elegans. 3068 7

Systemic hypoxia-ischemia (HI) often occurs during preterm birth in human. HI induces injuries to hinder brain cells mainly in the ipsilateral forebrain structures. Such HI injuries may cause lifelong disturbances in the distant regions, such as the contralateral side of the cerebellum. We aimed to evaluate behavior associated with the cerebellum, to acquire cerebellar abundant metabolic alterations using in vivo 1H magnetic resonance spectroscopy (1H MRS), and to determine GFAP, NeuN, and MBP protein expression in the left cerebellum, in adult rats after mild early postnatal HI on the right forebrain at day 3 (PND3). From PND45, HI animals exhibited increased locomotion in the open field while there is neither asymmetrical forelimb use nor coordination deficits in the motor tasks. Despite the fact that metabolic differences between two cerebellar hemispheres were noticeable, a global increase in glutamine of HI rats was observed and became significant in the left cerebellum compared to the sham-operated group. Furthermore, increases in glutamate, glycine, the sum of glutamate and glutamine and total choline, only occurred in the left cerebellum of HI rats. Remarkably, there were decreased expression of MBP and NeuN but no detectable reactive astrogliosis in the contralateral side of the cerebellum of HI rats. Taken together, the detected alterations observed in the left cerebellum of HI rats may reflect disequilibrium in the glutamate-glutamine cycle and a delay in the return of glutamine from astrocytes to neurons from hypoxic-ischemic origin. Our data provides in vivo evidence of long-term changes in the corresponding cerebellum following mild neonatal HI in very immature rats, supporting the notion that systemic HI could cause cell death in the cerebellum, a distant region from the expected injury site.
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PMID:Mild Neonatal Brain Hypoxia-Ischemia in Very Immature Rats Causes Long-Term Behavioral and Cerebellar Abnormalities at Adulthood. 3123 Dec 32


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