Glutamine transport by the blood-brain barrier: a possible mechanism for nitrogen removal
Abstract
Glutamine and glutamate transport activities were measured in isolated luminal and abluminal plasma membrane vesicles derived from bovine brain endothelial cells. Facilitative systems for glutamine and glutamate were almost exclusively located in luminal-enriched membranes. The facilitative glutamine carrier was neither sensitive to 2-aminobicyclo(2,2,1)heptane-2-carboxylic acid inhibition nor did it participate in accelerated amino acid exchange; it therefore appeared to be distinct from the neutral amino acid transport system L1. Two Na-dependent glutamine transporters were found in abluminal-enriched membranes: systems A and N. System N accounted for ∼80% of Na-dependent glutamine transport at 100 μM. Abluminal-enriched membranes showed Na-dependent glutamate transport activity. The presence of 1) Na-dependent carriers capable of pumping glutamine and glutamate from brain into endothelial cells, 2) glutaminase within endothelial cells to hydrolyze glutamine to glutamate and ammonia, and 3) facilitative carriers for glutamine and glutamate at the luminal membrane may provide a mechanism for removing nitrogen and nitrogen-rich amino acids from brain.
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Transporters of neutral and excitatory amino acids, glycine, taurine, and GABA are enriched abluminally and mediate high-affinity transport from brain to endothelium in a sodium-dependent fashion, after which these amino acids are transported across the luminal membrane into the blood via low-affinity transporters mediating clearance of nitrogen-rich and acidic amino acids into the circulation.
“Transporters of neutral and excitatory AA, glycine, taurine, and GABA are enriched abluminally and with high-affinity transport from brain-to-endothelium in a sodium-dependent fashion, and then, these AA are transported across the luminal membrane of the BBB into the blood via low-affinity transporters mediating AA clearance of nitrogen-rich and acidic AA into the circulation (351, 453).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [351]
Glutamine is transported into endothelium via sodium-coupled neutral amino acid transporters 1, 2, 3, and 5 (SNAT1/2/3/5), then hydrolyzed in endothelium to glutamate via glutaminase, and removed into circulation.
“Glutamine is transported into endothelium via sodium-coupled neutral AA transporter 1, 2, 3, and 5 (SNAT1/2/3/5) and then hydrolyzed in endothelium to glutamate via glutaminase, and removed into circulation (351).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [351]
Cites
Fine structural localization of glutamine synthetase in astrocytes of rat brain
Norenberg, M. D., & Martinez-Hernandez, A. (1979) · Brain Research · doi:10.1016/0006-8993(79)90071-4 · Cited by 1,349 · see citing works
Primary structure and functional characterization of a high-affinity glutamate transporter
Kanai, Y., & Hediger, M. A. (1992) · Nature · doi:10.1038/360467a0 · Cited by 1,339 · see citing works
Cloning and expression of a rat brain L-glutamate transporter
Pines, G., Danbolt, N. C., Bjørås, M., Zhang, Y., Bendahan, A., Eide, L., Koepsell, H., Storm‐Mathisen, J., Seeberg, E. C., & Kanner, B. I. (1992) · Nature · doi:10.1038/360464a0 · Cited by 1,232 · see citing works
Storck, T., Schulte, S., Hofmann, K., & Stoffel, W. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.22.10955 · Cited by 1,185 · see citing works
Biochemistry and physiology of brain ammonia.
Cooper, A. J. L., & Plum, F. (1987) · Physiological Reviews · doi:10.1152/physrev.1987.67.2.440 · Cited by 850 · see citing works
Distinct Mediating Systems for the Transport of Neutral Amino Acids by the Ehrlich Cell
Oxender, D. L., & Christensen, H. N. (1963) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)75327-7 · Cited by 834 · see citing works
Amino acid assignment to one of three blood-brain barrier amino acid carriers
Oldendorf, W., & Szabo, J. (1976) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1976.230.1.94 · Cited by 594 · see citing works
Kinetics of Neutral Amino Acid Transport Across the Blood‐Brain Barrier
Smith, Q. R., Momma, S., Aoyagi, M., & Rapoport, S. I. (1987) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1987.tb01039.x · Cited by 454 · see citing works
Kilberg, M. S., Handlogten, M. E., & Christensen, H. N. (1980) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)85625-9 · Cited by 428 · see citing works
James, J. H., Jeppsson, B. W., Ziparo, V., & Fischer, J. (1979) · The Lancet · doi:10.1016/s0140-6736(79)92119-6 · Cited by 414 · see citing works
The metabolic fate of 13N-labeled ammonia in rat brain.
Cooper, A. J. L., McDonald, J. M., Gelbard, A. S., Gledhill, R. F., & Duffy, T. E. (1979) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)50550-0 · Cited by 353 · see citing works
Curthoys, N. P., & Lowry, O. H. (1973) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)44458-x · Cited by 326 · see citing works
Shaw, P. J., Forrest, V., Ince, P. G., Richardson, J., & Wastell, H. (1995) · Neurodegeneration · doi:10.1006/neur.1995.0026 · Cited by 269 · see citing works
Castillo, J., Dávalos, A., Naveiro, J., & Noya, M. (1996) · Stroke · doi:10.1161/01.str.27.6.1060 · Cited by 258 · see citing works
Glutamine: A Key Substrate for the Splanchnic Bed
Souba, W. W. (1991) · Annual Review of Nutrition · doi:10.1146/annurev.nu.11.070191.001441 · Cited by 247 · see citing works
The Use of N-Methylation to Direct the Route of Mediated Transport of Amino Acids
Christensen, H. N., Oxender, D. L., Liang, M., & Vatz, K. A. (1965) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)97187-5 · Cited by 243 · see citing works
Regional distribution and extracellular levels of amino acids in rat central nervous system
Tossman, U., JONSSON, G., & Ungerstedt, U. (1986) · Acta Physiologica Scandinavica · doi:10.1111/j.1748-1716.1986.tb07938.x · Cited by 209 · see citing works
Recent Advances in Mammalian Amino Acid Transport
Kilberg, M. S., Stevens, B. R., & Novak, D. (1993) · Annual Review of Nutrition · doi:10.1146/annurev.nu.13.070193.001033 · Cited by 190 · see citing works
del Pino, M. M. S., Peterson, D. R., & Hawkins, R. A. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.25.14913 · Cited by 120 · see citing works
Self-citationCangiano, C., Cardelli‐Cangiano, P., James, J. H., Fanelli, F. R., Patrizi, M., Brackett, K. A., Ström, R., & Fischer, J. E. (1983) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)32149-5 · Cited by 110 · see citing works
[38] Distinguishing amino acid transport systems of a given cell or tissue
Christensen, H. N. (1989) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(89)73040-8 · Cited by 110 · see citing works
The identification of neutral amino acid transport systems
Barker, G., & Ellory, J. (1990) · Experimental Physiology · doi:10.1113/expphysiol.1990.sp003382 · Cited by 101 · see citing works
del Pino, M. M. S., Hawkins, R. A., & Peterson, D. R. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.25.14907 · Cited by 92 · see citing works
Self-citationCharacterization and distribution of the neuronal glutamate transporter EAAC1 in rat brain
Velaz-Faircloth, M., McGraw, T. S., alandro, M. S., Fremeau, R. T., Kilberg, M. S., & Anderson, K. J. (1996) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1996.270.1.c67 · Cited by 87 · see citing works
Ammonia selectively stimulates neutral amino acid transport across blood-brain barrier
Mans, A. M., Biebuyck, J. F., & Hawkins, R. A. (1983) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1983.245.1.c74 · Cited by 81 · see citing works
Self-citationLeighton, B., Curi, R., Hussein, A., & Newsholme, E. A. (1987) · FEBS Letters · doi:10.1016/0014-5793(87)81137-7 · Cited by 74 · see citing works
Neutral amino acid transport by the blood-brain barrier. Membrane vesicle studies.
del Pino, M. M. S., Hawkins, R. A., & Peterson, D. R. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)35701-6 · Cited by 73 · see citing works
Self-citationNet amino acid transport between plasma and erythrocytes and perfused dog brain.
Drewes, L. R., Conway, W. P., & Gilboe, D. (1977) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1977.233.4.e320 · Cited by 70 · see citing works
High-affinity transport of glutamate in rat brain microvessels
Hutchison, H. T., Eisenberg, H. M., & Haber, B. (1985) · Experimental Neurology · doi:10.1016/0014-4886(85)90216-x · Cited by 53 · see citing works
Hawkins, R. A., DeJoseph, M. R., & Hawkins, P. A. (1995) · Cell and Tissue Research · doi:10.1007/bf00583389 · Cited by 51 · see citing works
Self-citationSystem A-mediated amino acid transport: metabolic control at the plasma membrane
Kilberg, M. S. (1986) · Trends in Biochemical Sciences · doi:10.1016/0968-0004(86)90138-6 · Cited by 49 · see citing works
Characterization of amino acid transport in human endothelial cells
Bussolati, O., Sala, R., Astorri, A., Rotoli, B. M., Dall’Asta, V., & Gazzola, G. C. (1993) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1993.265.4.c1006 · Cited by 48 · see citing works
Glutamate is transported across the rat blood-brain barrier by a sodium-independent system
Benrabh, H., & Lefauconnier, J.-M. (1996) · Neuroscience Letters · doi:10.1016/0304-3940(96)12635-5 · Cited by 43 · see citing works
Characterization of glutamine transport by liver plasma membrane vesicles
Jacob, R., Rosenthal, N. R., & Barrett, E. J. (1986) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1986.251.5.e509 · Cited by 37 · see citing works
Glutamine transport in human skeletal muscle
Ahmed, A., Maxwell, D. L., Taylor, P. M., & Rennie, M. J. (1993) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1993.264.6.e993 · Cited by 32 · see citing works
Changes in brain metabolism in hepatic encephalopathy
Hawkins, R. A., Mans, A. M., & Biebuyck, J. F. (1987) · Neurochemical Pathology · doi:10.1007/bf02833600 · Cited by 31 · see citing works
Self-citationCharacterization of Na(+)-independent glutamine transport in rat liver
Pacitti, A. J., Inoue, Y., & Souba, W. W. (1993) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1993.265.1.g90 · Cited by 20 · see citing works
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Blood-Brain Barrier: From Physiology to Disease and Back
Sweeney, M. D., Zhao, Z., Montagne, A., Nelson, A. R., & Zlokovic, B. V. (2019) · Physiological Reviews · doi:10.1152/physrev.00050.2017 · Cited by 2,294 · see citing works
Quantitative flux analysis reveals folate-dependent NADPH production
Fan, J., Ye, J., Kamphorst, J. J., Shlomi, T., Thompson, C. B., & Rabinowitz, J. D. (2014) · Nature · doi:10.1038/nature13236 · Cited by 1,114 · see citing works
Munger, J. C., Bennett, B. D., Parikh, A., Feng, X., McArdle, J., RABITZ, H. A., Shenk, T. E., & Rabinowitz, J. D. (2008) · Nature Biotechnology · doi:10.1038/nbt.1500 · Cited by 630 · see citing works
Liu, X., Olszewski, K. L., Zhang, Y., Lim, E. W., Shi, J., Zhang, X., Zhang, J., Lee, H., Koppula, P., Lei, G., et al. (2020) · Nature Cell Biology · doi:10.1038/s41556-020-0496-x · Cited by 599 · see citing works
Fructose-1,6-bisphosphatase opposes renal carcinoma progression
Li, B., Qiu, B., Lee, D. S. M., Walton, Z. E., Ochocki, J. D., Mathew, L. K., Mancuso, A., Gade, T. P. F., Keith, B., Nissim, I., et al. (2014) · Nature · doi:10.1038/nature13557 · Cited by 535 · see citing works
Structural and functional aspects of the blood-brain barrier
Begley, D. J., & Brightman, M. (2003) · Birkhäuser Basel eBooks · doi:10.1007/978-3-0348-8049-7_2 · Cited by 452 · see citing works
Regulation of Amino Acid and Glucose Transporters in Endothelial and Smooth Muscle Cells
Mann, G. E., Yudilevich, D. L., & Sobrevia, L. (2003) · Physiological Reviews · doi:10.1152/physrev.00022.2002 · Cited by 430 · see citing works
Redzic, Z. B. (2011) · Fluids and Barriers of the CNS · doi:10.1186/2045-8118-8-3 · Cited by 128 · see citing works
Structure of the Blood–Brain Barrier and Its Role in the Transport of Amino Acids
Hawkins, R. A., O’Kane, R. L., Simpson, I. A., & Viña, J. R. (2006) · The Journal of Nutrition · doi:10.1093/jn/136.1.218s · Cited by 453 · see citing works
Self-citationTransport of Glutamate and Other Amino Acids at the Blood-Brain Barrier
Smith, Q. R. (2000) · Journal of Nutrition · doi:10.1093/jn/130.4.1016s · Cited by 381 · see citing works
Transcription factor NRF2 regulates miR-1 and miR-206 to drive tumorigenesis
Singh, A., Happel, C., Manna, S. K., Acquaah-Mensah, G., Carrerero, J., Kumar, S., Nasipuri, P., Krausz, K. W., Wakabayashi, N., Dewi, R., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci66353 · Cited by 333 · see citing works
Transfer of glutamine between astrocytes and neurons
Bröer, S., & Brookes, N. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00322.x · Cited by 325 · see citing works
The blood-brain barrier and glutamate.
Hawkins, R. (2009) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.2009.27462bb · Cited by 294 · see citing works
Self-citationHladky, S. B., & Barrand, M. A. (2016) · Fluids and Barriers of the CNS · doi:10.1186/s12987-016-0040-3 · Cited by 291 · see citing works
The genesis of cystic fibrosis lung disease
Wine, J. J. (1999) · Journal of Clinical Investigation · doi:10.1172/jci6222 · Cited by 275 · see citing works
Na+-dependent Glutamate Transporters (EAAT1, EAAT2, and EAAT3) of the Blood-Brain Barrier
O'Kane, R. L., Martı́nez-López, I., DeJoseph, M. R., Viña, J. R., & Hawkins, R. A. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.45.31891 · Cited by 268 · see citing works
Self-citationLangbein, S., Zerilli, M., Hausen, A. Z., Staiger, W., Rensch-Boschert, K., Lukán, N., Popa, J., Ternullo, M. P., Steidler, A., Weiss, C., et al. (2006) · British Journal of Cancer · doi:10.1038/sj.bjc.6602962 · Cited by 261 · see citing works
O-GlcNAcylation of G6PD promotes the pentose phosphate pathway and tumor growth
Rao, X., Duan, X., Mao, W., Li, X., Li, Z., Li, Q., Zheng, Z., Xu, H., Chen, M., Wang, P. G., et al. (2015) · Nature Communications · doi:10.1038/ncomms9468 · Cited by 259 · see citing works
Monocarboxylate transporter MCT1 is a target for immunosuppression
Murray, C. M., Hutchinson, R., Bantick, J. R., Belfield, G., Benjamin, A., Brazma, D., Bundick, R. V., Cook, I. D., Craggs, R. I., Edwards, S., et al. (2005) · Nature Chemical Biology · doi:10.1038/nchembio744 · Cited by 253 · see citing works
Free amino acid and dipeptide changes in the body fluids from Alzheimer’s disease subjects
Fonteh, A. N., Harrington, R. J., Tsai, A., Liao, P. S., & Harrington, M. G. (2006) · Amino Acids · doi:10.1007/s00726-006-0409-8 · Cited by 248 · see citing works
The Astroglial ASCT2 Amino Acid Transporter as a Mediator of Glutamine Efflux
Bröer, A., Brookes, N., Ganapathy, V., DIMMER, K.-S., Wagner, C. A., Lang, F. J. W., & Bröer, S. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.02184.x · Cited by 239 · see citing works
Nucleotide Release Provides a Mechanism for Airway Surface Liquid Homeostasis
Lazarowski, E. R., Tarran, R., Grubb, B. R., van Heusden, C. A., Okada, S. F., & Boucher, R. C. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m405367200 · Cited by 236 · see citing works
Physiology and pharmacological role of the blood-brain barrier.
Bernacki, J., Dobrowolska, A., Nierwińska, K., & Małecki, A. (2008) · PubMed · Cited by 234 · see citing works
Chudzik, A., Orzyłowska, A., Rola, R., & Stanisz, G. J. (2021) · Biomolecules · doi:10.3390/biom11071000 · Cited by 212 · see citing works
Mammoto, A., Huang, S., Moore, K. A., Oh, P., & Ingber, D. E. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m402725200 · Cited by 210 · see citing works
Transport of Amino Acids Across the Blood-Brain Barrier
Zaragozá, R. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.00973 · Cited by 202 · see citing works
Hladky, S. B., & Barrand, M. A. (2018) · Fluids and Barriers of the CNS · doi:10.1186/s12987-018-0113-6 · Cited by 206 · see citing works
Pries, A. R., & Kuebler, W. M. (2006) · Springer eBooks · doi:10.1007/3-540-32967-6_1 · Cited by 197 · see citing works
Lee, M. G., Choi, J. Y., Luo, X., Strickland, E., Thomas, P., & Muallem, S. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.21.14670 · Cited by 190 · see citing works
Boren, J., Cascante, M., Marín, S., Comı́n-Anduix, B., Centelles, J. J., Lim, S. K., Bassilian, S., Ahmed, S. M., Lee, W. P., & Boros, L. G. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m105796200 · Cited by 182 · see citing works
Self-citationPyruvate kinase type M2: a crossroad in the tumor metabolome
Mazurek, S., Grimm, H., Boschek, C. B., Vaupel, P. W., & EIGENBRODT, E. (2002) · British Journal Of Nutrition · doi:10.1079/bjn2001454 · Cited by 159 · see citing works
Expression of Large Amino Acid Transporter LAT1 in Rat Brain Endothelium
Duelli, R., Enerson, B. E., Gerhart, D. Z., & Drewes, L. R. (2000) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-200011000-00005 · Cited by 153 · see citing works
Glutamine as a mediator of ammonia neurotoxicity: A critical appraisal
Albrecht, J., Zielińska, M., & Norenberg, M. D. (2010) · Biochemical Pharmacology · doi:10.1016/j.bcp.2010.07.024 · Cited by 151 · see citing works
Glutamine: The Emperor or His Clothes?
Young, V. R., & Ajami, A. M. (2001) · Journal of Nutrition · doi:10.1093/jn/131.9.2449s · Cited by 150 · see citing works
Stimulation of Integrin-mediated Cell Contractility by Fibronectin Polymerization
Hocking, D. C., Sottile, J., & Langenbach, K. J. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.14.10673 · Cited by 140 · see citing works
NADPH Oxidase-dependent Acid Production in Airway Epithelial Cells
Schwarzer, C., Machen, T. E., Illek, B., & Fischer, H. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m404983200 · Cited by 140 · see citing works
Boulland, J., Osen, K. K., Levy, L. M., Danbolt, N. C., Edwards, R. H., Storm‐Mathisen, J., & Chaudhry, F. A. (2002) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2002.01995.x · Cited by 139 · see citing works
Teichberg, V. I., Malina, K. C.-K., Cooper, I., & Zlotnik, A. A. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.02.075 · Cited by 135 · see citing works
Glutamine efflux from astrocytes is mediated by multiple pathways
Deitmer, J. W., Bröer, A., & Bröer, S. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.01981.x · Cited by 135 · see citing works
Ramos‐Montoya, A., Lee, W. P., Bassilian, S., Lim, S. K., Trebukhina, R. V., Kazhyna, M. V., Ciudad, C. J., Noé, V., Centelles, J. J., & Cascante, M. (2006) · International Journal of Cancer · doi:10.1002/ijc.22227 · Cited by 135 · see citing works
Self-citationGlutamate: an amino acid of particular distinction.
Young, V. R., & Ajami, A. (2000) · Journal of NutriLife · doi:10.1093/jn/130.4.892s · Cited by 114 · see citing works
Yudkoff, M. (2016) · Neurochemical Research · doi:10.1007/s11064-016-2057-z · Cited by 130 · see citing works
Revisiting the blood-brain barrier: A hard nut to crack in the transportation of drug molecules
Harilal, S., Jose, J., Parambi, D. G. T., Kumar, R., Unnikrishnan, M. K., Uddin, M. S., Mathew, G. E., Pratap, R., Marathakam, A., & Mathew, B. (2020) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2020.03.018 · Cited by 124 · see citing works
Absent Secretion to Vasoactive Intestinal Peptide in Cystic Fibrosis Airway Glands
Joo, N. S., Irokawa, T., Wu, J. V., Robbins, R. C., Whyte, R. I., & Wine, J. J. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m208826200 · Cited by 120 · see citing works
Carnitine: transport and physiological functions in the brain
NACZ, K. (2004) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2004.06.001 · Cited by 115 · see citing works
Cationic amino acid transport across the blood-brain barrier is mediated exclusively by system y+
O’Kane, R. L., Vinã, J. R., Simpson, I. A., Zaragozá, R., Mokashi, A. S., & Hawkins, R. A. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00007.2006 · Cited by 109 · see citing works
Self-citationHashimoto, K., Engberg, G., Shimizu, E., Nordin, C., Lindström, L., & Iyo, M. (2005) · BMC Psychiatry · doi:10.1186/1471-244x-5-6 · Cited by 106 · see citing works
O'Kane, R. L., & Hawkins, R. A. (2003) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00193.2003 · Cited by 105 · see citing works
Self-citationComı́n-Anduix, B., Boros, L. G., Marín, S., Boren, J., Callol-Massot, C., Centelles, J. J., Torres, J. L., Agell, N., Bassilian, S., & Cascante, M. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m206150200 · Cited by 105 · see citing works
Metabolism of Amino Acids in the Brain and Their Roles in Regulating Food Intake
He, W., & Wu, G. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-45328-2_10 · Cited by 102 · see citing works
Garnett, J. P., Hickman, E. S., Burrows, R., Hegyi, P. J., Tiszlavicz, L., Cuthbert, A. W., Fong, P., & Gray, M. A. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.266734 · Cited by 101 · see citing works
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Adedoyin, A. A., & Ekenseair, A. K. (2018) · Nano Research · doi:10.1007/s12274-018-2198-2 · Cited by 98 · see citing works
Changes in the cellular distribution of glutamine synthetase in Alzheimer's disease
Robinson, S. R. (2001) · Journal of Neuroscience Research · doi:10.1002/jnr.10057 · Cited by 96 · see citing works
Tachikawa, M., & Hosoya, K. (2011) · Fluids and Barriers of the CNS · doi:10.1186/2045-8118-8-13 · Cited by 94 · see citing works
Role of collagenase in mediating in vitro alveolar epithelial wound repair
Planus, E., Galiacy, S. D., Matthay, M. A., Laurent, V., Gavrilović, J., Murphy, G., Clérici, C., Isabey, D., Lafuma, C., & d’Ortho, M. (1999) · Journal of Cell Science · doi:10.1242/jcs.112.2.243 · Cited by 93 · see citing works
The role of SLC transporters for brain health and disease
Nguyen, Y. T.-K., Ha, H. T. T., Nguyen, T. H., & Nguyen, L. N. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-04074-4 · Cited by 98 · see citing works
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Leibowitz, A., Boyko, M., Shapira, Y., & Zlotnik, A. A. (2012) · International Journal of Molecular Sciences · doi:10.3390/ijms130810041 · Cited by 92 · see citing works
Native Chemical Ligation at Glutamine
Siman, P., Karthikeyan, S. V., & Brik, A. (2012) · Organic Letters · doi:10.1021/ol300254y · Cited by 91 · see citing works
Cilingir, E. K., Seven, E. S., Zhou, Y., Walters, B. M., Mintz, K. J., Pandey, R. R., Wikramanayake, A. H., Chusuei, C. C., Vanni, S., Graham, R. M., et al. (2021) · Journal of Colloid and Interface Science · doi:10.1016/j.jcis.2021.02.058 · Cited by 90 · see citing works
Rhythmic glucose metabolism regulates the redox circadian clockwork in human red blood cells
Ch, R., Rey, G., Ray, S., Jha, P. K., Driscoll, P. C., dos Santos, M. S., Malik, D. M., Lach, R., Weljie, A. M., MacRae, J. I., et al. (2021) · Nature Communications · doi:10.1038/s41467-020-20479-4 · Cited by 88 · see citing works
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Henry-Unaeze, H. N. (2017) · Pathophysiology · doi:10.1016/j.pathophys.2017.08.001 · Cited by 85 · see citing works
Lee, W.-N. P., Guo, P., Lim, S., Bassilian, S., Lee, S. T., Boren, J., Cascante, M., Go, V. L. W., & Boros, L. G. (2004) · British Journal of Cancer · doi:10.1038/sj.bjc.6602243 · Cited by 83 · see citing works
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Sonnay, S., Gruetter, R., & Duarte, J. M. N. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00288 · Cited by 74 · see citing works
REVIEW: Small Bowel Review: Normal Physiology Part 1
Thomson, A. B. R., Keelan, M., Thiesen, A., Clandinin, M. T., Ropeleski, M. J., & Wild, G. (2001) · Digestive Diseases and Sciences · doi:10.1023/a:1012794505897 · Cited by 75 · see citing works
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Bachmann, C., Braissant, O., Villard, A.-M., Boulat, O., & Henry, H. (2004) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2003.10.014 · Cited by 70 · see citing works
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Zhang, G., Sadhukhan, S., Tochtrop, G. P., & Brunengraber, H. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.r110.171405 · Cited by 70 · see citing works
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Nałęcz, K. A. (2016) · Neurochemical Research · doi:10.1007/s11064-016-2030-x · Cited by 69 · see citing works
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Sharoni, Y., Danilenko, M., & Levy, J. (2000) · Drug Development Research · doi:10.1002/1098-2299(200007/08)50:3/4 · Cited by 45 · see citing works
Melone, M. (2004) · Cerebral Cortex · doi:10.1093/cercor/bhh018 · Cited by 68 · see citing works
Effects of sleep restriction on the human plasma metabolome
Bell, L. N., Kilkus, J. M., Booth, J. N., Bromley, L. E., Imperial, J. G., & Penev, P. D. (2013) · Physiology & Behavior · doi:10.1016/j.physbeh.2013.08.007 · Cited by 67 · see citing works
Li, X., Chlan‐Fourney, J., Juorio, A. V., Bennett, V. L., Shrikhande, S., Keegan, D. L., Jin, Q., & Boulton, A. A. (1999) · Journal of Neuroscience Research · doi:10.1002/(sici)1097-4547(19990401)56:1 · Cited by 57 · see citing works
Boros, L. G., Lapis, K., Szende, B., Tömösközi‐Farkas, R., Balogh, Á., Boren, J., Marín, S., Cascante, M., & Hídvégi, M. (2001) · Pancreas · doi:10.1097/00006676-200108000-00004 · Cited by 67 · see citing works
Poustforoosh, A., Nematollahi, M., Hashemipour, H., & Pardakhty, A. (2022) · Journal of Controlled Release · doi:10.1016/j.jconrel.2022.02.015 · Cited by 46 · see citing works
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Malina, K. C.-K., Cooper, I., & Teichberg, V. I. (2011) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2011.121 · Cited by 62 · see citing works
Gaube, F., Wölfl, S., Pusch, L., Kroll, T. C., & Hamburger, M. O. (2007) · BMC Pharmacology · doi:10.1186/1471-2210-7-11 · Cited by 62 · see citing works
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Lanz, B., Rolf Gruetter, A., & Duarte, J. M. N. (2013) · Frontiers in Endocrinology · doi:10.3389/fendo.2013.00156 · Cited by 58 · see citing works
Bai, W., & Zhou, Y. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00400 · Cited by 57 · see citing works
Kundu, M., Saha, S., & Roy, M. N. (2017) · Journal of Molecular Liquids · doi:10.1016/j.molliq.2017.05.123 · Cited by 56 · see citing works
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Lai, W., Du, D., & Chen, L. (2022) · Neurochemical Research · doi:10.1007/s11064-021-03510-y · Cited by 55 · see citing works
O’Kane, R. L., Vinã, J. R., Simpson, I. A., & Hawkins, R. A. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00187.2004 · Cited by 54 · see citing works
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Elizondo-Vega, R. J., Recabal, A., & Oyarce, K. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00244 · Cited by 51 · see citing works
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Conway, M. E., & Hutson, S. M. (2016) · Advances in Neurobiology · doi:10.1007/978-3-319-45096-4_5 · Cited by 53 · see citing works
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Self-citationIsmahan, L., Leila, N., Fatiha, M., Guendouzi, A., Mouna, C., Nada, B., & Brahim, H. (2020) · Journal of Molecular Structure · doi:10.1016/j.molstruc.2020.127740 · Cited by 49 · see citing works
Dai, S.-S., Wang, H., Yang, N., An, J.-H., Li, W., Ning, Y., Zhu, P.-F., Chen, J., & Zhou, Y. (2013) · The Journal of Experimental Medicine · doi:10.1084/jem.20122196 · Cited by 48 · see citing works
Glutamine transport at the blood–brain and blood–cerebrospinal fluid barriers
Xiang, J., Ennis, S. R., Abdelkarim, G. E., Fujisawa, M., Kawai, N., & Keep, R. F. (2003) · Neurochemistry International · doi:10.1016/s0197-0186(03)00013-5 · Cited by 48 · see citing works
Boros, L., Lerner, M. R., Morgan, D. L., Taylor, S. L., Smith, B. J., Postier, R. G., & Brackett, D. J. (2005) · Pancreas · doi:10.1097/01.mpa.0000186524.53253.fb · Cited by 48 · see citing works
Onaolapo, O. J., Aremu, O. S., & Onaolapo, A. Y. (2017) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-017-1371-6 · Cited by 47 · see citing works
Glufosinate binds N-methyl-d-aspartate receptors and increases neuronal network activity in vitro
Lantz, S. R., Mack, C. M., Wallace, K., Key, E. F., Shafer, T. J., & Casida, J. E. (2014) · NeuroToxicology · doi:10.1016/j.neuro.2014.09.003 · Cited by 41 · see citing works
Nutritional support in hepatic encephalopathy
Mizock, B. A. (1999) · Nutrition · doi:10.1016/s0899-9007(98)00191-9 · Cited by 40 · see citing works
Bashir, B., Alam, S., Khandale, N. B., Birla, D., Vishwas, S., Pandey, N. K., Gupta, G., Paudel, K. R., Dureja, H., Kumar, P., et al. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102236 · Cited by 39 · see citing works
Interactions in inclusion complex of β-cyclodextrin/l-Metheonine: DFT computational studies
Nora, M., Ismahan, L., Guendouzi, A., Mouna, C., Leila, N., Fatiha, M., Nada, B., & Brahim, H. (2019) · Journal of Inclusion Phenomena and Macrocyclic Chemistry · doi:10.1007/s10847-019-00948-0 · Cited by 38 · see citing works
Ouattara, D. A., Prot, J. M., Bunescu, A., Dumas, M., Elena‐Herrmann, B., Leclerc, É., & Brochot, C. (2012) · Molecular BioSystems · doi:10.1039/c2mb25049g · Cited by 37 · see citing works
de Carvalho, A. S. R., Torres, L. B., Persike, D. S., Fernandes, M. J. D. S., Amado, D., Naffah‐Mazzacoratti, M. D. G., Cavalheiro, É. A., & da Silva, A. V. (2010) · Neurochemistry International · doi:10.1016/j.neuint.2010.12.014 · Cited by 36 · see citing works
- Authors
- Lee, W.-J., Hawkins, R. A., Viña, J. R., & Peterson, D. R.
- Affiliations
- Department of Physiology and Biophysics, Finch University of Health Science/The Chicago Medical School, North Chicago, Illinois 60064-3095; and
- Departamento de Bioquı́mica y Biologı́a Molecular, Facultades de Medicina y Farmacia, Universitat de Valencia, Valencia 46010, Spain
- ORCID
- Hawkins, Richard A.
- Venue
- American Journal of Physiology-Cell Physiology
- Publisher
- American Physiological Society
- Published
- 1998-04-01
- Volume
- 274
- Issue
- 4
- Pages
- C1101-C1107
- ISSN
- 0363-6143 (ISSN-L)
- 1522-1563
- OpenAlex
- W2243408637
- Cited by
- 191
- References
- 37
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 5 · 2023: 2 · 2022: 5 · 2021: 14 · 2020: 7 · 2019: 7 · 2018: 4 · 2017: 9 · 2016: 6 · 2015: 3 · 2014: 7 · 2013: 6 · 2012: 6
- FWCI
- 5.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Cell Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ns031017-03, 5r01ns016389-15)
- National Institute of Neurological Disorders and Stroke (NS-31017, NS16389)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Keywords
- glutamine transport, blood-brain barrier, glutamate uptake, brain endothelial cells, nitrogen removal, glutaminase, sodium-dependent transport, plasma membrane vesicles, system N, system A, ammonia removal, amino acid substitutions
- MeSH terms
- Animals, Biological Transport, Blood-Brain Barrier, Brain, Cattle, Cell Membrane, Endothelium, Vascular, Glutaminase, Glutamine, Nitrogen, Sodium, Glutamic Acid
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