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Cited by 453Barrier Structure and Function StudiesAmino Acid Enzymes and MetabolismDrug Transport and Resistance Mechanisms

Structure of the Blood–Brain Barrier and Its Role in the Transport of Amino Acids

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Hawkins, Richard A, O’Kane, Robyn L, Simpson, Ian A, Viña, Juan R·2006·The Journal of Nutrition
DOI 10.1093/jn/136.1.218s
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Abstract

Brain capillary endothelial cells form the blood-brain barrier (BBB). They are connected by extensive tight junctions, and are polarized into luminal (blood-facing) and abluminal (brain-facing) plasma membrane domains. The polar distribution of transport proteins mediates amino acid (AA) homeostasis in the brain. The existence of two facilitative transporters for neutral amino acids (NAAs) on both membranes provides the brain access to essential AAs. Four Na(+)-dependent transporters of NAA exist in the abluminal membranes of the BBB. Together these systems have the capability to actively transfer every naturally occurring NAA from the extracellular fluid (ECF) to endothelial cells and from there into circulation. The presence of Na(+)-dependent carriers on the abluminal membrane provides a mechanism by which NAA concentrations in the ECF of brain are maintained at approximately 10% those of the plasma. Also present on the abluminal membrane are at least three Na(+)-dependent systems transporting acidic AAs (EAAT) and a Na(+)-dependent system transporting glutamine (N). Facilitative carriers for glutamine and glutamate are found only in the luminal membrane of the BBB. This organization promotes the net removal of acidic- and nitrogen-rich AAs from the brain and accounts for the low level of glutamate penetration into the central nervous system. The presence of a gamma-glutamyl cycle at the luminal membrane and Na(+)-dependent AA transporters at the abluminal membrane may ser…

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  • Sodium-dependent amino acid transporters ASCT1/2 and GLYT1 at the abluminal membrane remove nonessential amino acids alanine, serine, and cysteine, and glycine, respectively, from brain to blood.

    “Sodium-dependent AA transporters ASCT1/2 and GLYT1 at the abluminal membrane remove nonessential AA alanine, serine and cysteine, and glycine, respectively, from brainto-blood (240).”

    From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [240]

  • Glutamine levels are higher in brain interstitial fluid.

    “Glutamine levels are higher in brain ISF (240).”

    From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [240]

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Authors
Hawkins, R. A., O’Kane, R. L., Simpson, I. A., & Viña, J. R.
Affiliations
  • Universitat de València (ES)
  • LaGuardia Community College (US)
  • Pennsylvania State University (US)
Corresponding author
Hawkins, Richard A
ORCID
Venue
The Journal of Nutrition
Publisher
Elsevier BV
Published
2006-01
Volume
136
Issue
1
Pages
218S-226S
ISSN
0022-3166 (ISSN-L)
DOI
10.1093/jn/136.1.218s
OpenAlex
W2129219544
Cited by
453
References
3
Citations by year
2026: 12 · 2025: 16 · 2024: 16 · 2023: 21 · 2022: 23 · 2021: 28 · 2020: 32 · 2019: 26 · 2018: 26 · 2017: 28 · 2016: 23 · 2015: 31 · 2014: 21 · 2013: 18 · 2012: 27
FWCI
11.56
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Nutrition (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01ns031017-03)
  • Instituto de Salud Carlos III
  • National Institute of Neurological Disorders and Stroke (NS-31017, R01NS041405, NS-041405)
Topics
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Keywords
blood-brain barrier, amino acid transport, brain microvascular endothelial cells, tight junctions, endothelial cell polarity, neutral amino acid transporter, glutamate uptake, glutamine transport, glutamine synthetase, gamma-glutamyl cycle, pyroglutamic acid, amino acid homeostasis, essential amino acids
MeSH terms
Amino Acids, Ammonia, Animals, Biological Transport, Blood-Brain Barrier, gamma-Glutamyltransferase, Glutamine, Humans, Pyrrolidonecarboxylic Acid, Sodium, Glutamic Acid

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