Kinetics of Neutral Amino Acid Transport Across the Blood‐Brain Barrier
Abstract
Neutral amino acid (NAA) transport across the blood-brain barrier was examined in pentobarbital-anesthetized rats with an in situ brain perfusion technique. Fourteen of 16 plasma NAAs showed measurable affinity for the cerebrovascular NAA transport system. Values of the transport constants (Vmax, Km, KD) were determined for seven large NAAs from saturation studies, whereas Km values for five small NAAs were estimated from inhibition studies. These data, together with our previous work, provide a complete set of constants for prediction of NAA influx from plasma. Among the NAAs, Vmax varied at least fivefold and Km varied approximately 700 fold. The apparent affinity (1/Km) of each NAA was related linearly (r = 0.910) to the octanol/water partition coefficient, a measure of NAA side-chain hydrophobicity. Predicted influx values from transport constants and average plasma concentrations agree well with values measured using plasma perfusate. These results provide accurate new estimates of the kinetic constants that determine NAA transport across the blood-brain barrier. Furthermore, they suggest that affinity of a L-alpha-amino acid for the transport system is determined primarily by side-chain hydrophobicity.
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The influx of leucine exceeds that of all other large neutral amino acids.
“However, the influx of leucine exceeds that of all others (Smith et al., 1987;Yudkoff, 1997).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Smith et al., 1987
13C6-labeled leucine is an essential amino acid that rapidly crosses the blood-brain barrier via facilitative neutral amino acid transport.
“We chose 13 C6-labeled leucine because it is one of the essential amino acids that rapidly crosses the blood brain barrier via facilitative neutral amino acid transport [34].”
From Measurement of apolipoprotein E and amyloid β clearance rates in the mouse brain using bolus stable isotope labeling (2012) · cites this paper as [34]
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- Authors
- Smith, Q. R., Momma, S., Aoyagi, M., & Rapoport, S. I.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Smith, Quentin R.
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 1987-11
- Volume
- 49
- Issue
- 5
- Pages
- 1651-1658
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2081868313
- Cited by
- 454
- References
- 0
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 5 · 2023: 5 · 2022: 9 · 2021: 8 · 2020: 7 · 2019: 11 · 2018: 11 · 2017: 5 · 2016: 11 · 2015: 11 · 2014: 11 · 2013: 10 · 2012: 13
- FWCI
- 10.11
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- 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
- neutral amino acid transport, blood-brain barrier, transport kinetics, octanol-water partition coefficient, side chain hydrophobicity, in situ brain perfusion, plasma amino acids
- MeSH terms
- Amino Acids, Animals, Binding, Competitive, Biological Transport, Blood-Brain Barrier, Brain, Capillary Permeability, Cerebral Cortex, Kinetics, Male, Perfusion, Phenylalanine, Rats
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