The DOI matches its Crossref record; 60 of the 60 references it cites were found in a registry or an index.
Tyrosine, Phenylalanine, and Catecholamine Synthesis and Function in the Brain2
Open accessAbstract
Aromatic amino acids in the brain function as precursors for the monoamine neurotransmitters serotonin (substrate tryptophan) and the catecholamines [dopamine, norepinephrine, epinephrine; substrate tyrosine (Tyr)]. Unlike almost all other neurotransmitter biosynthetic pathways, the rates of synthesis of serotonin and catecholamines in the brain are sensitive to local substrate concentrations, particularly in the ranges normally found in vivo. As a consequence, physiologic factors that influence brain pools of these amino acids, notably diet, influence their rates of conversion to neurotransmitter products, with functional consequences. This review focuses on Tyr and phenylalanine (Phe). Elevating brain Tyr concentrations stimulates catecholamine production, an effect exclusive to actively firing neurons. Increasing the amount of protein ingested, acutely (single meal) or chronically (intake over several days), raises brain Tyr concentrations and stimulates catecholamine synthesis. Phe, like Tyr, is a substrate for Tyr hydroxylase, the enzyme catalyzing the rate-limiting step in catecholamine synthesis. Tyr is the preferred substrate; consequently, unless Tyr concentrations are abnormally low, variations in Phe concentration do not affect catecholamine synthesis. Unlike Tyr, Phe does not demonstrate substrate inhibition. Hence, high concentrations of Phe do not inhibit catecholamine synthesis and probably are not responsible for the low production of catecholamines in subjects with phenylketonuria. Whereas neuronal catecholamine release varies directly with Tyr-induced changes in catecholamine synthesis, and brain functions linked pharmacologically to catecholamine neurons are predictably altered, the physiologic functions that utilize the link between Tyr supply and catecholamine synthesis/release are presently unknown. An attractive candidate is the passive monitoring of protein intake to influence protein-seeking behavior.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“As stated in the Introduction, the catecholamine depletion hypothesis proposes that tyrosine can exert beneficial effects when brain catecholamine levels are low and there is more room for tyrosine to be converted into L-DOPA, which then gets converted into dopamine and norepinephrine (Fernstrom and Fernstrom, 2007;O'Brien et al., 2007;Colzato et al., 2013).”
From Behavioral and cognitive effects of tyrosine intake in healthy human adults (2015) · cites this paper as Fernstrom and Fernstrom, 2007
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“The amino acid tyrosine is the precursor to the catecholamine neurotransmitters dopamine and norepinephrine.”
From Behavioral and cognitive effects of tyrosine intake in healthy human adults (2015) · cites this paper as Fernstrom and Fernstrom, 2007
In the citing paper
“Should the levels of the BCAA decrease then uptake of the aromatic amino acids would exceed that of BCAAs, increasing the synthesis of serotonin and dopamine (Fernstrom and Fernstrom 2007; Scarna et al. 2005).”
From Alzheimer’s disease: Targeting the glutamatergic system (2020) · cites this paper as Fernstrom and Fernstrom 2007
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Nagatsu, T., Levitt, M., & Udenfriend, S. (1964) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)93832-9 · Cited by 2,067
Brain metabolism: a perspective from the blood-brain barrier
Pardridge, W. M. (1983) · Physiological Reviews · doi:10.1152/physrev.1983.63.4.1481 · Cited by 745
PC12 Pheochromocytoma Cultures in Neurobiological Research
Greene, L. A., & Tischler, A. S. (1982) · Advances in cellular neurobiology · doi:10.1016/b978-0-12-008303-9.50016-5 · Cited by 725
Carlsson, A., Davis, J. N., Kehr, W., Lindqvist, M., & Atack, C. (1972) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/bf00508904 · Cited by 646
Branched-Chain Amino Acids and Brain Function
Fernstrom, J. D. (2005) · The Journal of Nutrition · doi:10.1093/jn/135.6.1539s · Cited by 514
Self-citationUdenfriend, S. (1966) · Pharmacological Reviews · doi:10.1016/s0031-6997(25)07173-x · Cited by 503
Role of precursor availability in control of monoamine biosynthesis in brain.
Fernstrom, J. D. (1983) · Physiological Reviews · doi:10.1152/physrev.1983.63.2.484 · Cited by 491
Self-citationNEUTRAL AMINO ACIDS IN THE BRAIN: CHANGES IN RESPONSE TO FOOD INGESTION1
Fernstrom, J. D., & Faller, D. V. (1978) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1978.tb10489.x · Cited by 425
Self-citationLight Stimulates Tyrosine Hydroxylase Activity and Dopamine Synthesis in Retinal Amacrine Neurons
Iuvone, P. M., Galli, C. L., Garrison-Gund, C. K., & Neff, N. H. (1978) · Science · doi:10.1126/science.30997 · Cited by 416
Solubilization and Partial Purification of Tyrosine Hydroxylase from Bovine Adrenal Medulla
Shiman, R., Akino, M., & Kaufman, S. (1971) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)76979-8 · Cited by 411
Cited by
Sorted by citations
The Shikimate Pathway and Aromatic Amino Acid Biosynthesis in Plants
Maeda, H. A., & Dudareva, N. (2012) · Annual Review of Plant Biology · doi:10.1146/annurev-arplant-042811-105439 · Cited by 1,568
A laser-engraved wearable sensor for sensitive detection of uric acid and tyrosine in sweat
Yang, Y., Song, Y., Bo, X., Min, J., Pak, O. S., Zhu, L., Wang, M., Tu, J., Kogan, A., Zhang, H., et al. (2020) · Nature Biotechnology · doi:10.1038/s41587-019-0321-x · Cited by 1,270
Dopamine: Functions, Signaling, and Association with Neurological Diseases
Klein, M. O., Battagello, D. S., Cardoso, A. R., Hauser, D. N., Bittencourt, J. C., & Correa, R. G. (2019) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-018-0632-3 · Cited by 1,073
A wearable electrochemical biosensor for the monitoring of metabolites and nutrients
Wang, M., Yang, Y., Min, J., Song, Y., Tu, J., Mukasa, D., Ye, C., Xu, C., Heflin, N., McCune, J. S., et al. (2022) · Nature Biomedical Engineering · doi:10.1038/s41551-022-00916-z · Cited by 957
Ding, J., Huang, Y., Liu, S., Zhang, S., Zou, H., Wang, Z., Zhu, W., & Geng, J. (2020) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2020.122693 · Cited by 278
Metadata
- Authors
- Fernstrom, J. D., & Fernstrom, M. H.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Fernstrom, John D.
- Venue
- The Journal of Nutrition
- Publisher
- Elsevier BV
- Published
- 2007-06
- Volume
- 137
- Issue
- 6
- Pages
- 1539S-1547S
- ISSN
- 0022-3166 (ISSN-L)
- OpenAlex
- W2169887727
- Cited by
- 755
- References
- 59
- Citations by year
- 2026: 68 · 2025: 88 · 2024: 84 · 2023: 64 · 2022: 65 · 2021: 64 · 2020: 51 · 2019: 32 · 2018: 28 · 2017: 34 · 2016: 30 · 2015: 24 · 2014: 26 · 2013: 22 · 2012: 10
- FWCI
- 0.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01hd024730-11)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD24730)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- tyrosine, phenylalanine, catecholamine synthesis, substrate inhibition, tyrosine hydroxylase, phenylketonuria, protein intake, dietary protein, serotonin, dopamine, norepinephrine, epinephrine, neurotransmitter synthesis, catecholamine release
- MeSH terms
- Animals, Brain, Catecholamines, Dihydroxyphenylalanine, Hydroxylation, Kinetics, Phenylalanine, Retina, Tyrosine, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
