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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.
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“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
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“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
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“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
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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
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