1: J Nutr. 2007 Jun;137(6 Suppl 1):1539S-1547S; discussion 1548S.

Tyrosine, phenylalanine, and catecholamine synthesis and function in the brain.

Fernstrom JD, Fernstrom MH.

Department of Psychiatry, University of Pittsburgh School of Medicine,
Pittsburgh, PA 15213, USA. fernstromjd@upmc.edu

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.

PMID: 17513421 [PubMed - indexed for MEDLINE]