Tyrosine • The body makes tyrosine from another amino acid called phenylalanine.• Tyrosine can also be found in dairy products, meats, fish, eggs, oats, and wheat,

chicken, turkey, milk, yogurt, cottage cheese, cheese, peanuts, almonds, pumpkin seeds, sesame seeds, soy products, lima beans, avocados, and bananas.

• People take tyrosine for:– depression– attention deficit disorder (ADD)– attention deficit-hyperactivity disorder (ADHD)– the inability to stay awake (narcolepsy) and improving alertness following sleep deprivation– premenstrual syndrome (PMS) – Parkinson's disease– Alzheimer's disease – chronic fatigue syndrome (CFS)– alcohol and cocaine withdrawal – heart disease and stroke– Erectile dysfunction – loss of interest in sex– Schizophrenia– appetite suppressant– Skin to reduce age-related wrinkles

• Dementia. Early research suggests that taking a combination of tyrosine, 5-hydroxytryptophan (5-HTP), and carbidopa (PO) does not improve symptoms in people with severe dementia due to Alzheimer's disease or multi-infarct dementia.• Schizophrenia.Early research suggests that taking L-tyrosine along with the drug molindone for 3 weeks does not improve symptoms of schizophrenia better than molindone alone.

• Levodopa interacts with TYROSINETyrosine might decrease how much levodopa the body absorbs. By decreasing how much levodopa the body absorbs, tyrosine might decrease the effectiveness of levodopa. Do not take tyrosine and levodopa at the same time.

• Thyroid hormone interacts with TYROSINEThe body naturally produces thyroid hormones. Tyrosine might increase how much thyroid hormone the body produces. Taking tyrosine with thyroid hormone pills might cause there to be too much thyroid hormone. This could increase the effects and side effects of thyroid hormones.

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

• 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.

• 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.

• Apart from their roles as constituents of protein, the only other known functions of the aromatic amino acids in brain are as precursors for the monoamine neurotransmitters, serotonin and the catecholamines [dopamine (DA),

norepinephrine (NE), and epinephrine]. This latter biochemical link is of interest, because the rates of synthesis and release of these transmitters are directly modified by the brain concentrations of their amino acid precursors, tryptophan (5HT) and phenylalanine (Phe) and tyrosine (Tyr; catecholamines), which in turn are influenced by their availability from blood. As a result, physiologic and pathophysiologic factors that influence blood concentrations of these amino acids and others that compete with them for a common transporter across the blood brain barrier [the large neutral amino acids (LNAA)] predictably alter aromatic amino acid concentrations in brain, the formation and release of these monoamine transmitters, and consequently brain function .

• Consideration will be given to the role of Phe in catecholamine synthesis in support of the idea that this amino acid functions as a cosubstrate with Tyr for Tyr hydroxylase (TH) and is not an inhibitor of this enzyme in vivo at normal and even high concentrations.

Tyr availability affects catecholamine synthesis rate

• Catecholamines are synthesized from Tyr The initial step involves hydroxylation to dihydroxyphenylalanine (DOPA), catalyzed by the enzyme TH. Once formed, DOPA is rapidly decarboxylated to DA by aromatic L-amino acid decarboxylase. In neurons that use DA as a transmitter, no further enzymatic modification occurs. Neurons that use NE as a transmitter contain an additional enzyme, DA-β-hydroxylase, that converts DA to NE. Neurons using epinephrine as a transmitter contain 1 additional enzyme, phenylethanolamine-N-methyl transferase, which is responsible for catalyzing the conversion of NE to epinephrine. The initial step in the pathway, Tyr hydroxylation, is rate limiting and thus controls the rate of synthesis through the entire pathway. Early work established that this enzyme was subject to end-product inhibition (by any of the above products) as examined either in vitro using enzyme preparations or in vivo, such as by following the rate of 14C-Tyr conversion to 14C-catecholamine in the brains of rats treated with a drug to raise endogenous catecholamine concentrations (e.g. a monoamine oxidase inhibitor) . Later work established that TH was subject to a number of other controls, including a rapid phosphorylation-linked activation of enzyme during periods of increased neuronal activity (i.e. synthesis increases at times of greater neuronal demand).

Brain Tyr uptake and DA and NE synthesis in neurons.

John D. Fernstrom, and Madelyn H. Fernstrom J. Nutr. 2007;137:1539S-1547S

©2007 by American Society for Nutrition

• The idea that precursor (Tyr) concentrations might directly influence the rate of Tyr hydroxylation and catecholamine production did not seem promising, because published values for the substrate Km were below normal brain Tyr concentrations [i.e. the enzyme was thought to be close to substrate saturation; see (2)]. However, a study then demonstrated that raising brain Tyr concentrations (by injecting the amino acid) could rapidly stimulate DOPA synthesis in rat brain (7). This finding suggested that Tyr concentrations in the vicinity of TH must be well below saturation levels. A subsequent refinement of this observation was that at least in DA neurons neuronal activation was required to observe a precursor-linked stimulation of DA synthesis. For example, Tyr administration could stimulate DA synthesis in the corpus striatum (the site of a major projection of terminals from DA cell bodies in the substantia nigra), but pretreatment of animals with a DA receptor antagonist to activate the neurons was required (8). A physiological demonstration of the requirement for neuronal activation is supplied by DA neurons in the rat retina. The retina contains a population of DA interneurons that is light sensitive; they are relatively inactive in darkness and become active in the light. In association with neuronal activation is an activation of TH (9). If activation is normally required for Tyr administration to stimulate Tyr hydroxylation rate, then Tyr injection should enhance hydroxylation rate in retinas during the day but not during night.