L-tyrosine does not change malate dehydrogenase in the hippocampal (1.0-4.0 mM) or posterior cortex (0.1-4.0 mM), and it suppresses citrate synthase activity in the latter two regions (2.0 and 4.0 mM). elevated levels of striatum (4.0 mM), liver (0.1-4.0 mM), and succinate dehydrogenase. Analysis of complex I activity revealed suppression in the hippocampal region (4.0 mM). Complex II has inhibitory effects not just in the hippocampus but also in the liver (1.0, 2.0, and 4.0 mM) and posterior cortex (0.1-4.0 mM). L-tyrosine administration results in decreased activity of complex IV in the posterior brain (1.0-4.0 mM) and no change in the activity of complexes II–III[1].

L-tyrosine administered acutely reduced the activity of citrate synthase in the liver and posterior cortex but enhanced it in the striatum. The findings also shown that in the rat liver and posterior cortex, acute treatment of L-Tyrosine decreased the activity of complexes II, III, and IV of the mitochondrial respiratory chain and malate dehydrogenase. The striatum showed an increase in complex I and succinate dehydrogenase activity, while the posterior cortex showed an inhibition. Moreover, acute L-tyrosine treatment does not change the hippocampal energy metabolism [1].

Absorption, Distribution and Excretion
L-tyrosine is absorbed from the small intestine via a sodium-dependent active transport process. Semi-chronic exposure to aflatoxin B1 at non-toxic doses in male ICR mice leads to elevated lung tryptophan levels, while serotonin or 5-hydroxyindole-3-acetic acid levels remain unchanged. This change is organ-specific; tryptophan levels in the spleen, duodenum, heart, or central nervous system are not altered. Acute (48-hour) flunixin treatment reduces lung tryptophan levels and reverses the aflatoxin B1-mediated increase in lung tryptophan levels. Conversely, flunixin treatment reduces central nervous system tryptophan levels in control mice but has no such effect in aflatoxin B1-treated mice. Spleen serotonin levels are increased in aflatoxin B1-treated mice. Acute (48-hour) treatment with E. coli lipopolysaccharide (LPS) in mice increased serotonin levels in the spleen. Aflatoxin B1 treatment followed by LPS had a slight additive effect on serotonin levels in the spleen. LPS treatment increased serotonin levels in the mouse heart, but this effect was not affected by aflatoxin B1 pretreatment. Both LPS and aflatoxin B1 treatment alone increased tyrosine levels in lung tissue, but the combined treatment showed no significant difference compared to the control group. Flunixin treatment increased tyrosine levels in lung tissue, but aflatoxin B1 pretreatment did not affect this effect. Acute treatment with either LPS or flunixin decreased the tryptophan/tyrosine ratio in the central nervous system; aflatoxin B1 pretreatment prevented this change. Aflatoxin B1 pretreatment decreased catecholamine levels in the central nervous system of mice. However, in mice treated with aflatoxin B1, changes in central nervous system catecholamines could be restored to normal by vitamin E supplementation during treatment. Male Wistar rats were randomly assigned to either a heavy alcohol consumption group (daily ethanol intake exceeding 3.5 g/kg) or a light alcohol consumption group (daily ethanol intake less than 2.0 g/kg). Both groups were then administered 25% ethanol by gavage (8–11 g/kg/day) for 30 days. Results showed increased permeability of the blood-brain barrier to 14(C)-tyrosine, 14(C)-tryptophan, and 14(C)-DOPA at all stages of alcohol poisoning. All these changes were more pronounced in the light alcohol consumption group than in the heavy alcohol consumption group. Disulfiram, as well as milder doses of benzylazepam and diazepam, exacerbated the effects when co-administered with ethanol (for 16–30 days). The effects of mercuric chloride (100 μM), p-chloromercuric benzenesulfonate (1 μM), and oxobenzoarsine (250 μM) on: (a) the activity of the sodium pump in the gut of intact winter flounder; (b) the activity of sodium-potassium ATPase in tissue homogenates; and (c) sodium-dependent and sodium-independent uptake of tyrosine in brush border membrane vesicles were determined. All three reagents reduced cellular potassium concentration, but their effect on cellular potassium lagged behind their inhibition of ATPase. At the concentrations used in the using chamber (or one-tenth of the concentration), all reagents completely inhibited sodium-potassium ATPase activity in tissue homogenate enzyme activity assays. Conversely, only mercuric chloride reduced sodium-dependent uptake of tyrosine from brush border membrane vesicles. These results suggest that the effects of mercury and arsine on tyrosine uptake are due to the inhibition of sodium-potassium ATPase, thereby reducing the driving force of cellular uptake of sodium-tyrosine cotransport systems. The inhibitory effect of mercuric chloride may be related to its direct influence on sodium tyrosine cotransport, but not to chloromercuric benzenesulfonate or oxobenzoarsine.
In female Sprague-Dawley rats, brain levels of tryptophan, serotonin, and tyrosine were measured after acute (12-hour) intraperitoneal injection of aflatoxin B1 (100 μg/kg) or a solvent (10% acetone dissolved in 0.9% sodium chloride solution). In rats treated with aflatoxin B1, tyrosine levels were decreased in the brainstem, but not in the cerebellum or cortex. Acute aflatoxin B1 treatment led to increased tryptophan levels in all three brain regions (cerebrum, cerebellum, and cortex), while serotonin levels in the cerebellum and cortex remained unchanged, and serotonin levels in the brainstem decreased. These experiments indicate that the effects of acute aflatoxin B1 treatment on brain amino acids and serotonin are differential, and that changes in brain tryptophan (a precursor to serotonin) do not parallel changes in brain serotonin. For more complete data on the absorption, distribution, and excretion of L-tyrosine (10 in total), please visit the HSDB record page. Metabolism/Metabolites In the liver, L-tyrosine participates in a variety of biochemical reactions, including protein synthesis and oxidative catabolism. L-tyrosine not metabolized in the liver is distributed to various tissues of the body via systemic circulation. /Metabolic pathways of L-tyrosine:/ /Tyrosine synthesis/ p-Hydroxyphenylpyruvic acid to carbon dioxide + Homocyanin to maleoacetoacetate to fumaroacetoacetate to fumarate + acetoacetate; Tyrosine to 3,4-dihydroxyphenylalanine to carbon dioxide + 3,4-dihydroxyphenylethylamine to norepinephrine to epinephrine. L-Tyrosine is converted into N-acetyl-L-tyrosine in the human body; into 3-carboxy-L-tyrosine in mignonette; into p-coumaric acid in sugarcane; into p-cresol in Proteus; into 3,4-dihydroxy-L-phenylalanine in hamsters; into 3,4-dihydroxystilbene-2-carboxylic acid in hydrangeas; into 2,7-dimethylnaphthoquinone in silverleaf chrysanthemums; into L-dityrosine in beef; into p-hydroxymandelinni in sorghum; into p-hydroxyphenylacetal oxime in violets; and into p-hydroxyphenylpyruvic acid in rats. Beef contains 3-iodo-L-tyrosine; L-tyrosine produces ranunculin in Ranunculaceae plants; ranunculine in Ranunculaceae plants; mesbourin in Ashwagandha plants; navidin in Narcissus; neomycin in Streptomyces; phenol in rats; β-tocopherol in Anabaena; tylofrarin in Tylofra; tyramine in rats; β-tyrosine in Bacillus; L-tyrosine hydroxyxamic acid in beef; L-tyrosine-4-phosphate in Drosophila; and flavomycin in Penicillium. /Excerpt from table/
After 10 months of chronic alcohol poisoning with 10% ethanol, tyrosine metabolism in rats was impaired. In the initial 3-4 months, tyrosine aminotransferase activity in liver tissue was increased, while phenylalanine hydroxylase activity was decreased. During prolonged alcohol poisoning, tyrosine aminotransferase activity did not increase. However, within 5-6 months, tyrosine aminotransferase activity decreased, occurring concurrently with an increase in phenylalanine hydroxylase activity. In the early stages of alcohol poisoning, alcohol dehydrogenase activity in rat liver tissue also increased. From 3-4 months after alcohol poisoning, this enzyme activity gradually decreased and remained at a low level. High temperatures exacerbated these changes in rats with chronic alcohol poisoning. This study used a computer pattern recognition system to analyze spontaneous behaviors in rats after acute oral administration of high doses of aspartame, phenylalanine, or tyrosine. Male Sprague Dawley rats (250-300 g) were orally administered aspartame (500 or 100 mg/kg), phenylalanine (281 or 562 mg/kg), or tyrosine (309 or 618 mg/kg), and their behavior was analyzed one hour after administration. The computer pattern recognition system recorded and categorized 13 different behaviors exhibited by the animals in the first 15 minutes of exploring a new environment. These doses of aspartame, phenylalanine, and tyrosine did not induce significant changes in spontaneous behavior. Unlike low-dose amphetamine, despite high plasma concentrations of phenylalanine and tyrosine, no behavioral changes were detected by the computer pattern recognition system. For more complete metabolite/metabolite data on L-tyrosine (7 metabolites), please visit the HSDB record page. In the liver, L-tyrosine is involved in a variety of biochemical reactions, including protein synthesis and oxidative catabolism. L-tyrosine not metabolized in the liver is distributed to various tissues of the body via systemic circulation.

Toxicity Summary
Tyrosine is produced intracellularly from the hydroxylation of the essential amino acid phenylalanine. This relationship is very similar to that between cysteine and methionine. Half of the required phenylalanine is used for tyrosine production; if the diet is rich in tyrosine itself, the requirement for phenylalanine is reduced by about 50%. The antidepressant activity of L-tyrosine can be attributed to its precursor role in the synthesis of the neurotransmitters norepinephrine and dopamine. Elevated levels of norepinephrine and dopamine in the brain are thought to be associated with its antidepressant effects. Toxicity Data
LD50 (oral, rat) > 5110 mg/kg

[1]. Effect of L-tyrosine in vitro and in vivo on energy metabolism parameters in brain and liver of young rats. Neurotox Res. 2013 May;23(4):327-35.

Pharmacodynamics
Tyrosine is a non-essential amino acid synthesized in the body from phenylalanine. Tyrosine is crucial for the production of proteins, enzymes, and muscle tissue in the human body. It is a precursor to the neurotransmitters norepinephrine and dopamine. It can improve mood and has antidepressant effects. It may improve memory and enhance mental alertness. Tyrosine contributes to melanin production and plays a key role in the production of thyroxine (thyroid hormones). Tyrosine deficiency manifests as hypothyroidism, low blood pressure, and hypothermia. Tyrosine supplementation has been used to reduce stress, combat narcolepsy, and chronic fatigue.

C9H11NO3

181.1885

181.073

60-18-4

25619-78-7

6057

White to off-white solid powder

1.3±0.1 g/cm3

385.2±32.0 °C at 760 mmHg

>300 °C (dec.)(lit.)

186.7±25.1 °C

0.0±0.9 mmHg at 25°C

1.614

0.38

3

4

3

13

176

1

C1=CC(=CC=C1C[C@@H](C(=O)O)N)O

OUYCCCASQSFEME-QMMMGPOBSA-N

InChI=1S/C9H11NO3/c10-8(9(12)13)5-6-1-3-7(11)4-2-6/h1-4,8,11H,5,10H2,(H,12,13)/t8-/m0/s1

(2S)-2-amino-3-(4-hydroxyphenyl)propanoic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

1M HCl : 50 mg/mL (~275.95 mM)
DMSO : ~1 mg/mL (~5.52 mM)

Solubility in Formulation 1: 40 mg/mL (220.76 mM) in 50% PEG300 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication (<60°C).
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: 40 mg/mL (220.76 mM) in 0.5% CMC-Na/saline water (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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 (Please use freshly prepared in vivo formulations for optimal results.)