General Information of MET (ID: META00182)
Name Tyrosine
Synonyms   Click to Show/Hide Synonyms of This Metabolite
(-)-a-Amino-p-hydroxyhydrocinnamate; (-)-a-Amino-p-hydroxyhydrocinnamic acid; (-)-alpha-Amino-p-hydroxyhydrocinnamic acid; (2S)-2-Amino-3-(4-hydroxyphenyl)propanoate; (2S)-2-Amino-3-(4-hydroxyphenyl)propanoic acid; (S)-(-)-Tyrosine; (S)-2-Amino-3-(p-hydroxyphenyl)propionate; (S)-2-Amino-3-(p-hydroxyphenyl)propionic acid; (S)-3-(p-Hydroxyphenyl)alanine; (S)-Tyrosine; (S)-a-Amino-4-hydroxy-benzenepropanoate; (S)-a-Amino-4-hydroxy-benzenepropanoic acid; (S)-a-Amino-4-hydroxybenzenepropanoate; (S)-a-Amino-4-hydroxybenzenepropanoic acid; (S)-alpha-Amino-4-hydroxy-benzenepropanoate; (S)-alpha-Amino-4-hydroxy-benzenepropanoic acid; (S)-alpha-Amino-4-hydroxybenzenepropanoic acid; 2-Amino-3-(4-hydroxyphen yl)-2-amino-3-(4-hydroxyphenyl)-propanoate; 2-Amino-3-(4-hydroxyphen yl)-2-amino-3-(4-hydroxyphenyl)-propanoic acid; 3-(4-Hydroxyphenyl)-L-alanine; 4-Hydroxy-L-phenylalanine; Benzenepropanoate; Benzenepropanoic acid; L Tyrosine; L-Tyrosin; L-p-Tyrosine; Para tyrosine; Para-tyrosine; TYROSINE; Tyr; Tyrosine, L isomer; Tyrosine, L-isomer; Y; p-Tyrosine
Source Aromatic homomonocyclic compounds
Structure Type   Amino acids, peptides, and analogues  (Click to Show/Hide the Complete Structure Type Hierarchy)
Organic acids and derivatives
Carboxylic acids and derivatives
Amino acids, peptides, and analogues
PubChem CID
6057
HMDB ID
HMDB0000158
Formula
C9H11NO3
Structure
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3D MOL 2D MOL
  Click to Show/Hide the Molecular/Functional Data (External Links/Property/Function) of This Metabolite
KEGG ID
C00082
DrugBank ID
DB00135
ChEBI ID
17895
FooDB ID
FDB000446
ChemSpider ID
5833
METLIN ID
34
Physicochemical Properties Molecular Weight 181.19 Topological Polar Surface Area 83.6
XlogP -2.3 Complexity 176
Heavy Atom Count 13 Rotatable Bond Count 3
Hydrogen Bond Donor Count 3 Hydrogen Bond Acceptor Count 4
Function
Tyrosine is an essential amino acid that readily passes the blood-brain barrier. Once in the brain, it is a precursor for the neurotransmitters dopamine, norepinephrine and epinephrine, better known as adrenalin. These neurotransmitters are an important part of the body's sympathetic nervous system, and their concentrations in the body and brain are directly dependent upon dietary tyrosine. Tyrosine is not found in large concentrations throughout the body, probably because it is rapidly metabolized. Folic acid, copper and vitamin C are cofactor nutrients of these reactions. Tyrosine is also the precursor for hormones, thyroid, catecholestrogens and the major human pigment, melanin. Tyrosine is an important amino acid in many proteins, peptides and even enkephalins, the body's natural pain reliever. Valine and other branched amino acids, and possibly tryptophan and phenylalanine may reduce tyrosine absorption. A number of genetic errors of tyrosine metabolism occur, such as hawkinsinuria and tyrosinemia I. Most common is the increased amount of tyrosine in the blood of premature infants, which is marked by decreased motor activity, lethargy and poor feeding. Infection and intellectual deficits may occur. Vitamin C supplements reverse the disease. Some adults also develop elevated tyrosine in their blood. This indicates a need for more vitamin C. More tyrosine is needed under stress, and tyrosine supplements prevent the stress-induced depletion of norepinephrine and can cure biochemical depression. However, tyrosine may not be good for psychosis. Many antipsychotic medications apparently function by inhibiting tyrosine metabolism. L-dopa, which is directly used in Parkinson's, is made from tyrosine. Tyrosine, the nutrient, can be used as an adjunct in the treatment of Parkinson's. Peripheral metabolism of tyrosine necessitates large doses of tyrosine, however, compared to L-dopa (http://www.dcnutrition.com).
Regulatory Network
Full List of Protein(s) Regulated by This Metabolite
      GPCR OA (GPCR-OA)
            G-protein coupled receptor 143 (GPR143) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Tyrosine decrease (12 hours)
                      Induced Change GPR143 protein expression levels: increase (FC = 5)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Albinism [ICD-11: EC23]
                      Details It is reported that tyrosine decrease causes the increase of GPR143 protein expression compared with control group.
Full List of Protein(s) Regulating This Metabolite
      Amino acid/auxin permease (AAAP)
            Sodium-coupled neutral amino acid transporter 9 (SLC38A9) Click to Show/Hide the Full List of Regulating Pair(s):   2 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair (1) Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Truncation of SLC38A9
                      Induced Change Tyrosine concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that truncation of SLC38A9 leads to the increase of tyrosine levels compared with control group.
               Regulating Pair (2) Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Overexpression of SLC38A9
                      Induced Change Tyrosine concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that overexpression of SLC38A9 leads to the decrease of tyrosine levels compared with control group.
            Solute carrier family 38 member 2 (SLC38A2) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [3]
                      Introduced Variation Knockdown (siRNA) of SLC38A2
                      Induced Change Tyrosine concentration: increase (FC = 1.52)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that knockdown of SLC38A2 leads to the increase of tyrosine levels compared with control group.
            Solute carrier family 38 member 3 (SLC38A3) Click to Show/Hide the Full List of Regulating Pair(s):   2 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair (1) Experim Info click to show the details of experiment for validating this pair [4]
                      Introduced Variation Knockout of Slc38a3
                      Induced Change Tyrosine concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that knockout of Slc38a3 leads to the decrease of tyrosine levels compared with control group.
               Regulating Pair (2) Experim Info click to show the details of experiment for validating this pair [4]
                      Introduced Variation Knockout of SLC38A3
                      Induced Change Tyrosine concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that knockout of SLC38A3 leads to the decrease of tyrosine levels compared with control group.
      Amino acid/polyamine transporter (AAPT)
            Integral membrane E16 (SLC7A5) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [5]
                      Introduced Variation Overexperisson of SLC7A5
                      Induced Change Tyrosine concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that co-overexperisson of SLC7A5 and SLC7A8 leads to the decrease of tyrosine levels compared with control group.
            L-type amino acid transporter 2 (LAT2) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [5]
                      Introduced Variation Overexperisson of SLC7A8
                      Induced Change Tyrosine concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that co-overexperisson of SLC7A5 and SLC7A8 leads to the decrease of tyrosine levels compared with control group.
      GPCR secretin (GPCR-2)
            Glucagon receptor (GCGR) Click to Show/Hide the Full List of Regulating Pair(s):   2 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair (1) Experim Info click to show the details of experiment for validating this pair [6]
                      Introduced Variation Antagonist (GRA1) of GCGR
                      Induced Change Tyrosine concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Hyperglycemic hyperosmolar syndrome [ICD-11: 5A20]
                      Details It is reported that antagonist of GCGR leads to the increase of tyrosine levels compared with control group.
               Regulating Pair (2) Experim Info click to show the details of experiment for validating this pair [7]
                      Introduced Variation Knockout of Gcgr
                      Induced Change Tyrosine concentration: increase (FC = 1.7)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Type 2 diabetes mellitus [ICD-11: 5A11]
                      Details It is reported that knockout of GCGR leads to the increase of tyrosine levels compared with control group.
      Hydrolases (EC 3)
            GTPase KRas (KRAS) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [8]
                      Introduced Variation Overexpression of KRAS
                      Induced Change Tyrosine concentration: decrease (FC = 0.92)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Lung cancer [ICD-11: 2C25]
                      Details It is reported that overexpression of KRAS leads to the decrease of tyrosine levels compared with control group.
            Leukotriene-C4 hydrolase (GGT1) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [9]
                      Introduced Variation Knockdown (siRNA) of GGT1
                      Induced Change Tyrosine concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Renal cell carcinoma [ICD-11: 2C90]
                      Details It is reported that knockdown of GGT1 leads to the increase of tyrosine levels compared with control group.
            Sulfatase sulf-1 (SULF1) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [10]
                      Introduced Variation Knockdown (shRNA) of SULF1
                      Induced Change Tyrosine concentration: decrease (FC = 0.47 / 0.48)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Ovarian cancer [ICD-11: 2C73]
                      Details It is reported that knockdown of SULF1 leads to the decrease of tyrosine levels compared with control group.
      Monocarboxylate porter (MNP)
            Monocarboxylate transporter 10 (SLC16A10) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [11]
                      Introduced Variation Overexpression of SLC16A10
                      Induced Change Tyrosine concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that overexpression of SLC16A10 leads to the increase of tyrosine levels compared with control group.
      Pore-forming PNC peptide (PNC)
            Cellular tumor antigen p53 (TP53) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [12]
                      Introduced Variation Knockout of TP53
                      Induced Change Tyrosine concentration: decrease (Log2 FC=0.8)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Colon cancer [ICD-11: 2B90]
                      Details It is reported that knockout of TP53 leads to the decrease of tyrosine levels compared with control group.
      Transcription factor (TF)
            Forkhead box protein O1 (FOXO1) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [13]
                      Introduced Variation Overexpression of Foxo1
                      Induced Change Tyrosine concentration: decrease (FC = 0.50)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that overexpression of Foxo1 leads to the decrease of tyrosine levels compared with control group.
            Myc proto-oncogene protein (MYC) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [14]
                      Introduced Variation Knockdown (siRNA) of MYC
                      Induced Change Tyrosine concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Colorectal cancer [ICD-11: 2B91]
                      Details It is reported that knockdown of MYC leads to the decrease of tyrosine levels compared with control group.
      Zinc finger protein (ZIN)
            Protein snail homolog 1 (SNAI1) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [15]
                      Introduced Variation Knockdown (shRNA) of SNAI1
                      Induced Change Tyrosine concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Breast cancer [ICD-11: 2C60]
                      Details It is reported that knockdown of Snai1 leads to the increase of tyrosine levels compared with control group.
References
1 L-DOPA is an endogenous ligand for OA1. PLoS Biol. 2008 Sep 30;6(9):e236.
2 mTORC1 Activator SLC38A9 Is Required to Efflux Essential Amino Acids from Lysosomes and Use Protein as a Nutrient. Cell. 2017 Oct 19;171(3):642-654.e12.
3 SNAT2 silencing prevents the osmotic induction of transport system A and hinders cell recovery from hypertonic stress. FEBS Lett. 2005 Jun 20;579(16):3376-80.
4 Loss of function mutation of the Slc38a3 glutamine transporter reveals its critical role for amino acid metabolism in the liver, brain, and kidney. Pflugers Arch. 2016 Feb;468(2):213-27.
5 Identification of a membrane protein, LAT-2, that Co-expresses with 4F2 heavy chain, an L-type amino acid transport activity with broad specificity for small and large zwitterionic amino acids. J Biol Chem. 1999 Jul 9;274(28):19738-44.
6 Anti-diabetic efficacy and impact on amino acid metabolism of GRA1, a novel small-molecule glucagon receptor antagonist. PLoS One. 2012;7(11):e49572.
7 Polyomic profiling reveals significant hepatic metabolic alterations in glucagon-receptor (GCGR) knockout mice: implications on anti-glucagon therapies for diabetes. BMC Genomics. 2011 Jun 1;12:281.
8 Capturing the metabolomic diversity of KRAS mutants in non-small-cell lung cancer cells. Oncotarget. 2014 Jul 15;5(13):4722-31.
9 Impairment of gamma-glutamyl transferase 1 activity in the metabolic pathogenesis of chromophobe renal cell carcinoma. Proc Natl Acad Sci U S A. 2018 Jul 3;115(27):E6274-E6282.
10 Erratum to: Loss of HSulf-1 promotes altered lipid metabolism in ovarian cancer. Cancer Metab. 2014 Nov 4;2:24.
11 The human T-type amino acid transporter-1: characterization, gene organization, and chromosomal location. Genomics. 2002 Jan;79(1):95-103.
12 Integrative omics analysis of p53-dependent regulation of metabolism. FEBS Lett. 2018 Feb;592(3):380-393.
13 Metabolomic analysis of C2C12 myoblasts induced by the transcription factor FOXO1. FEBS Lett. 2019 Jun;593(12):1303-1312.
14 Global metabolic reprogramming of colorectal cancer occurs at adenoma stage and is induced by MYC. Proc Natl Acad Sci U S A. 2017 Sep 12;114(37):E7697-E7706.
15 Snail reprograms glucose metabolism by repressing phosphofructokinase PFKP allowing cancer cell survival under metabolic stress. Nat Commun. 2017 Feb 8;8:14374.

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