General Information of MET (ID: META00411)
Name 3,4-Dihydroxybenzeneacetic acid
Synonyms   Click to Show/Hide Synonyms of This Metabolite
(3,4-Dihydroxyphenyl)-acetic acid; (3,4-Dihydroxyphenyl)acetate; (3,4-Dihydroxyphenyl)acetic acid; 2-(3,4-DIHYDROXYPHENYL)acetIC ACID; 2-(3,4-DIHYDROXYPHENYL)acetate; 3,4 Dihydroxyphenylacetic acid; 3,4-DHPOP; 3,4-Dihydroxy-benzeneacetic acid; 3,4-Dihydroxy-phenylacetic acid; 3,4-Dihydroxybenzeneacetate; 3,4-Dihydroxyphenyl acetate; 3,4-Dihydroxyphenyl acetic acid; 3,4-Dihydroxyphenylacetate; 3,4-Dihydroxyphenylacetic acid; 3,4-Dihydroxyphenylacetic acid, monosodium salt; DHY; DOPAC; Dihydroxyphenylacetate; Dihydroxyphenylacetic acid; Dopacetate; Dopacetic acid; HAA; Homogentisic acid; Homoprotocatechuate; Homoprotocatechuic acid
Source Endogenous;Food;Drug;TCM Ingredients;quercetin;Microbial; Herbal Ingredients In-Vivo Metabolism
Structure Type   Benzenediols  (Click to Show/Hide the Complete Structure Type Hierarchy)
Benzenoids
Phenols
Benzenediols
PubChem CID
547
HMDB ID
HMDB0001336
Formula
C8H8O4
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
C01161
DrugBank ID
DB01702
ChEBI ID
41941
FooDB ID
FDB000316
ChemSpider ID
532
METLIN ID
6170
Physicochemical Properties Molecular Weight 168.15 Topological Polar Surface Area 77.8
XlogP 0.5 Complexity 168
Heavy Atom Count 12 Rotatable Bond Count 2
Hydrogen Bond Donor Count 3 Hydrogen Bond Acceptor Count 4
Function
3,4-Dihydroxyphenylacetic acid (DOPAC) is a phenolic acid. DOPAC is a neuronal metabolite of dopamine (DA). DA undergoes monoamine oxidase-catalyzed oxidative deamination to 3,4-dihydroxyphenylacetaldehyde (DOPAL), which is metabolized primarily into DOPAC via aldehyde dehydrogenase (ALDH2). The biotransformation of DOPAL is critical as previous studies have demonstrated this DA-derived aldehyde to be a reactive electrophile and toxic to dopaminergic cells. Known inhibitors of mitochondrial ALDH2, such as 4-hydroxy-2-nonenal (4HNE) inhibit ALDH2-mediated oxidation of the endogenous neurotoxin DOPAL. 4HNE is one of the resulting products of oxidative stress, thus linking oxidative stress to the uncontrolled production of an endogenous neurotoxin relevant to Parkinson's disease. In early-onset Parkinson disease, there is markedly reduced activities of both monoamine oxidase (MAO) A and B. The amount of DOPAC, which is produced during dopamine oxidation by MAO, is greatly reduced as a result of increased parkin overexpression. Administration of methamphetamine to animals causes loss of DA terminals in the brain and significant decreases in dopamine and dihydroxyphenylacetic acid (DOPAC) in the striatum. Renal dopamine produced in the residual tubular units may be enhanced during a sodium challenge, thus behaving appropriately as a compensatory natriuretic hormone; however, the renal dopaminergic system in patients afflicted with renal parenchymal disorders should address parameters other than free urinary dopamine, namely the urinary excretion of L-DOPA and metabolites. DOPAC is one of the major phenolic acids formed during human microbial fermentation of tea, citrus, and soy flavonoid supplements. DOPAC exhibits a considerable antiproliferative effect in LNCaP prostate cancer and HCT116 colon cancer cells. The antiproliferative activity of DOPAC may be due to its catechol structure. A similar association of the catechol moiety in the B-ring with antiproliferative activity was demonstrated for flavanones. DOPAC can be found in Gram-positive bacteria.
Regulatory Network
Full List of Protein(s) Regulating This Metabolite
      GPCR glutamate (GPCR-3)
            Glutamate receptor mGLU2 (mGluR2) 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 Knockout of Grm2
                      Induced Change 3,4-Dihydroxybenzeneacetic acid concentration: decrease (FC = 0.72)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that knockout of mGlu2/3 leads to the decrease of 3,4-dihydroxybenzeneacetic acid levels compared with control group.
            Glutamate receptor mGLU3 (mGluR3) 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 Knockout of Grm3
                      Induced Change 3,4-Dihydroxybenzeneacetic acid concentration: decrease (FC = 0.72)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that knockout of mGlu2/3 leads to the decrease of 3,4-dihydroxybenzeneacetic acid levels compared with control group.
      GPCR rhodopsin (GPCR-1)
            Dopamine D4 receptor (D4R) 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 [2]
                      Introduced Variation Knockout of Drd4
                      Induced Change 3,4-Dihydroxybenzeneacetic acid concentration: decrease (FC = 0.82)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that knockout of DRD4 leads to the decrease of 3,4-dihydroxybenzeneacetic acid levels compared with control group.
      Neuropeptide Y (NPY)
            Neuropeptide Y (NPY) 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 [3]
                      Introduced Variation Antagonist ([D-Trp32]NPY) of Npy
                      Induced Change 3,4-Dihydroxybenzeneacetic acid concentration: increase (FC = 1.60)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that Antagonist ([D-Trp32]NPY) of Npy leads to the increase of 3,4-dihydroxybenzeneacetic acid levels compared with control group.
               Regulating Pair (2) Experim Info click to show the details of experiment for validating this pair [3]
                      Introduced Variation Overexpression of Npy
                      Induced Change 3,4-Dihydroxybenzeneacetic acid concentration: increase (FC = 2.00)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that overexpression of Npy leads to the increase of 3,4-dihydroxybenzeneacetic acid levels compared with control group.
      Transcription factor (TF)
            R2R3-MYB (AN2) 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 [4]
                      Introduced Variation Overexpression of AN2
                      Induced Change 3,4-Dihydroxybenzeneacetic acid concentration: increase (FC = 2.04)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that overexpression of AN2 leads to the increase of 3,4-dihydroxybenzeneacetic acid levels compared with control group.
References
1 Decreased striatal dopamine in group II metabotropic glutamate receptor (mGlu2/mGlu3) double knockout mice. BMC Neurosci. 2013 Sep 22;14:102.
2 Dopamine D4 receptor knockout mice exhibit neurochemical changes consistent with decreased dopamine release. J Neurosci Methods. 2007 Nov 30;166(2):306-14.
3 Effects of neuropeptide Y (NPY) and [D-Trp32]NPY on monoamine and metabolite levels in dialysates from rat hypothalamus during feeding behavior. Neuropeptides. 1996 Aug;30(4):391-8.
4 Comprehensive Influences of Overexpression of a MYB Transcriptor Regulating Anthocyanin Biosynthesis on Transcriptome and Metabolome of Tobacco Leaves. Int J Mol Sci. 2019 Oct 16;20(20):5123.

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