General Information of MET (ID: META00443)
Name Asymmetric dimethylarginine
Synonyms   Click to Show/Hide Synonyms of This Metabolite
2-Amino-5-(amino-dimethylamino-methylidene)amino-pentanoate; 2-Amino-5-(amino-dimethylamino-methylidene)amino-pentanoic acid; ADMA; Dimethyl-L-arginine; Guanidino-N,N-dimethylarginine; N(5)-((Dimethylamino)iminomethyl)-L-ornithine; N(Omega),N(omega)-dimethyl-L-arginine; N(g),N(g)-Dimethylarginine; N(g)-Dimethylarginine; N(g1),N(g1)-Dimethylarginine; N,N-Dimethylarginine; NG,NG-Dimethyl-L-arginine; NG,NG-Dimethylarginine; NG-Dimethylarginine', Nomega,nomega'-dimethyl-L-arginine, 'Asymmetric dimethylarginine; Nomega,nomega-dimethyl-L-arginine
Source Endogenous;Yeast Metabolite;Food;Drug;Toxins/Pollutant;Microbial
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
123831
HMDB ID
HMDB0001539
Formula
C8H18N4O2
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
C03626
DrugBank ID
DB01686
ChEBI ID
17929
FooDB ID
FDB000508
ChemSpider ID
110375
METLIN ID
6309
Physicochemical Properties Molecular Weight 202.25 Topological Polar Surface Area 105
XlogP -3.6 Complexity 215
Heavy Atom Count 14 Rotatable Bond Count 6
Hydrogen Bond Donor Count 3 Hydrogen Bond Acceptor Count 4
Function
Asymmetric dimethylarginine (ADMA) is a naturally occurring chemical found in blood plasma. It is a metabolic by-product of continual protein modification processes in the cytoplasm of all human cells. It is closely related to L-arginine, a conditionally-essential amino acid. ADMA interferes with L-arginine in the production of nitric oxide, a key chemical to endothelial and hence cardiovascular health. Asymmetric dimethylarginine is created in protein methylation, a common mechanism of post-translational protein modification. This reaction is catalyzed by an enzyme set called S-adenosylmethionine protein N-methyltransferases (protein methylases I and II). The methyl groups transferred to create ADMA are derived from the methyl group donor S-adenosylmethionine, an intermediate in the metabolism of homocysteine. (Homocysteine is an important blood chemical, because it is also a marker of cardiovascular disease). After synthesis, ADMA migrates into the extracellular space and thence into blood plasma. Asymmetric dimethylarginine is measured using high performance liquid chromatography. ADMA has been identified as a uremic toxin according to the European Uremic Toxin Working Group.
Regulatory Network
Full List of Protein(s) Regulating This Metabolite
      Amino acid/polyamine transporter (AAPT)
            Cationic amino acid transporter 2 (SLC7A2) 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 Overexpression of SLC7A2
                      Induced Change Asymmetric dimethylarginine concentration: increase (FC = 1.13 - 1.35)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that overexpression of SLC7A2 leads to the increase of asymmetric dimethylarginine levels compared with control group.
            Solute carrier family 7 member 1 (SLC7A1) 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 Overexpression of SLC7A1
                      Induced Change Asymmetric dimethylarginine concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that overexpression of SLC7A1 leads to the decrease of asymmetric dimethylarginine 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 SLC7A1
                      Induced Change Asymmetric dimethylarginine concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that overexpression of SLC7A1 leads to the increase of asymmetric dimethylarginine levels compared with control group.
      Hydrolases (EC 3)
            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 [3]
                      Introduced Variation Knockdown (shRNA) of SULF1
                      Induced Change Asymmetric dimethylarginine concentration: increase (FC = 1.59)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Ovarian cancer [ICD-11: 2C73]
                      Details It is reported that knockdown of SULF1 leads to the increase of asymmetric dimethylarginine levels compared with control group.
      Multidrug/oligosaccharidyl-lipid/polysaccharide (MOP)
            Solute carrier SLC47A1 (MATE1) 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 Overexpression of SLC47A1
                      Induced Change Asymmetric dimethylarginine concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that overexpression of SLC47A1 leads to the increase of asymmetric dimethylarginine levels compared with control group.
      Organic ion transporter (OIT)
            Organic cation transporter 2 (OCT2) 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 Overexpression of SLC22A2
                      Induced Change Asymmetric dimethylarginine concentration: increase (FC = 1.24 - 1.38)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that overexpression of SLC22A2 leads to the increase of asymmetric dimethylarginine 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 [4]
                      Introduced Variation Knockout of TP53
                      Induced Change Asymmetric dimethylarginine concentration: decrease (Log2 FC=0.81)
                      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 asymmetric dimethylarginine levels compared with control group.
      Transcription factor (TF)
            Octamer-binding transcription factor 2 (OTF-2) 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 Overexpression of POU2F2
                      Induced Change Asymmetric dimethylarginine concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that overexpression of POU2F2 leads to the increase of asymmetric dimethylarginine levels compared with control group.
References
1 Transport of asymmetric dimethylarginine (ADMA) by cationic amino acid transporter 2 (CAT2), organic cation transporter 2 (OCT2) and multidrug and toxin extrusion protein 1 (MATE1). Amino Acids. 2013 Oct;45(4):989-1002.
2 Interaction of the cardiovascular risk marker asymmetric dimethylarginine (ADMA) with the human cationic amino acid transporter 1 (CAT1). J Mol Cell Cardiol. 2012 Sep;53(3):392-400.
3 Erratum to: Loss of HSulf-1 promotes altered lipid metabolism in ovarian cancer. Cancer Metab. 2014 Nov 4;2:24.
4 Integrative omics analysis of p53-dependent regulation of metabolism. FEBS Lett. 2018 Feb;592(3):380-393.

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