General Information of MET (ID: META00135)
Name Betaine
Synonyms   Click to Show/Hide Synonyms of This Metabolite
Acidin pepsin; Acidin-pepsin; AcidinPepsin; Beaufour brand OF betaine citrate; Betaine; Betaine hydrochloride; Betaine orphan brand; Betaine, glycine; Boizot brand OF betaine aspartate; Cystadane; Fournier brand OF betaine ascorbate and hydrate; Glycine betaine; Hepastyl; Hydrochloride, betaine; Logeais brand OF betaine cyclobutyrate; Lycine; N,N,N-Trimethylglycine; Orphan brand OF betaine; Stea 16; Stea-16; Stea16; TRIMETHYL glycine; Trimethylaminoacetate; Trimethylammonioacetate; Trimethylammonioacetic acid; UPSA brand OF betaine citrate
Source Endogenous;Drug;Escherichia Coli Metabolite;Yeast Metabolite;Food;Drug;Cosmetic;Food additives;TCM Ingredients;Plant Metabolite; 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
248
HMDB ID
HMDB0000043
Formula
C5H12NO2
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
C00719
DrugBank ID
DB04455
ChEBI ID
41139
FooDB ID
FDB009020
ChemSpider ID
243
METLIN ID
287
Physicochemical Properties Molecular Weight 118.15 Topological Polar Surface Area 37.3
XlogP -0.1 Complexity 93.1
Heavy Atom Count 8 Rotatable Bond Count 2
Hydrogen Bond Donor Count 1 Hydrogen Bond Acceptor Count 2
Function
Betaine (CAS: 107-43-7), also known as N,N,N-trimethylglycine, was named after its discovery in sugar beet (Beta vulgaris) in the 19th century. It is a small N-trimethylated amino acid, existing in zwitterionic form at neutral pH. It is now often called glycine betaine to distinguish it from other betaines that are widely distributed in microorganisms, plants, and animals. Many naturally occurring betaines serve as organic osmolytes, substances synthesized or taken up from the environment by cells for protection against osmotic stress, drought, high salinity, or high temperature. Intracellular accumulation of betaines permits water retention in cells, thus protecting from the effects of dehydration. Betaine functions as a methyl donor in that it carries and donates methyl functional groups to facilitate necessary chemical processes. In particular, it methylates homocysteine to methionine, also producing N,N-dimethylglycine. The donation of methyl groups is important to proper liver function, cellular replication, and detoxification reactions. Betaine also plays a role in the manufacture of carnitine and serves to protect the kidneys from damage. Betaine comes from either the diet or by the oxidation of choline. Betaine insufficiency is associated with metabolic syndrome, lipid disorders, and diabetes, and may have a role in vascular and other diseases. Betaine is important in development, from the pre-implantation embryo to infancy. Betaine is also widely regarded as an anti-oxidant. Betaine has been shown to have an inhibitory effect on NO release in activated microglial cells and may be an effective therapeutic component to control neurological disorders. As a drug, betaine hydrochloride has been used as a source of hydrochloric acid in the treatment of hypochlorhydria. Betaine has also been used in the treatment of liver disorders, for hyperkalemia, for homocystinuria, and for gastrointestinal disturbances (Martindale, The Extra Pharmacopoeia, 30th Ed, p1341).
Regulatory Network
Full List of Protein(s) Regulating This Metabolite
      Apolipoprotein (Apo)
            Apolipoprotein A-II (APOA2) 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 Mutation (-265T >C(rs5082)) of APOA2
                      Induced Change Betaine concentration: increase (FC = 1.18)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Obesity [ICD-11: 5B81]
                      Details It is reported that mutation (-265T >C(rs5082)) of APOA2 leads to the increase of betaine levels compared with control group.
      GPCR secretin (GPCR-2)
            Glucagon receptor (GCGR) 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 Gcgr
                      Induced Change Betaine concentration: increase (FC = 2.8)
                      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 betaine levels compared with control group.
      High mobility group N (HMGN)
            Nucleosome-binding protein 45 (NBP-45) 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 Knockout of Hmgn5
                      Induced Change Betaine concentration: decrease (FC = 0.48)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that knockout of Hmgn5 leads to the decrease of betaine levels compared with control group.
      Hydrolases (EC 3)
            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 [4]
                      Introduced Variation Knockdown (siRNA) of GGT1
                      Induced Change Betaine 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 betaine levels compared with control group.
      Lyases (EC 4)
            Cystathionine gamma-lyase (CTH) 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 Knockout of Cth
                      Induced Change Betaine concentration: decrease (FC = 0.30)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Organic acid disorderss [ICD-11: 5C50]
                      Details It is reported that knockout of Cth leads to the decrease of betaine 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 [6]
                      Introduced Variation Knockout of TP53
                      Induced Change Betaine concentration: increase (Log2 FC=1.81)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Colon cancer [ICD-11: 2B90]
                      Details It is reported that knockout of TP53 leads to the increase of betaine 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 [7]
                      Introduced Variation Overexpression of AN2
                      Induced Change Betaine concentration: decrease (FC = 0.50)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that overexpression of AN2 leads to the decrease of betaine levels compared with control group.
      Transferases (EC 2)
            Carnitine O-palmitoyltransferase 1 (CPT1) 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 Knockout of Cpt1c
                      Induced Change Betaine concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that knockout of Cpt1c leads to the decrease of betaine levels compared with control group.
References
1 Epigenomics and metabolomics reveal the mechanism of the APOA2-saturated fat intake interaction affecting obesity. Am J Clin Nutr. 2018 Jul 1;108(1):188-200.
2 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.
3 Metabolomics reveals a role for the chromatin-binding protein HMGN5 in glutathione metabolism. PLoS One. 2014 Jan 2;9(1):e84583.
4 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.
5 Hydrogen Sulfide Is a Regulator of Hemoglobin Oxygen-Carrying Capacity via Controlling 2,3-BPG Production in Erythrocytes. Oxid Med Cell Longev. 2021 Feb 13;2021:8877691.
6 Integrative omics analysis of p53-dependent regulation of metabolism. FEBS Lett. 2018 Feb;592(3):380-393.
7 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.
8 Metabolomic profiling reveals a role for CPT1c in neuronal oxidative metabolism. BMC Biochem. 2012 Oct 25;13:23.

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