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Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2014-10-29 21:50:37 UTC
HMDB IDHMDB00043
Secondary Accession NumbersNone
Metabolite Identification
Common NameBetaine
DescriptionBetaine, (or 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 (Wikipedia). 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 the metabolic syndrome, lipid disorders and diabetes, and may have a role in vascular and other diseases (PMID: 20346934 ). 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 (PMID: 22801281 ). 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. (From Martindale, The Extra Pharmacopoeia, 30th Ed, p1341).
Structure
Thumb
Synonyms
  1. (Carboxymethyl)trimethylammonium hydroxide inner salt
  2. (Trimethylammonio)acetate
  3. 1-Carboxy-N,N,N-trimethyl-Methanaminium
  4. 1-Carboxy-N,N,N-trimethyl-Methanaminium hydroxide
  5. 1-Carboxy-N,N,N-trimethylmethanaminium inner salt
  6. a-Earleine
  7. Abromine
  8. alpha-Earleine
  9. Aminocoat
  10. Betafin
  11. Betafin BCR
  12. Betafin BP
  13. Betaine
  14. Cystadane
  15. Ektasolve EE
  16. FinnStim
  17. Glycine betaine
  18. Glycocoll betaine
  19. Glycylbetaine
  20. Greenstim
  21. Loramine AMB 13
  22. Loramine AMB-13
  23. Lycine
  24. N,N,N-Trimethylglycine
  25. Oxyneurine
  26. Rubrine C
  27. Trimethylaminoacetate
  28. Trimethylaminoacetic acid
  29. Trimethylbetaine Glycine
  30. Trimethylglycine
  31. Trimethylglycocoll
Chemical FormulaC5H11NO2
Average Molecular Weight117.1463
Monoisotopic Molecular Weight117.078978601
IUPAC Name2-(trimethylazaniumyl)acetate
Traditional Namebetaine
CAS Registry Number107-43-7
SMILES
C[N+](C)(C)CC([O-])=O
InChI Identifier
InChI=1S/C5H11NO2/c1-6(2,3)4-5(7)8/h4H2,1-3H3
InChI KeyKWIUHFFTVRNATP-UHFFFAOYSA-N
Chemical Taxonomy
KingdomOrganic Compounds
Super ClassAmino Acids, Peptides, and Analogues
ClassAmino Acids and Derivatives
Sub ClassAlpha Amino Acids and Derivatives
Other Descriptors
  • Aliphatic Acyclic Compounds
  • a methylated methyl acceptor(Cyc)
  • amino-acid betaine(ChEBI)
  • glycine derivative(ChEBI)
Substituents
  • Carboxylic Acid Salt
  • Quaternary Ammonium Salt
Direct ParentAlpha Amino Acids and Derivatives
Ontology
StatusDetected and Quantified
Origin
  • Endogenous
Biofunction
  • Component of Glycine, serine and threonine metabolism
  • Component of Methionine metabolism
  • Osmolyte
ApplicationNot Available
Cellular locations
  • Cytoplasm
  • Extracellular
  • Mitochondria
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point293 - 301 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility611.0 mg/mL at 19 °CNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility1.86ALOGPS
logP-2.7ALOGPS
logP-4.5ChemAxon
logS-2ALOGPS
pKa (Strongest Acidic)2.26ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area40.13 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity52.82 m3·mol-1ChemAxon
Polarizability12.11 Å3ChemAxon
Spectra
SpectraMS/MSLC-MS1D NMR2D NMR
Biological Properties
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Mitochondria
Biofluid Locations
  • Blood
  • Saliva
  • Urine
Tissue Location
  • Adipose Tissue
  • Adrenal Cortex
  • Adrenal Gland
  • Bladder
  • Fibroblasts
  • Gonads
  • Gut
  • Intestine
  • Kidney
  • Liver
  • Pancreas
  • Placenta
  • Platelet
  • Prostate
  • Skeletal Muscle
  • Skin
  • Spleen
  • Stratum Corneum
  • Testes
Pathways
NameSMPDB LinkKEGG Link
Betaine MetabolismSMP00123map00260
Glycine and Serine MetabolismSMP00004map00260
Methionine MetabolismSMP00033map00270
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified33.6 (23.9-42.1) uMAdult (>18 years old)BothNormal details
BloodDetected and Quantified82.0 (20.0-144.0) uMAdult (>18 years old)BothNormal details
BloodDetected and Quantified72 +/- 22.4 uMAdult (>18 years old)Not SpecifiedNormal details
SalivaDetected and Quantified8.51 +/- 19.4 uMAdult (>18 years old)Female
Normal
    • Sugimoto et al. (...
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected and Quantified12.78 +/- 6.66 uMAdult (>18 years old)BothNormal
    • Dame, ZT. et al. ...
details
SalivaDetected and Quantified3.17 +/- 2.68 uMAdult (>18 years old)Female
Normal
    • Sugimoto et al. (...
details
SalivaDetected and Quantified10.59 +/- 10.82 uMAdult (>18 years old)FemaleNormal details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)BothNormal details
UrineDetected but not QuantifiedNot ApplicableAdult (>18 years old)BothNormal details
UrineDetected and Quantified11.5 (2.7-24.7) umol/mmol creatinineAdult (>18 years old)Both
Normal
details
UrineDetected and Quantified4.14 umol/mmol creatinineAdult (>18 years old)MaleNormal
    • Shaykhutdinov RA,...
details
UrineDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
UrineDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
UrineDetected and Quantified6.1 +/- 3.2 umol/mmol creatinineAdult (>18 years old)MaleNormal details
UrineDetected and Quantified49.6 (6.4-92.7) umol/mmol creatinineAdult (>18 years old)BothNormal details
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified42.1 +/- 19.3 uMAdult (>18 years old)Not SpecifiedHeart Transplant details
BloodDetected and Quantified32.5 (23.9-42.5) uMAdult (>18 years old)BothChronic renal failure details
BloodDetected and Quantified25.6 (23.4-36.6) uMAdult (>18 years old)BothContinuous ambulatory peritoneal dialysis (CAPD) details
BloodDetected and Quantified31.9 (28.3-36.2) uMAdult (>18 years old)BothHemodialysis details
SalivaDetected and Quantified6.43 +/- 0.37 uMAdult (>18 years old)MaleAlzheimer's disease details
SalivaDetected and Quantified14.04 +/- 14.30 uMAdult (>18 years old)MaleFrontotemporal lobe dementia details
SalivaDetected and Quantified45.82 +/- 51.32 uMAdult (>18 years old)BothLewy body disease details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)BothOral cancer details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)FemaleBreast cancer details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Not SpecifiedPancreatic cancer details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Not SpecifiedPeriodontal diseases details
UrineDetected and Quantified6.0 (0.0-16.0) umol/mmol creatinineAdult (>18 years old)BothLung cancer details
UrineDetected and Quantified51.2 +/- 7.6 umol/mmol creatinineAdult (>18 years old)Both3-Hydroxy-3- methylglutaryl-CoA lyase (HL) deficency details
UrineDetected and Quantified76.2 +/- 8 umol/mmol creatinineAdult (>18 years old)Both3-Hydroxy-3- methylglutaryl-CoA lyase (HL) deficency details
UrineDetected and Quantified210.1 +/- 16.4 umol/mmol creatinineAdult (>18 years old)BothArgininosuccinic aciduria (ASL) details
UrineDetected and Quantified20.1 +/- 4.7 umol/mmol creatinineAdult (>18 years old)BothPropionic acidemia details
UrineDetected and Quantified122 +/- 13.6 umol/mmol creatinineAdult (>18 years old)BothPropionic acidemia details
UrineDetected and Quantified8.5 +/- 0.4 umol/mmol creatinineAdult (>18 years old)BothPhenylketonuria details
UrineDetected and Quantified14.3 +/- 2.7 umol/mmol creatinineAdult (>18 years old)BothPhenylketonuria details
UrineDetected and Quantified14.2 +/- 0.9 umol/mmol creatinineAdult (>18 years old)BothMaple syrup urine disease details
UrineDetected and Quantified58 +/- 2.2 umol/mmol creatinineAdult (>18 years old)BothAminoaciduria details
Associated Disorders and Diseases
Disease References
Chronic renal failure
  1. McGregor DO, Dellow WJ, Lever M, George PM, Robson RA, Chambers ST: Dimethylglycine accumulates in uremia and predicts elevated plasma homocysteine concentrations. Kidney Int. 2001 Jun;59(6):2267-72. Pubmed: 11380830
Continuous ambulatory peritoneal dialysis
  1. McGregor DO, Dellow WJ, Lever M, George PM, Robson RA, Chambers ST: Dimethylglycine accumulates in uremia and predicts elevated plasma homocysteine concentrations. Kidney Int. 2001 Jun;59(6):2267-72. Pubmed: 11380830
Hemodialysis
  1. McGregor DO, Dellow WJ, Lever M, George PM, Robson RA, Chambers ST: Dimethylglycine accumulates in uremia and predicts elevated plasma homocysteine concentrations. Kidney Int. 2001 Jun;59(6):2267-72. Pubmed: 11380830
Lung Cancer
  1. Wishart DS, Knox C, Guo AC, Eisner R, Young N, Gautam B, Hau DD, Psychogios N, Dong E, Bouatra S, Mandal R, Sinelnikov I, Xia J, Jia L, Cruz JA, Lim E, Sobsey CA, Shrivastava S, Huang P, Liu P, Fang L, Peng J, Fradette R, Cheng D, Tzur D, Clements M, Lewis A, De Souza A, Zuniga A, Dawe M, Xiong Y, Clive D, Greiner R, Nazyrova A, Shaykhutdinov R, Li L, Vogel HJ, Forsythe I: HMDB: a knowledgebase for the human metabolome. Nucleic Acids Res. 2008 Oct 25. Pubmed: 18953024
Associated OMIM IDs
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB009020
KNApSAcK IDC00007291
Chemspider ID242
KEGG Compound IDC00719
BioCyc IDBETAINE
BiGG ID35786
Wikipedia LinkBetaine
NuGOwiki LinkHMDB00043
Metagene LinkHMDB00043
METLIN ID287
PubChem Compound247
PDB IDNot Available
ChEBI ID17750
References
Synthesis ReferenceMu, Yun; Guo, Xiao-hui. Improved process for preparation of betaine. Huaxue Yu Shengwu Gongcheng (2005), 22(7), 48-49.
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009 Feb 12;457(7231):910-4. Pubmed: 19212411
  2. Surtees R, Bowron A, Leonard J: Cerebrospinal fluid and plasma total homocysteine and related metabolites in children with cystathionine beta-synthase deficiency: the effect of treatment. Pediatr Res. 1997 Nov;42(5):577-82. Pubmed: 9357926
  3. Holm PI, Ueland PM, Kvalheim G, Lien EA: Determination of choline, betaine, and dimethylglycine in plasma by a high-throughput method based on normal-phase chromatography-tandem mass spectrometry. Clin Chem. 2003 Feb;49(2):286-94. Pubmed: 12560353
  4. Knopman D, Patterson M: An open-label, 24-week pilot study of the methyl donor betaine in Alzheimer disease patients. Alzheimer Dis Assoc Disord. 2001 Jul-Sep;15(3):162-5. Pubmed: 11522934
  5. Schwahn BC, Chen Z, Laryea MD, Wendel U, Lussier-Cacan S, Genest J Jr, Mar MH, Zeisel SH, Castro C, Garrow T, Rozen R: Homocysteine-betaine interactions in a murine model of 5,10-methylenetetrahydrofolate reductase deficiency. FASEB J. 2003 Mar;17(3):512-4. Epub 2003 Jan 22. Pubmed: 12551843
  6. Abdelmalek MF, Angulo P, Jorgensen RA, Sylvestre PB, Lindor KD: Betaine, a promising new agent for patients with nonalcoholic steatohepatitis: results of a pilot study. Am J Gastroenterol. 2001 Sep;96(9):2711-7. Pubmed: 11569700
  7. Abu Al-Soud W, Radstrom P: Effects of amplification facilitators on diagnostic PCR in the presence of blood, feces, and meat. J Clin Microbiol. 2000 Dec;38(12):4463-70. Pubmed: 11101581
  8. Sakamoto A, Ono H, Mizoguchi N, Sakura N: Betaine and homocysteine concentrations in infant formulae and breast milk. Pediatr Int. 2001 Dec;43(6):637-40. Pubmed: 11737741
  9. Schwab U, Torronen A, Toppinen L, Alfthan G, Saarinen M, Aro A, Uusitupa M: Betaine supplementation decreases plasma homocysteine concentrations but does not affect body weight, body composition, or resting energy expenditure in human subjects. Am J Clin Nutr. 2002 Nov;76(5):961-7. Pubmed: 12399266
  10. Chambers ST, Kunin CM: Isolation of glycine betaine and proline betaine from human urine. Assessment of their role as osmoprotective agents for bacteria and the kidney. J Clin Invest. 1987 Mar;79(3):731-7. Pubmed: 3546377
  11. Laryea MD, Steinhagen F, Pawliczek S, Wendel U: Simple method for the routine determination of betaine and N,N-dimethylglycine in blood and urine. Clin Chem. 1998 Sep;44(9):1937-41. Pubmed: 9732980
  12. Chung YL, Rider LG, Bell JD, Summers RM, Zemel LS, Rennebohm RM, Passo MH, Hicks J, Miller FW, Scott DL: Muscle metabolites, detected in urine by proton spectroscopy, correlate with disease damage in juvenile idiopathic inflammatory myopathies. Arthritis Rheum. 2005 Aug 15;53(4):565-70. Pubmed: 16082628
  13. Go EK, Jung KJ, Kim JY, Yu BP, Chung HY: Betaine suppresses proinflammatory signaling during aging: the involvement of nuclear factor-kappaB via nuclear factor-inducing kinase/IkappaB kinase and mitogen-activated protein kinases. J Gerontol A Biol Sci Med Sci. 2005 Oct;60(10):1252-64. Pubmed: 16282556
  14. Lever M, Slow S: The clinical significance of betaine, an osmolyte with a key role in methyl group metabolism. Clin Biochem. 2010 Jun;43(9):732-44. doi: 10.1016/j.clinbiochem.2010.03.009. Epub 2010 Mar 25. Pubmed: 20346934
  15. Amiraslani B, Sabouni F, Abbasi S, Nazem H, Sabet M: Recognition of betaine as an inhibitor of lipopolysaccharide-induced nitric oxide production in activated microglial cells. Iran Biomed J. 2012;16(2):84-9. Pubmed: 22801281

Enzymes

General function:
Involved in oxidoreductase activity, acting on CH-OH group of donors
Specific function:
Not Available
Gene Name:
CHDH
Uniprot ID:
Q8NE62
Molecular weight:
65358.005
General function:
Involved in zinc ion binding
Specific function:
Involved in the regulation of homocysteine metabolism. Converts betaine and homocysteine to dimethylglycine and methionine, respectively. This reaction is also required for the irreversible oxidation of choline.
Gene Name:
BHMT
Uniprot ID:
Q93088
Molecular weight:
44998.205
General function:
Involved in gamma-aminobutyric acid:sodium symporter ac
Specific function:
Transports betaine and GABA. May have a role in regulation of GABAergic transmission in the brain through the reuptake of GABA into presynaptic terminals, as well as in osmotic regulation.
Gene Name:
SLC6A12
Uniprot ID:
P48065
Molecular weight:
69367.655
References
  1. Basham JC, Chabrerie A, Kempson SA: Hypertonic activation of the renal betaine/GABA transporter is microtubule dependent. Kidney Int. 2001 Jun;59(6):2182-91. Pubmed: 11380820
General function:
Involved in zinc ion binding
Specific function:
Involved in the regulation of homocysteine metabolism. Converts homocysteine to methionine using S-methylmethionine (SMM) as a methyl donor.
Gene Name:
BHMT2
Uniprot ID:
Q9H2M3
Molecular weight:
33166.69