Sarcosine
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| Names |
| IUPAC name
2-(Methylamino)acetic acid[1]
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| Identifiers |
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CAS Number
|
107-97-1 Y |
| 3DMet |
B01190 |
|
Beilstein Reference
|
1699442 |
| ChEBI |
CHEBI:15611 Y |
| ChEMBL |
ChEMBL304383 Y |
| ChemSpider |
1057 Y |
| EC Number |
203-538-6 |
|
Gmelin Reference
|
2018 |
| Jmol 3D model |
Interactive image
Interactive image |
| KEGG |
C00213 Y |
| MeSH |
Sarcosine |
| PubChem |
1088 |
| UNII |
Z711V88R5F Y |
InChI
-
InChI=1S/C3H7NO2/c1-4-2-3(5)6/h4H,2H2,1H3,(H,5,6) Y
Key: FSYKKLYZXJSNPZ-UHFFFAOYSA-N Y
|
SMILES
-
CNCc(:[o]):[oH]
-
CNCC(O)=O
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| Properties |
|
Chemical formula
|
C3H7NO2 |
| Molar mass |
89.09 g·mol−1 |
| Appearance |
White crystalline powder |
| Odor |
Odourless |
| Density |
1.093 g/mL |
| Melting point |
208 to 212 °C (406 to 414 °F; 481 to 485 K) |
| Boiling point |
195.1 °C (383.2 °F; 468.2 K) |
|
Solubility in water
|
89.09 g L−1 (at 20 °C) |
| log P |
0.599 |
| Acidity (pKa) |
2.36 |
| Basicity (pKb) |
11.64 |
| UV-vis (λmax) |
260 nm |
| Absorbance |
0.05 |
| Thermochemistry |
|
Specific
heat capacity (C)
|
128.9 J K−1 mol−1 |
|
Std enthalpy of
formation (ΔfHo298)
|
−513.50–−512.98 kJ mol−1 |
|
Std enthalpy of
combustion (ΔcHo298)
|
−1667.84–−1667.54 kJ mol−1 |
| Related compounds |
|
Related alkanoic acids
|
- Dimethylglycine
- Glycocyamine
- Creatine
- N-Methyl-D-aspartic acid
- beta-Methylamino-L-alanine
- Guanidinopropionic acid
|
|
Related compounds
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Dimethylacetamide |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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| N verify (what is YN ?) |
| Infobox references |
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Sarcosine, also known as N-methylglycine, is an intermediate and byproduct in glycine synthesis and degradation. Sarcosine is metabolized to glycine by the enzyme sarcosine dehydrogenase, while glycine-N-methyl transferase generates sarcosine from glycine. Sarcosine is an amino acid derivative that is naturally found in muscles and other body tissues. In the laboratory, it may be synthesized from chloroacetic acid and methylamine. Sarcosine is found naturally as an intermediate in the metabolism of choline to glycine. Sarcosine is sweet to the taste and dissolves in water. It is used in manufacturing biodegradable surfactants and toothpastes as well as in other applications.
Sarcosine is ubiquitous in biological materials and is present in such foods as egg yolks, turkey, ham, vegetables, legumes, etc.
Sarcosine is formed from dietary intake of choline and from the metabolism of methionine, and is rapidly degraded to glycine, which, in addition to its importance as a constituent of protein, plays a significant role in various physiological processes as a prime metabolic source of components of living cells such as glutathione, creatine, purines and serine. The concentration of sarcosine in blood serum of normal human subjects is 1.4 ± 0.6 micromolar.[2]
Contents
- 1 Clinical significance
- 1.1 Schizophrenia
- 1.2 Depression
- 1.3 Prostate cancer marker
- 2 History
- 3 See also
- 4 References
Clinical significance
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This section needs more medical references for verification or relies too heavily on primary sources. Please review the contents of the section and add the appropriate references if you can. Unsourced or poorly sourced material may be challenged and removed. (August 2015) |
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Sarcosine has no known toxicity, as evidenced by the lack of phenotypic manifestations of sarcosinemia, an inborn error of sarcosine metabolism. Sarcosinemia can result from severe folate deficiency because of the folate requirement for the conversion of sarcosine to glycine.
Schizophrenia
Recently, sarcosine has been investigated in relation to the mental illness schizophrenia. Early evidence suggests that intake of 2 g/day sarcosine as add-on therapy to certain antipsychotics (not clozapine[3]) in schizophrenia gives significant additional reductions in both positive and negative symptomatology as well as the neurocognitive and general psychopathological symptoms that are common to the illness. Sarcosine had been tolerated well.[4] It is also under investigation for the possible prevention of schizophrenic illness during the prodromal stage of the disease. It acts as a type 1 glycine transporter inhibitor and a glycine agonist. It increases glycine concentrations in the brain thus causing increased NMDA receptor activation and a reduction in symptoms. As such, it might be an interesting treatment option and a possible new direction in the treatment of the mental illness in the future. A 2011 meta-analysis found adjunctive sarcosine to have a medium effect size for negative and total symptoms.[5]
Depression
Major depressive disorder is a complex disease and most currently available antidepressants aiming at monoamine neurotransmission exhibit limited efficacy and cognitive effects. N-methyl-D-aspartate (NMDA), one subtype of glutamate receptors, plays an important role in learning and memory. N-methyl-D-aspartic acid (NMDA) enhancing agents, such as Sarcosine (N-methylglycine), have been used as adjunctive therapy of schizophrenia. Preliminary clinic trials indicated that intake of Sarcosine improved not only psychotic but also depressive symptoms in patients with schizophrenia. [6]
A clinical study showed Sarcosine to be significantly more effective in treating Major Depression (substantially improved scores on the Hamilton Depression Rating Scale, Clinical Global Impression, and Global Assessment of Function) than Citalopram over a 6-week period. Sarcosine-treated patients were much more likely and quicker to remit and less likely to drop out of the study. Sarcosine was well tolerated without significant side effects.[7]
Prostate cancer marker
In a paper published in the journal Nature in 2009, sarcosine was reported to activate prostate cancer cells and to indicate the malignancy of prostate cancer cells when measured in urine.[8] Sarcosine was identified as a differential metabolite that was greatly increased during prostate cancer progression to metastasis and could be detected in urine. [9] Sarcosine levels seemed to control the invasiveness of the cancer.[8]
However, this conclusion has been disputed. A German research team reported a different result in 2010.[10] After measuring sarcosine levels in urine samples from prostate cancer patients, they concluded that measuring sarcosine in urine fails as a marker in prostate cancer detection and identification of aggressive tumors. In addition, another report concluded that serum sarcosine is not a marker for prostate cancer.[11] A review of the literature reached a similar conclusion.[12]
History
Sarcosine was first isolated and named by the German chemist Justus von Liebig in 1847, while Jacob Volhard first synthesized it in 1862.
Volhard successfully synthesized the compound while working in the lab of Hermann Kolbe. Prior to the synthesis of sarcosine, it had long been known to be hydrolysis product of creatine, a compound found in meat extract. Under this assumption, Volhard proposed that sarcosine was N-methylglycine, and proved so by preparing the compound with methylamine and monochloroacetic acid.[13]
See also
- Glycine
- Dimethylglycine
- Trimethylglycine
References
- ^ Sarcosine from PubChem
- ^ Allen RH, Stabler SP, Lindenbaum J (Nov 1993). "Serum betaine, N,N-dimethylglycine and N-methylglycine levels in patients with cobalamin and folate deficiency and related inborn errors of metabolism". Metabolism. 42 (11): 1448–60. doi:10.1016/0026-0495(93)90198-W. PMID 7694037.
- ^ Lane HY, Huang CL, Wu PL, Liu YC, Chang YC, Lin PY, Chen PW, Tsai G (Sep 2006). "Glycine transporter I inhibitor, N-methylglycine (sarcosine), added to clozapine for the treatment of schizophrenia". Biological Psychiatry. 60 (6): 645–9. doi:10.1016/j.biopsych.2006.04.005. PMID 16780811.
- ^ Tsai G, Lane HY, Yang P, Chong MY, Lange N (Mar 2004). "Glycine transporter I inhibitor, N-methylglycine (sarcosine), added to antipsychotics for the treatment of schizophrenia". Biological Psychiatry. 55 (5): 452–6. doi:10.1016/j.biopsych.2003.09.012. PMID 15023571.
- ^ Singh SP, Singh V (Oct 2011). "Meta-analysis of the efficacy of adjunctive NMDA receptor modulators in chronic schizophrenia". CNS Drugs. 25 (10): 859–85. doi:10.2165/11586650-000000000-00000. PMID 21936588.
- ^ https://clinicaltrials.gov/ct2/show/NCT00977353
- ^ Huang CC, Wei IH, Huang CL, Chen KT, Tsai MH, Tsai P, Tun R, Huang KH, Chang YC, Lane HY, Tsai GE (Nov 2013). "Inhibition of glycine transporter-I as a novel mechanism for the treatment of depression". Biological Psychiatry. 74 (10): 734–41. doi:10.1016/j.biopsych.2013.02.020. PMID 23562005.
- ^ a b 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 (Feb 2009). "Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression". Nature. 457 (7231): 910–4. Bibcode:2009Natur.457..910S. doi:10.1038/nature07762. PMC 2724746. PMID 19212411.
- ^ A Urine Test for Prostate Cancer?, Jennifer Couzin, Science NOW, 11 February 2009
- ^ Jentzmik F, Stephan C, Miller K, Schrader M, Erbersdobler A, Kristiansen G, Lein M, Jung K (Jul 2010). "Sarcosine in urine after digital rectal examination fails as a marker in prostate cancer detection and identification of aggressive tumours". European Urology. 58 (1): 12–8; discussion 20–1. doi:10.1016/j.eururo.2010.01.035. PMID 20117878.
- ^ Struys EA, Heijboer AC, van Moorselaar J, Jakobs C, Blankenstein MA (May 2010). "Serum sarcosine is not a marker for prostate cancer". Annals of Clinical Biochemistry. 47 (Pt 3): 282. doi:10.1258/acb.2010.009270. PMID 20233752.
- ^ Pavlou M, Diamandis EP (Jul 2009). "The search for new prostate cancer biomarkers continues". Clinical Chemistry. 55 (7): 1277–9. doi:10.1373/clinchem.2009.126870. PMID 19478024.
- ^ Rocke, Alan J. (1993). "The Theory of Chemical Structure and the Structure of Chemical Theory". The Quiet Revolution: Hermann Kolbe and the Science of Organic Chemistry. Berkeley: University of California. pp. 239–64. ISBN 978-0-520-08110-9.
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Neurotransmitters
|
|
| Amino acid-derived |
- Major excitatory/inhibitory systems: Glutamate system: Agmatine
- Aspartic acid (aspartate)
- Cycloserine
- Glutamic acid (glutamate)
- Glutathione
- Glycine
- GSNO
- GSSG
- Kynurenic acid
- NAA
- NAAG
- Proline
- Serine; GABA system: GABA
- GABOB
- GHB; Glycine system: α-Alanine
- β-Alanine
- Glycine
- Hypotaurine
- Proline
- Sarcosine
- Serine
- Taurine; GHB system: GHB
- T-HCA (GHC)
- Biogenic amines: Monoamines: 6-OHM
- Dopamine
- Epinephrine (adrenaline)
- Melatonin
- NAS (normelatonin)
- Norepinephrine (noradrenaline)
- Serotonin (5-HT); Trace amines:
- 3-Iodothyronamine
- N-Methylphenethylamine
- N-Methyltryptamine
- m-Octopamine
- p-Octopamine
- Phenylethanolamine
- Phenethylamine
- Synephrine
- Tryptamine
- m-Tyramine
- p-Tyramine; Others: Histamine
- Neuropeptides: See here instead.
|
|
| Lipid-derived |
- Endocannabinoids: 2-AG
- 2-AGE (noladin ether)
- 2-ALPI
- 2-OG
- AA-5-HT
- Anandamide (AEA)
- DEA
- LPI
- NADA
- NAGly
- OEA
- Oleamide
- PEA
- RVD-Hpα
- SEA
- Virodhamine (O-AEA)
- Neurosteroids: See here instead.
|
|
| Nucleobase-derived |
- Nucleosides: Adenosine system: Adenosine
- ADP
- AMP
- ATP
|
|
| Vitamin-derived |
- Cholinergic system: Acetylcholine
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|
| Miscellaneous |
- Gasotransmitters: Carbon monoxide (CO)
- Hydrogen sulfide (H2S)
- Nitric oxide (NO); Candidates: Acetaldehyde
- Ammonia (NH3)
- Carbonyl sulfide (COS)
- Nitrous oxide (N2O)
- Sulfur dioxide (SO2)
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|
Glycinergics
|
|
Receptor
(ligands) |
|
GlyR
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- Agonists: β-Alanine
- β-ABA (BABA)
- β-AIBA
- Caesium
- D-Alanine
- D-Serine
- GABA
- Glycine
- Hypotaurine
- Ivermectin
- L-Alanine
- L-Proline
- L-Serine
- L-Threonine
- MDL-27531
- Milacemide
- Picolinic acid
- Propofol
- Quisqualamine
- Sarcosine
- Taurine
- PAMs: Alcohols (e.g., brometone, chlorobutanol (chloretone), ethanol, tert-butanol (2M2P), tribromoethanol, trichloroethanol, trifluoroethanol)
- Alkylbenzene sulfonate
- Anandamide
- Barbiturates (e.g., pentobarbital, sodium thiopental)
- Chlormethiazole
- D12-116
- Dihydropyridines (e.g., nicardipine)
- Etomidate
- Ginseng constituents (e.g., ginsenosides (e.g., ginsenoside-Rf))
- Glutamic acid (glutamate)
- Ivermectin
- Ketamine
- Neuroactive steroids (e.g., alfaxolone, pregnenolone (eltanolone), pregnenolone acetate, minaxolone, Org 20599)
- Nitrous oxide
- Penicillin G
- Propofol
- Tamoxifen
- Tetrahydrocannabinol
- Triclofos
- Tropeines (e.g., atropine, bemesetron, cocaine, LY-278584, tropisetron, zatosetron)
- Volatiles/gases (e.g., chloral hydrate, chloroform, desflurane, diethyl ether (ether), enflurane, halothane, isoflurane, methoxyflurane, sevoflurane, toluene, trichloroethane (methyl chloroform), trichloroethylene)
- Xenon
- Zinc
- Antagonists: 2-Aminostrychnine
- 2-Nitrostrychnine
- 4-Phenyl-4-formyl-N-methylpiperidine
- αEMBTL
- Bicuculline
- Brucine
- Cacotheline
- Caffeine
- Colchicine
- Colubrine
- Cyanotriphenylborate
- Dendrobine
- Diaboline
- Endocannabinoids (e.g., 2-AG, anandamide (AEA))
- Gaboxadol (THIP)
- Gelsemine
- iso-THAZ
- Isobutyric acid
- Isonipecotic acid
- Isostrychnine
- Laudanosine
- N-Methylbicuculline
- N-Methylstrychnine
- N,N-Dimethylmuscimol
- Nipecotic acid
- Pitrazepin
- Pseudostrychnine
- Quinolines (e.g., 4-hydroxyquinoline, 4-hydroxyquinoline-3-carboxylic acid, 5,7-CIQA, 7-CIQ, 7-TFQ, 7-TFQA)
- RU-5135
- Sinomenine
- Strychnine
- Thiocolchicoside
- Tutin
- NAMs: Amiloride
- Benzodiazepines (e.g., bromazepam, clonazepam, diazepam, flunitrazepam, flurazepam)
- Corymine
- Cyanotriphenylborate
- Daidzein
- Dihydropyridines (e.g., nicardipine, nifedipine, nitrendipine)
- Furosemide
- Genistein
- Ginkgo constituents (e.g., bilobalide, ginkgolides (e.g., ginkgolide A, ginkgolide B, ginkgolide C, ginkgolide J, ginkgolide M))
- Imipramine
- NBQX
- Neuroactive steroids (e.g., 3α-androsterone sulfate, 3β-androsterone sulfate, deoxycorticosterone, DHEA sulfate, pregnenolone sulfate, progesterone)
- Opioids (e.g., codeine, dextromethorphan, dextrorphan, levomethadone, levorphanol, morphine, oripavine, pethidine, thebaine)
- Picrotoxin (i.e., picrotin and picrotoxinin)
- PMBA
- Riluzole
- Tropeines (e.g., bemesetron, LY-278584, tropisetron, zatosetron)
- Verapamil
- Zinc
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Transporter
(blockers) |
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GlyT1
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- ACPPB
- ALX-1393
- ALX-5407 (NFPS)
- AMG-747
- ASP2535
- Bitopertin (RG1678/RO4917838)
- CP-802079
- Ethanol
- Glycyldodecylamide
- GSK1018921
- LY-2365109
- Org 24598
- Org 25935 (SCH-900435)
- PF-02545920
- PF-03463275
- PF-04958242
- Sarcosine
- SSR-103,800
- SSR-504,734
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GlyT2
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- Amoxapine
- Ethanol
- NAGly
- Org 25543
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| Others |
- Precursors: 3-PG
- GHB
- L-Serine
- L-Theonine
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See also: GABAergics • GHBergics • Glutamatergics
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