Sarcosine

Sarcosine
Names
IUPAC name
N-Methylglycine
Systematic IUPAC name
(Methylamino)acetic acid
Identifiers
3D model (JSmol)
1699442
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.003.217
EC Number
  • 203-538-6
2018
KEGG
MeSH Sarcosine
UNII
  • InChI=1S/C3H7NO2/c1-4-2-3(5)6/h4H,2H2,1H3,(H,5,6) Y
    Key: FSYKKLYZXJSNPZ-UHFFFAOYSA-N Y
  • CNCC(O)=O
Properties
C3H7NO2
Molar mass 89.094 g·mol−1
Appearance White solid
Odor Odourless
Density 1.093 g/mL
Melting point 208 to 212 °C (406 to 414 °F; 481 to 485 K) experimental
1480 g L−1 (at 20 °C)[1]
log P 0.599
Acidity (pKa) 2.36
Basicity (pKb) 11.64
UV-vis (λmax) 260 nm
Absorbance 0.05
Thermochemistry
128.9 J K−1 mol−1
−513.50–−512.98 kJ mol−1
−1667.84–−1667.54 kJ mol−1
Related compounds
Related alkanoic acids
Related compounds
 Dimethylacetamide
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
N verify (what is YN ?)
Infobox references

Sarcosine, also known as N-methylglycine, or monomethylglycine, is a non-proteinogenic amino acid with the formula CH3N(H)CH2CO2H. It is the N-methyl derivative of glycine, with a secondary amine in place of the primary amine, and occurs naturally in muscles and other body tissues as an intermediate in the metabolism of choline to glycine.[2] It was first isolated and named by the German chemist Justus von Liebig in 1847.[3]

Sarcosine is ubiquitous in biological materials. It is used in manufacturing biodegradable surfactants and toothpastes as well as in other applications. It is also a reagent in organic synthesis.[4] It has a mildly sweet taste.[5]

Pharmacologically, sarcosine functions as a competitive inhibitor of the glycine transporter type 1 (GlyT1), a co-agonist at the glycine binding site of the NMDA receptor, and, at higher concentrations, an agonist at the strychnine-sensitive glycine receptor.[6][7] These properties have led to its investigation as an adjunctive treatment in schizophrenia and major depressive disorder.[8] Sarcosine has also been identified as an oncometabolite in prostate cancer, where elevated levels correlate with disease progression and metastatic potential.[9]

Chemistry

Sarcosine is an achiral, colourless crystalline solid.[10] It exists at neutral pH as the zwitterion CH3N+(H)2CH2CO2−, It has a melting point of 208–212 °C (with decomposition) and is highly soluble in water (1480 g/L at 20 °C).[10] Like other amino acids, sarcosine exists as a zwitterion at physiological pH, with the amine group protonated and the carboxyl group deprotonated.[11] with the amine group protonated and the carboxyl group deprotonated, which can be obtained as a white, water-soluble powder. Like some other amino acids, sarcosine converts to a cation at low pH and an anion at high pH, with the respective formulas CH3N+(H)2CH2CO2H and CH3N(H)CH2CO2−. The pKa values are approximately 2.21 (carboxyl group) and 10.2 (amino group).[10]

Industrial synthesis

Sarcosine can be produced industrially from esters of chloroacetic acid.[12]

Surfactants

A variety of surfactants are produced from sarcosine, for instance sodium lauroyl sarcosinate.[13]

Biochemistry

Sarcosine is an intermediate and byproduct in glycine synthesis and degradation. Sarcosine is metabolized to glycine by the enzyme sarcosine dehydrogenase, while glycine-N-methyltransferase 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 an intermediate in the metabolism of choline to glycine.[14]

Sarcosine, like the related compounds dimethylglycine (DMG) and trimethylglycine (betaine, TMG), is formed via the metabolism of nutrients such as choline and methionine, which both contain methyl groups used in a wide range of biochemical reactions. Sarcosine 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.[15]

Distribution

In humans, sarcosine is found at relatively low concentrations in the extracellular compartment, mitochondria, and peroxisomes.[11] Tissues with measurable sarcosine concentrations include skeletal muscle and the prostate gland.[11] Its cellular levels are tightly regulated by the balance between GNMT-mediated synthesis and SARDH/PIPOX-mediated catabolism.

Pharmacology

Pharmacodynamics

Sarcosine acts as a competitive inhibitor of GlyT1, a glycine transporter that is predominantly expressed on glial cells and is responsible for the reuptake of glycine from the synaptic cleft in the central nervous system.[6][7][16] By blocking GlyT1, sarcosine elevates the extracellular concentration of glycine in the vicinity of NMDA receptors, thereby augmenting NMDA receptor-mediated neurotransmission.[16]

In addition to its indirect enhancement of NMDA receptor function via GlyT1 blockade, sarcosine directly acts as a co-agonist at the glycine binding site (also termed the GluN1 site) of the NMDA receptor.[7] It increases NMDA-mediated currents in a dose-dependent manner.[7] Sarcosine differs from glycine as a co-agonist in that it produces markedly less NMDA receptor desensitization at subsaturating concentrations.[7] At equivalent receptor occupancy (EC20 to EC50), sarcosine significantly slowed the rate of glycine-dependent desensitisation compared with glycine itself, whereas the rate of glycine-independent desensitisation was similar for both ligands.[7]

At concentrations higher than those required for GlyT1 inhibition or NMDA receptor co-agonism, sarcosine additionally activates strychnine-sensitive glycine receptors (GlyRs).[6] It evokes a chloride current that is dose-dependent, inhibited by strychnine, and shows a lack of additivity with glycine.[6] Sarcosine is less potent and efficacious than glycine at GlyRs, potentially due to steric constraints imposed by the N-methyl group within the glycine binding site on the receptor.[6] The GlyR agonism of sarcosine is relevant at concentrations frequently used in experimental settings (0.5–2 mM), complicating the pharmacological interpretation.[6]

Aside from effects on glycine-related structures and NMDA receptors, sarcosine has been shown to modulate AMPA receptor function and downstream mTOR signalling in rodent models of depression.[17] Long-term sarcosine administration (21 days) ameliorated chronic unpredictable stress-induced depressive behaviour in rats[18] In the rat forced swim test, a single systemic dose of sarcosine produced rapid antidepressant-like effects accompanied by increased phosphorylation of mTOR and its upstream kinases in the hippocampus, and these behavioural and molecular effects were abolished by pretreatment with the AMPA receptor antagonist NBQX or the mTOR inhibitor rapamycin.[17] Sarcosine also increased phosphorylation of the GluR1 subunit at the protein kinase A site Ser845, a change commonly interpreted as enhanced AMPA receptor membrane insertion.[17]

Cryo-EM study published in 2025 resolved the structure of human GlyT1 in complex with sarcosine at 2.8 Å resolution, revealing the transporter in an occluded conformation.[19]

Pharmacokinetics

Following oral administration, sarcosine is absorbed from the gastrointestinal tract. It is metabolised to glycine primarily by SARDH in the mitochondrial matrix and to a lesser extent by PIPOX in peroxisomes.[2][20]

Research

Schizophrenia

Early evidence suggests sarcosine is an effective and well-tolerated adjuvant to many antipsychotics except clozapine for the treatment of schizophrenia, showing significant reductions in both positive and negative symptoms.[21][22]

Prostate cancer

Sarcosine has been debated as a biomarker for prostate cancer cells.[23][24] Other research has suggested that sarcosine plays an active role in the progression of prostate cancer, as addition of sarcosine to prostate epithelial cells caused the emergence of a new invasive phenotype.[25]

History

Sarcosine was first isolated and named by the German chemist Justus von Liebig in 1847.

Jacob Volhard first synthesized it in 1862 while working in the lab of Hermann Kolbe. Prior to the synthesis of sarcosine, it had long been known to be a hydrolysis product of creatine, a compound found in meat extract. Under this assumption, by preparing the compound with methylamine and monochloroacetic acid, Volhard proved that sarcosine was N-methylglycine.[26]

See also

References

  1. ^ "Sarcosine CAS: 107-97-1". Retrieved 17 March 2026.
  2. ^ a b "Metabocard for Sarcosine (HMDB0000271)". Human Metabolome Database. Retrieved 11 March 2026.
  3. ^ Heger Z, et al. (2013). "Sarcosine as a Potential Prostate Cancer Biomarker—A Review". International Journal of Molecular Sciences. 14 (7): 13893–13908. doi:10.3390/ijms140713893. ISSN 1422-0067. PMC 3742224. PMID 23880848.
  4. ^ Ganesh M, Rao MP (2022). "N -Methylglycine". Encyclopedia of Reagents for Organic Synthesis. pp. 1–4. doi:10.1002/047084289X.rn02457. ISBN 9780471936237.
  5. ^ Pundir CS, Deswal R, Kumar P (July 2019). "Quantitative analysis of sarcosine with special emphasis on biosensors: a review". Biomarkers. 24 (5): 415–422. doi:10.1080/1354750X.2019.1615124. ISSN 1354-750X. PMID 31050554.
  6. ^ a b c d e f Zhang HX, Lyons-Warren A, Thio LL (2009). "The glycine transport inhibitor sarcosine is an inhibitory glycine receptor agonist". Neuropharmacology. 57 (5–6): 551–555. doi:10.1016/j.neuropharm.2009.07.019. ISSN 0028-3908. PMC 2836904. PMID 19619564.
  7. ^ a b c d e f Zhang HX, Hyrc K, Thio LL (2009). "The glycine transport inhibitor sarcosine is an NMDA receptor co-agonist that differs from glycine". The Journal of Physiology. 587 (13): 3207–3220. doi:10.1113/jphysiol.2009.168757. ISSN 0022-3751. PMC 2727032. PMID 19433577.
  8. ^ Lane H, et al. (2005). "Sarcosine or D-Serine Add-on Treatment for Acute Exacerbation of Schizophrenia: A Randomized, Double-blind, Placebo-Controlled Study". Archives of General Psychiatry. 62 (11): 1196–1204. doi:10.1001/archpsyc.62.11.1196. ISSN 0003-990X. PMID 16275807.
  9. ^ Sreekumar A, et al. (2009). "Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression". Nature. 457 (7231): 910–914. doi:10.1038/nature07762. ISSN 0028-0836. PMC 2724746. PMID 19212411.
  10. ^ a b c "Sarcosine (107-97-1)". ChemicalBook. Retrieved 11 March 2026.
  11. ^ a b c "Sarcosine – CID 1088". PubChem, National Center for Biotechnology Information. Retrieved 11 March 2026.
  12. ^ Koenig G, Lohmar E, Rupprich N (2000). "Chloroacetic Acids". Ullmann's Encyclopedia of Industrial Chemistry. doi:10.1002/14356007.a06_537. ISBN 3-527-30673-0.
  13. ^ Holmberg K (2019). "Surfactants". Ullmann's Encyclopedia of Industrial Chemistry. pp. 1–56. doi:10.1002/14356007.a25_747.pub2. ISBN 9783527306732. S2CID 242339510.
  14. ^ Pietzke M, Meiser J, Vazquez A (2020). "Formate Metabolism in Health and Disease". Molecular Metabolism. 33: 23–37. doi:10.1016/j.molmet.2019.05.012. ISSN 2212-8778. PMC 7056922. PMID 31402327.
  15. ^ Allen RH, Stabler SP, Lindenbaum J (November 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.
  16. ^ a b Chen JJ, Li Z, Pan H, Murphy DL, Tamir H, Koepsell H (2001). "The glycine transporter type 1 inhibitor N-[3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)propyl]sarcosine potentiates NMDA receptor-mediated responses in vivo and produces an antipsychotic profile in rodent behavior". The Journal of Neuroscience. 21 (16): 6348–6358. doi:10.1523/JNEUROSCI.21-16-06348.2001. ISSN 0270-6474. PMC 6763151. PMID 11487658.
  17. ^ a b c Chen KT, Tsai MH, Wu CH, Jou MJ, Wei IH, Huang CC (2015). "AMPA Receptor–mTOR Activation is Required for the Antidepressant-Like Effects of Sarcosine during the Forced Swim Test in Rats". Frontiers in Behavioral Neuroscience. 9: 162. doi:10.3389/fnbeh.2015.00162. ISSN 1662-5153. PMC 4471371. PMID 26150775.
  18. ^ Chen KT, Wu CH, Tsai MH, Wu YC, Jou MJ, Huang CC, et al. (2017). "Antidepressant-like effects of long-term sarcosine treatment in rats with or without chronic unpredictable stress". Behavioural Brain Research. 316: 1–10. doi:10.1016/j.bbr.2016.06.004. ISSN 0166-4328. PMID 27555541.
  19. ^ Li N, Wei Y, Li R, Meng Y, Zhao J, Bai Q, et al. (2025). "Modulation of the human GlyT1 by clinical drugs and cholesterol". Nature Communications. 16 (1): 2431. doi:10.1038/s41467-025-57613-z. ISSN 2041-1723. PMC 11897355. PMID 40069141.{{cite journal}}: CS1 maint: overridden setting (link)
  20. ^ "SARDH Gene – Sarcosine Dehydrogenase". GeneCards. Retrieved 11 March 2026.
  21. ^ Lane HY, Huang CL, Wu PL, Liu YC, Chang YC, Lin PY, et al. (September 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. S2CID 42741531.
  22. ^ Tsai G, Lane HY, Yang P, Chong MY, Lange N (March 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. S2CID 35723786.
  23. ^ 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.
  24. ^ Pavlou M, Diamandis EP (July 2009). "The search for new prostate cancer biomarkers continues". Clinical Chemistry. 55 (7): 1277–9. doi:10.1373/clinchem.2009.126870. PMID 19478024.
  25. ^ Rajendiran TM, Bushra A, Asangani IA, Athanikar JN, Yocum AK, Mehra R, et al. (May 2013). "The Role of Sarcosine Metabolism in Prostate Cancer Progression". Neoplasia. 15 (5): 491–IN13. doi:10.1593/neo.13314. ISSN 1476-5586. PMC 3638352. PMID 23633921.
  26. ^ Rocke AJ (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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