Sarcosine

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
Names
IUPAC name
2-(Methylamino)acetic acid[1]
Identifiers
3D model (JSmol)
3DMet
1699442
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.003.217
EC Number
  • 203-538-6
2018
KEGG
MeSH Sarcosine
UNII
Properties
C3H7NO2
Molar mass 89.094 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)
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
128.9 J K−1 mol−1
Std enthalpy of
formation (ΔfH⦵298)
 −513.50–−512.98 kJ mol−1
Std enthalpy of
combustion (ΔcH⦵298)
 −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).
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Infobox references

Sarcosine is ubiquitous in biological materials and is present in such foods as egg yolks, turkey, ham, vegetables, legumes, etc.

Sarcosine, like the related compounds dimethylglycine (DMG) and trimethylglycine (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.[2]

Clinical significance

Toxicity


Motor impairment and respiratory issues have been observed in rats at 10mg/kg.

This equates to 800mg for an 80kg person.[3]

Schizophrenia

Sarcosine has been investigated in relation to schizophrenia. Early evidence suggests that intake of 2 g/day sarcosine as add-on therapy to certain antipsychotics (not clozapine[4]) 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.[5] 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.[6]

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 receptors (NMDARs), one subtype of glutamate receptor, play an important role in learning and memory, and NMDAR 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[7], and so may also be a useful supplement for treating depressive type schizoaffective disorders where rapid-acting glutamatergic antidepressants, particularly NMDA antagonists such as esketamine, can promote worsening of psychotic features (although risk-benefit analysis is ongoing as to this point).

Possible marker for prostate cancer

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.[8] Sarcosine levels seemed to control the invasiveness of the cancer.[8]

This conclusion has been disputed.[9][10][11]

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 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.[12]

gollark: I'd assume most of us have at least a vague idea of what the CAs used are.
gollark: I have no idea what a significant amount of these are actually doing.
gollark: Only 12? Huh.
gollark: Exciting.
gollark: h inheed.

See also

References
  1. Sarcosine from PubChem
  2. 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.
  3. Perry, Kenneth W.; Falcone, Julie F.; Fell, Matthew J.; Ryder, John W.; Yu, Hong; Love, Patrick L.; Katner, Jason; Gordon, Kimberly D.; Wade, Mark R.; Man, Teresa; Nomikos, George G.; Phebus, Lee A.; Cauvin, Annick J.; Johnson, Kirk W.; Jones, Carrie K.; Hoffmann, Beth J.; Sandusky, George E.; Walter, Magnus W.; Porter, Warren J.; Yang, Lijuan; Merchant, Kalpana M.; Shannon, Harlan E.; Svensson, Kjell A. (October 2008). "Neurochemical and behavioral profiling of the selective GlyT1 inhibitors ALX5407 and LY2365109 indicate a preferential action in caudal vs. cortical brain areas". Neuropharmacology. 55 (5): 743–754. doi:10.1016/j.neuropharm.2008.06.016. PMID 18602930.
  4. Lane HY, Huang CL, Wu PL, Liu YC, Chang YC, Lin PY, Chen PW, Tsai G (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.
  5. 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.
  6. Singh SP, Singh V (October 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.
  7. Clinical trial number NCT00977353 for "N-methylglycine (Sarcosine) Treatment for Depression" at ClinicalTrials.gov
  8. 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 (February 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. Lay summary – Science News (11 February 2009).
  9. Jentzmik F, Stephan C, Miller K, Schrader M, Erbersdobler A, Kristiansen G, Lein M, Jung K (July 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.
  10. 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.
  11. 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.
  12. 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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