Sarcosine

Sarcosine
Names
IUPAC name
2-(Methylamino)acetic acid[1]
Identifiers
3DMet B01190
1699442
107-97-1 Yes
ChEBI CHEBI:15611 Yes
ChEMBL ChEMBL304383 Yes
ChemSpider 1057 Yes
EC number 203-538-6
2018
Jmol-3D images Image
Image
KEGG C00213 Yes
MeSH Sarcosine
PubChem 1088
UNII Z711V88R5F Yes
Properties
Molecular formula
 C3H7NO2
Molar mass 89.09 g·mol−1
Appearance White crystalline powder
Odor Odourless
Density 1.093 g/mL
Melting point 208 °C (406 °F; 481 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
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
Related compounds
 Dimethylacetamide
Except where noted otherwise, data is given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
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Infobox references

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 a natural amino acid 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]

Clinical significance

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.

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.[6]

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.[7] Sarcosine was identified as a differential metabolite that was greatly increased during prostate cancer progression to metastasis and could be detected in urine. Sarcosine levels were also increased in invasive prostate cancer cell lines relative to benign prostate epithelial cells.[8] Sarcosine levels seemed to control the invasiveness of the cancer.[7]

However, this conclusion has been disputed. A German research team reported a different result in 2010.[9] 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.[10] A review of the literature reached a similar conclusion.[11]

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 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.[12]

See also

References

  1. ↑ PubChem Sarcosine
  2. ↑ 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.
  3. ↑ Lane HY, Huang CL, Wu PL, Liu YC, Chang YC, Lin PY et al. (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.
  4. ↑ 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.
  5. ↑ 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.
  6. ↑ Huang CC, Wei IH, Huang CL, Chen KT, Tsai MH, Tsai P et al. (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.
  7. ↑ 7.0 7.1 Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J et al. (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.
  8. ↑ A Urine Test for Prostate Cancer?, Jennifer Couzin, Science NOW, 11 February 2009
  9. ↑ Jentzmik F, Stephan C, Miller K, Schrader M, Erbersdobler A, Kristiansen G et al. (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.
  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 (Jul 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.