Sarcosine Explained

Sarcosine, also known as N-methylglycine, or monomethylglycine, is a amino acid with the formula CH3N(H)CH2CO2H. It exists at neutral pH as the zwitterion CH3N+(H)2CH2CO2, which can be obtained as a white, water-soluble powder. Like some 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. Sarcosine is a close relative of glycine, with a secondary amine in place of the primary amine.

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.[1]

Sarcosine is sweet to the taste.

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-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 an intermediate in the metabolism of choline to glycine.[2] 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.[3]

Industrial synthesis

Sarcosine can be produced industrially via the Strecker amino acid synthesis.

Surfactants

A variety of surfactants are produced from sarcosine, for instance sodium lauroyl sarcosinate.[4]

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.[5] [6]

Prostate cancer

Sarcosine has also been debated as a biomarker for prostate cancer cells.[7] [8] More recent 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.[9]

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.[10]

See also

Notes and References

  1. Book: 10.1002/047084289X.rn02457. N -Methylglycine . Encyclopedia of Reagents for Organic Synthesis . 2022 . Ganesh . Madhu . Rao . Madhuri P. . 1–4 . 9780471936237 .
  2. 10.1016/j.molmet.2019.05.012. Formate Metabolism in Health and Disease . 2020 . Pietzke . Matthias . Meiser . Johannes . Vazquez . Alexei . Molecular Metabolism . 33 . 23–37 . 31402327 . 7056922 .
  3. Allen RH, Stabler SP, Lindenbaum J . 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 . November 1993 . 7694037 . 10.1016/0026-0495(93)90198-W .
  4. Book: 10.1002/14356007.a25_747.pub2. Surfactants. Ullmann's Encyclopedia of Industrial Chemistry. 2019. Holmberg. Krister. 1–56. 9783527306732. 242339510.
  5. Lane HY, Huang CL, Wu PL, Liu YC, Chang YC, Lin PY, Chen PW, Tsai G . Glycine transporter I inhibitor, N-methylglycine (sarcosine), added to clozapine for the treatment of schizophrenia . Biological Psychiatry . 60 . 6 . 645–9 . September 2006 . 16780811 . 10.1016/j.biopsych.2006.04.005 . 42741531 .
  6. Tsai G, Lane HY, Yang P, Chong MY, Lange N . Glycine transporter I inhibitor, N-methylglycine (sarcosine), added to antipsychotics for the treatment of schizophrenia . Biological Psychiatry . 55 . 5 . 452–6 . March 2004 . 15023571 . 10.1016/j.biopsych.2003.09.012 . 35723786 .
  7. Struys EA, Heijboer AC, van Moorselaar J, Jakobs C, Blankenstein MA . Serum sarcosine is not a marker for prostate cancer . Annals of Clinical Biochemistry . 47 . Pt 3 . 282 . May 2010 . 20233752 . 10.1258/acb.2010.009270 . free .
  8. Pavlou M, Diamandis EP . The search for new prostate cancer biomarkers continues . Clinical Chemistry . 55 . 7 . 1277–9 . July 2009 . 19478024 . 10.1373/clinchem.2009.126870 . free .
  9. Khan . Amjad P . Rajendiran . Thekkelnaycke M . Bushra . Ateeq . Asangani . Irfan A . Athanikar . Jyoti N . Yocum . Anastasia K . Mehra . Rohit . Siddiqui . Javed . Palapattu . Ganesh . Wei . John T . Michailidis . George . Sreekumar . Arun . Chinnaiyan . Arul M . May 2013 . The Role of Sarcosine Metabolism in Prostate Cancer Progression . Neoplasia . 15 . 5 . 491–IN13 . 10.1593/neo.13314 . 1476-5586 . 3638352 . 23633921.
  10. Book: Rocke . Alan J. . 1993 . The Theory of Chemical Structure and the Structure of Chemical Theory . http://publishing.cdlib.org/ucpressebooks/view?docId=ft5g500723&chunk.id=d0e7179&toc.depth=1&toc.id=d0e7179&brand=eschol . 239–64 . The Quiet Revolution: Hermann Kolbe and the Science of Organic Chemistry . Berkeley . University of California . 978-0-520-08110-9.