Sarcosine, also known as N-methylglycine, or monomethylglycine, is a non-proteinogenic amino acid with the formula CH<sub>3</sub>N(H)CH<sub>2</sub>CO<sub>2</sub>H. 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. It was first isolated and named by the German chemist Justus von Liebig in 1847.
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. It has a mildly sweet taste.
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. These properties have led to its investigation as an adjunctive treatment in schizophrenia and major depressive disorder. Sarcosine has also been identified as an oncometabolite in prostate cancer, where elevated levels correlate with disease progression and metastatic potential.
Chemistry
Sarcosine is an achiral, colourless crystalline solid. It exists at neutral pH as the zwitterion CH<sub>3</sub>N<sup>+</sup>(H)<sub>2</sub>CH<sub>2</sub>CO<sub>2</sub><sup>−</sup>, It has a melting point of 208–212 °C (with decomposition) and is highly soluble in water (1480 g/L at 20 °C). Like most other amino acids, sarcosine converts to a cation at low pH and an anion at high pH, with the respective formulas CH<sub>3</sub>N<sup>+</sup>(H)<sub>2</sub>CH<sub>2</sub>CO<sub>2</sub>H and CH<sub>3</sub>N(H)CH<sub>2</sub>CO<sub>2</sub><sup>−</sup>. The pK<sub>a</sub> values are approximately 2.21 (carboxyl group) and 10.2 (amino group).
Surfactants
A variety of surfactants are produced from sarcosine, for instance sodium lauroyl sarcosinate.
Biochemistry
thumb|class=skin-invert-image|left|300px|upright=1.15|Simplified scheme of sarcosine–glycine interconversion.
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.
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.
Distribution
In humans, sarcosine is found at relatively low concentrations in the extracellular compartment, mitochondria, and peroxisomes. By blocking GlyT1, sarcosine elevates the extracellular concentration of glycine in the vicinity of NMDA receptors, thereby augmenting NMDA receptor-mediated neurotransmission. Long-term sarcosine administration (21 days) ameliorated chronic unpredictable stress-induced depressive behaviour in rats 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.
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.
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.
Prostate cancer
Sarcosine has been debated as a biomarker for prostate cancer cells. 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.
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.
See also
- Glycine
- Dimethylglycine
- Trimethylglycine
- Oncometabolism