Sarcosine
Encyclopedia
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
, purine
s and serine
. The concentration of sarcosine in blood serum of normal human subjects is 1.59 ± 1.08 nanomolar.
, 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.
. Early evidence suggests that intake of 2 g/day sarcosine as add-on therapy to certain antipsychotics (not clozapine) 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. 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.
in 2009, sarcosine was reported to activate prostate cancer cells and to indicate the malignancy of prostate cancer cells when measured in urine. 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. Sarcosine levels seemed to control the invasiveness of the cancer.
However, this conclusion has been disputed. A German research team reported a different result in 2010. 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. A review of the literature reached a similar conclusion.
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 was long believed to be hydrosolate 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.
Glycine
Glycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...
synthesis and degradation. Sarcosine is metabolized to glycine by the enzyme sarcosine dehydrogenase
Sarcosine dehydrogenase
In enzymology, a sarcosine dehydrogenase is an enzyme that catalyzes the chemical reactionThe 3 substrates of this enzyme are sarcosine, acceptor, and H2O, whereas its 3 products are glycine, formaldehyde, and reduced acceptor....
, while glycine-N-methyl transferase
Glycine N-methyltransferase
In enzymology, a glycine N-methyltransferase is an enzyme that catalyzes the chemical reactionThus, the two substrates of this enzyme are S-adenosyl methionine and glycine, whereas its two products are S-adenosylhomocysteine and sarcosine....
generates sarcosine from glycine. Sarcosine is a natural amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
found in muscles and other body tissues. In the laboratory, it may be synthesized from chloroacetic acid
Chloroacetic acid
Chloroacetic acid, industrially known as monochloroacetic acid is the organochlorine compound with the formula ClCH2CO2H. This carboxylic acid is a useful building-block in organic synthesis.-Production:...
and methylamine
Methylamine
Methylamine is the organic compound with a formula of CH3NH2. This colourless gas is a derivative of ammonia, but with one H atom replaced by a methyl group. It is the simplest primary amine. It is sold as a solution in methanol, ethanol, THF, and water, or as the anhydrous gas in pressurized...
. Sarcosine is found naturally as an intermediate in the metabolism of choline
Choline
Choline is a water-soluble essential nutrient. It is usually grouped within the B-complex vitamins. Choline generally refers to the various quaternary ammonium salts containing the N,N,N-trimethylethanolammonium cation....
to glycine
Glycine
Glycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...
. 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
Methionine
Methionine is an α-amino acid with the chemical formula HO2CCHCH2CH2SCH3. This essential amino acid is classified as nonpolar. This amino-acid is coded by the codon AUG, also known as the initiation codon, since it indicates mRNA's coding region where translation into protein...
, 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
Glutathione
Glutathione is a tripeptide that contains an unusual peptide linkage between the amine group of cysteine and the carboxyl group of the glutamate side-chain...
, creatine
Creatine
Creatine is a nitrogenous organic acid that occurs naturally in vertebrates and helps to supply energy to all cells in the body, primarily muscle. This is achieved by increasing the formation of Adenosine triphosphate...
, purine
Purine
A purine is a heterocyclic aromatic organic compound, consisting of a pyrimidine ring fused to an imidazole ring. Purines, including substituted purines and their tautomers, are the most widely distributed kind of nitrogen-containing heterocycle in nature....
s and serine
Serine
Serine is an amino acid with the formula HO2CCHCH2OH. It is one of the proteinogenic amino acids. By virtue of the hydroxyl group, serine is classified as a polar amino acid.-Occurrence and biosynthesis:...
. The concentration of sarcosine in blood serum of normal human subjects is 1.59 ± 1.08 nanomolar.
Clinical significance
Sarcosine has no known toxicity, as evidenced by the lack of phenotypic manifestations of sarcosinemiaSarcosinemia
Sarcosinemia , also called hypersarcosinemia and SARDH deficiency, is a rare autosomal recessive metabolic disorder characterized by an increased concentration of sarcosine in blood plasma and urine...
, an inborn error of sarcosine metabolism. Sarcosinemia can result from severe folate deficiency
Folate deficiency
Folate deficiency is a lack of folic acid in the diet and the signs are often subtle. Folate deficiency anemia is the medical name given for the condition. -Symptoms:Loss of appetite, and weight loss can occur...
because of the folate requirement for the conversion of sarcosine to glycine.
Schizophrenia
Recently, sarcosine has been investigated in relation to the mental illness schizophreniaSchizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
. Early evidence suggests that intake of 2 g/day sarcosine as add-on therapy to certain antipsychotics (not clozapine) 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. 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
Glycine
Glycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...
concentrations in the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
thus causing increased NMDA receptor
NMDA receptor
The NMDA receptor , a glutamate receptor, is the predominant molecular device for controlling synaptic plasticity and memory function....
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.
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.Prostate cancer marker
In a paper published in the journal NatureNature (journal)
Nature, first published on 4 November 1869, is ranked the world's most cited interdisciplinary scientific journal by the Science Edition of the 2010 Journal Citation Reports...
in 2009, sarcosine was reported to activate prostate cancer cells and to indicate the malignancy of prostate cancer cells when measured in urine. 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. Sarcosine levels seemed to control the invasiveness of the cancer.
However, this conclusion has been disputed. A German research team reported a different result in 2010. 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. A review of the literature reached a similar conclusion.
History
Sarcosine was first isolated and named by the German chemist Justus von LiebigJustus von Liebig
Justus von Liebig was a German chemist who made major contributions to agricultural and biological chemistry, and worked on the organization of organic chemistry. As a professor, he devised the modern laboratory-oriented teaching method, and for such innovations, he is regarded as one of the...
in 1847, while Jacob Volhard
Jacob Volhard
Jacob Volhard was the German chemist who discovered, together with his student Hugo Erdmann, the Volhard-Erdmann cyclization reaction. He was also responsible for the improvement of the Hell-Volhard-Zelinsky halogenation....
first synthesized it in 1862.
Volhard successfully synthesized the compound while working the lab of Hermann Kolbe. Prior to the synthesis of sarcosine, it was long believed to be hydrosolate 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
Methylamine
Methylamine is the organic compound with a formula of CH3NH2. This colourless gas is a derivative of ammonia, but with one H atom replaced by a methyl group. It is the simplest primary amine. It is sold as a solution in methanol, ethanol, THF, and water, or as the anhydrous gas in pressurized...
and monochloroacetic acid.