Sarcosine

Sarcosine is a product of Glycine. It can be used as a cognitive enhancer and to treat schizophrenia.

This page features 76 unique references to scientific papers.

Summary

All Essential Benefits/Effects/Facts & Information

Sarcosine, also known as N-methylglycine, is a metabolite of glycine. It shares properties with both Glycine and D-Serine, though its effects are weaker.

Sarcosine supplementation can be used to alleviate symptoms of depression and schizophrenia, or improve cognition. It is absorbed more reliably by the body than D-serine, which can also treat similar conditions.

Sarcosine is being investigated for its connection to prostate cancer. It may be a biomarker for prostate cancer, which means that if sarcosine levels in the blood are higher than normal, it could be an indicator of prostate cancer. This doesn’t mean that sarcosine itself causes cancer. More research is needed to confirm this relationship.

Sarcosine’s main mechanism involves inhibiting a transporter, called GlyT1, which takes up glycine and D-serine into cells. This increases the levels of glycine and D-serine in the body and increases their effects.

It is unknown at this time if sarcosine supplementation is harmful. It may act as a co-carcinogen, meaning it doesn’t cause cancer, but increases the effects of other cancer-causing compounds.

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How to Take

Recommended dosage, active amounts, other details

The standard sarcosine dose is 30mg/kg of bodyweight, which correlates to an approximate dosage range of 2,045 – 2,727mg for people between 150 – 200 lbs.

Sarcosine is taken daily.

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Human Effect Matrix

The Human Effect Matrix looks at human studies (it excludes animal and in vitro studies) to tell you what effects sarcosine has on your body, and how strong these effects are.

Grade Level of Evidence
Robust research conducted with repeated double-blind clinical trials
Multiple studies where at least two are double-blind and placebo controlled
Single double-blind study or multiple cohort studies
Uncontrolled or observational studies only
Level of Evidence
? The amount of high quality evidence. The more evidence, the more we can trust the results.
Outcome Magnitude of effect
? The direction and size of the supplement's impact on each outcome. Some supplements can have an increasing effect, others have a decreasing effect, and others have no effect.
Consistency of research results
? Scientific research does not always agree. HIGH or VERY HIGH means that most of the scientific research agrees.
Notes
Symptoms of Schizophrenia Notable High See all 4 studies
While the magnitude of benefit seen with Sarcosine is comparable to both D-serine and glycine, it appears to require a much lower (more practical) dose than does glycine and is more reliable than D-serine
Cognition Low See 2 studies


1Sources and Structure

1.1. Structure

1.2. Biological Significance

Sarcosine is synthesized by the glycine N-methyltransferase (GMNT) enzyme which uses a methyl group from S-Adenosyl Methionine to donate to Glycine, creating sarcosine and S-adenosylhomocysteine.[1][2]

It can be metabolized by either the sarcosine dehydrogenase (SARDH) enzyme or pipecolic acid oxidase (PIPOX),[3][4] the former of which is highly expressed in the liver but not brain and converts sarcosine into glycine.[5]

Sarcosine is synthesized by one enzyme (which appears to modulate sarcosine concentrations in the body) and is degraded by one of two other enzymes

Due to being able to facilitate a conversion from SAMe into S-adenosylhomocysteine, sarcosine is involved in methyl donation and homeostasis[6] and the one-carbon cycle.[7] This pathway, and particularly the enzyme of synthesis (GMNT), appear to be fairly important as the enzyme constitutes more than 1% of all cytosolic proteins in the liver[8] and is upregulated in response to excess methionine.[9]

Sarcosine is involved in the one-carbon cycle alongside other methyl donating molecules, and the enzyme that creates sarcosine appears to be involved with regulating methionine concentrations in the body


2Pharmacology

2.1. Serum

Serum sarcosine concentrations independent of supplementation have been noted to be 102.3ng/mL and 80.8ng/mL in men and women respectively.[10]

2.2. Excretion

Mean urine concentrations of sarcosine have been noted to be 138.5ng/mL and 94.8ng/mL (men and women)[10] and urinary sarcosine has been correlated to both age and serum sarcosine in women (but not men) and is independent of BMI.[10] Urinary sarcosine is known to be correlated with urinary creatinine.[11]


3Neurology

3.1. Glutaminergic Neurotransmission

NMDA receptors (a subset of glutaminergic receptors) have a glycine binding site which has become a favorable target for enhancing glutaminergic function as it carries a lower risk for excitotoxicity than other pharmaceutical interventions.[12]

Sarcosine appears to be a co-agonist at the NMDA receptor (glycine binding site) similar to both glycine and D-serine although it has a potency of 26+/-3µM (ED50 value).[13] Previous research[14][15] failed to find such an effect, and relative to glycine (EC50 of 61+/-8nM) sarcosine appears much weaker as 300µM of sarcosine is less potent than 3µM of glycine in vitro.[13]

When matched at the EC50 value, sarcosine appears to induce less desensitization than does glycine (did not extend to EC20 nor saturation, desensitization was 48+/-6% with sarcosine and 85+/-3% with glycine) and produces a larger calcium influx than does glycine.[13] This calcium influx from NMDA receptors is vital to signalling through the neuron[16][17]

Sarcosine is an agonist at the glycine binding site of NMDA receptors, and while it may be more potent when matched for the EC50 values it is practically weaker since it requires a much larger EC50 value to induce signalling. If the value is matched, however, then sarcosine is better at enhancing glutaminergic signalling

3.2. Glycinergic Neurotransmission

Sarcosine appears to be a glycine transporter 1 inhibitor (GlyT1; present on glial cells and helps regulate glycine concentrations[18]), blocking the reuptake of Glycine.[19][20][21] This inhibition occurs somewhere in the range of 40-150µM, and although the increased amount of glycine can enhance glycinergic signalling inhibition does not appear to explain all the signalling from sarcosine.[22]

Sarcosine can act on glycinergic receptors with an EC50 value of 3.2+/-0.7mM (3,200µM), which is significantly less potent than glycine (60μM).[22] 100μM sarcosine failed to elicit any activation.[22]

Appears to prevent glycine reuptake into glial cells and thus increase the exposure of glycine to the synapse, which appears to be the main mechanism. Although sarcosine can directly act on glycine receptors, it is quite weak at doing so relative to glycine

3.3. Memory and Learning

Activity at the glycine binding site of the NMDA receptors appears to enhance cognition secondary to enhancing NMDA signalling which can affect both youth and older rats, which is evident with synthetic agonists,[23][24] mice lacking the Gly1T transporter (which sarcosine inhibits) and thus having higher Glycine levels in the synapse,[25][26] as well as both glycine and D-Serine supplementation. Sarcosine's inhibition of Gly1T is thought to underlie cognitive promoting effects secondary to increasing synaptic levels of glycine and D-serine, since although sarcosine can directly act as a coagonist[13] it is significantly less potent than the other two.

Secondary to increasing synaptic levels of D-serine and glycine, sarcosine is thought to possess cognitive promoting effects in otherwise healthy and young rodents and humans

Social memory performance has been noted to be enhanced with GlyT1 transportation inhibitors (a deriviative of sarcosine in this study) and D-Serine.[27] Sarcosine is also able to attenuate the impairments of social memory,[27] motor coordination,[28] and novel object recognition[29] induced by NMDA antagonists.

GlyT1 inhibitors seem to have similar cognitive enhancing properties as D-serine (as they increase synaptic D-serine concentrations), although it is fairly underresearched

3.4. Schizophrenia

NMDA signalling itself is thought to be perturbed in schizophrenic persons[30][31][32][33] (and antagonists such as PCP cause or exacerbate schizophrenic symptoms[34]) and since agonists of the glycine modulatory site such as D-Serine are reduced in schizophrenic persons[35] it is thought that the reduced NMDA function may be indirectly through reduced glycine binding site activity.

Glycine transport inhibitors (of which sarcosine is[20][21]) appear to be useful in the treatment of schizophrenia secondary to increasing glycine and D-serine concentrations in the synapse, which encourages glycinergic and NMDA signalling.[36][37] There are two main glycine transporters (GlyT1 and GlyT2) with 50% homology, with GlyT1 being the target of sarcosine and the more prominent one expressed on glial cells[38][39][40] and possibly colocalized with NMDA receptors[40][41] whereas GlyT2 is localized to neurons and less expressed overall[41] and tends to be localized with the glyinergic receptors.[42][38][43] Since GlyT1 is more apparently involved with NMDA signalling, it is thought to be more relevant to the treatment of schizophrenia.

Similar to the theory behind SSRIs (which block reuptake of serotonin), glycine transport inhibitors can block the uptake of glycine and leave more present in the synapse to signal. The subsequently enhanced NMDA signalling from the higher glycine levels appears to be therapeutic for schizophenia

When looking at studies using sarcosine, 2,000mg sarcosine daily for six weeks in addition to antipsychotics noted improvements in symptoms in the range of 14-16% (BPRS and PANSS rating scales)[44] reaching up to around 20% symptom reduction relative to control.[45][46]

One study in persons on clozapine failed to find a benefit with sarcosine therapy at 2,000mg[47] which is similar to null results seen with D-serine.[48] Since clozapine is thought to be antipsychotic via D-serine signalling[49] this signalling pathway may already be saturated in persons on clozapine.

This magnitude of response seen with sarcosine is somewhat comparable to D-Serine at a similar dose,[50] Glycine at a higher dose (800mg/kg),[51][52] and D-cycloserine.[53][54] In direct comparative studies, however, sarcosine has been twice noted to outperform D-serine[45][46] which may be due to the unreliability seen with D-serine supplementation.

It should be noted that some studies by the author Guochuan Tsai have potential conflicts of interest due to the aforementioned being the creator of sarcosine (US patent 6228875[55]) alongside Joseph Coyle. These studies include the following,[44][45][47][46] although publication bias does not seem likely as the authors have published negative results previously.[47]

Sarcosine at 2,000mg appears to be just as effective as D-serine for treating symptoms of schizophrenia when looking at the magnitude of benefit, but sarcosine seems to be more reliable and is thus currently seen as being a better therapeutic alternative

3.5. Depression

Inhibition of GlyT1 is thought to be a novel treatment for depression, and has been implicated in preliminary evidence as being more potent than the reference drug citalopram.[56] Antidepressant effects have previously been noted with D-Serine,[57] thought to be related to enhancing glutaminergic neurotransmission.

Although it is not currently well researched, sarcosine may have anti-depressant properties secondary to enhancing glutaminergic neurotransmission

3.6. Addiction

D-Serine has been well investigated for its usage in treating cocaine dependency, and this appears to extend to both other agonsits at the glycine binding site of NMDA receptors (cycloserine) and to sarcosine as well.[58]

May hold the same anti-addictive properties as D-serine in response to cocaine


4Interactions with Cancer Metabolism

4.1. Prostate

Sarcosine appears to be elevated in the urine of persons with prostate cancer and thus potentially useful as a biomarker[59][60] and also appears to be elevated in the tumor itself[61] which is likely related to an increase in the enzyme that synthesizes sarcosine (GMNT) with reductions in degratory enzymes.[60] Its usage as a biomarker of prostate cancer rivals that of prostate specific antigen (PSA)[62][63][64] and is useful in persons with low PSA[65] although it does not show a relation to stage of cancer.[11][66]

Sarcosine is elevated in persons with prostate cancer, and the elevation is thought to be reflective of prostate cancer (as a biomarker). While it may be able to detect the presence of prostate tumors, it does not appear to be reliable in predicting the stage of prostate cancer

The oncogenic protein HER2/neu (overexpression of which is associated with tumor development in various cancers[67][68] including prostate,[69] and may promote disease progression via NF-kB[70]) appears to have its protein content upregulated after exposure to sarcosine of 25-100μM although there were no changes in the phosphorylation thereof.[71]In vitro studies have noted that application of high levels of sarcosine (1,500µM) can increase intracellular concentrations in this concentration (106µM) although lower extracellular levels of sarcosine (10µM) are not large enough (270nM).[72]

In benign prostate cells, increasing sarcosine concentrations seems to induce an invasive phenotype[59] thought to be indepedent of the androgen receptor (not affected elsewhere[71]). In PC-3 prostatic cancer cells, sarcosine (10-1,500µM) showed time-dependent changes in antioxidant status of these cells (reduction at 24 hours yet an increase at 48 hours) with the higher concentrations;[72] the implications of these changes for cancer progression are not clear.

It is unclear what mediates these pro-oncogenic effects as sarcosine does not appear to be inhernetly mutagenic,[73] although sarcosine has been noted to interact with the TMEFF2 protein[74] and it is also involved in the one-carbon cycle (of which an insufficiency of activity, resulting in hypomethylation, is known to be pro-oncogenic and causes cell division[75][76]).

Sarcosine may have pro-oncogenic effects without apparent mutagenic effects (furthers cancer growth when present without inherently causing cancer), yet this information is currently based of cell cultures. There are currently no animal models to support this hypothesis although it seems plausible

Scientific Support & Reference Citations

References

  1. Yeo EJ, Wagner C Tissue distribution of glycine N-methyltransferase, a major folate-binding protein of liver . Proc Natl Acad Sci U S A. (1994)
  2. Kerr SJ Competing methyltransferase systems . J Biol Chem. (1972)
  3. Porter DH, Cook RJ, Wagner C Enzymatic properties of dimethylglycine dehydrogenase and sarcosine dehydrogenase from rat liver . Arch Biochem Biophys. (1985)
  4. Dodt G, et al L-Pipecolic acid oxidase, a human enzyme essential for the degradation of L-pipecolic acid, is most similar to the monomeric sarcosine oxidases . Biochem J. (2000)
  5. Bergeron F, et al Molecular cloning and tissue distribution of rat sarcosine dehydrogenase . Eur J Biochem. (1998)
  6. Wang YC, et al Glycine-N methyltransferase expression in HepG2 cells is involved in methyl group homeostasis by regulating transmethylation kinetics and DNA methylation . J Nutr. (2011)
  7. Cook RJ, Wagner C Glycine N-methyltransferase is a folate binding protein of rat liver cytosol . Proc Natl Acad Sci U S A. (1984)
  8. Heady JE, Kerr SJ Purification and characterization of glycine N-methyltransferase . J Biol Chem. (1973)
  9. Rowling MJ, et al Hepatic glycine N-methyltransferase is up-regulated by excess dietary methionine in rats . J Nutr. (2002)
  10. Meyer TE, et al A reproducible and high-throughput HPLC/MS method to separate sarcosine from α- and β-alanine and to quantify sarcosine in human serum and urine . Anal Chem. (2011)
  11. Jentzmik F, et al Sarcosine in urine after digital rectal examination fails as a marker in prostate cancer detection and identification of aggressive tumours . Eur Urol. (2010)
  12. Gray JA, Roth BL The pipeline and future of drug development in schizophrenia . Mol Psychiatry. (2007)
  13. Zhang HX, Hyrc K, Thio LL The glycine transport inhibitor sarcosine is an NMDA receptor co-agonist that differs from glycine . J Physiol. (2009)
  14. McBain CJ, et al Structural requirements for activation of the glycine coagonist site of N-methyl-D-aspartate receptors expressed in Xenopus oocytes . Mol Pharmacol. (1989)
  15. Rabe CS, Tabakoff B Glycine site-directed agonists reverse the actions of ethanol at the N-methyl-D-aspartate receptor . Mol Pharmacol. (1990)
  16. Zorumski CF, et al Calcium influx through N-methyl-D-aspartate channels activates a potassium current in postnatal rat hippocampal neurons . Neurosci Lett. (1989)
  17. Isaacson JS, Murphy GJ Glutamate-mediated extrasynaptic inhibition: direct coupling of NMDA receptors to Ca(2+)-activated K+ channels . Neuron. (2001)
  18. Eulenburg V, et al Glycine transporters: essential regulators of neurotransmission . Trends Biochem Sci. (2005)
  19. López-Corcuera B, et al Differential properties of two stably expressed brain-specific glycine transporters . J Neurochem. (1998)
  20. Herdon HJ, et al Pharmacological assessment of the role of the glycine transporter GlyT-1 in mediating high-affinity glycine uptake by rat cerebral cortex and cerebellum synaptosomes . Neuropharmacology. (2001)
  21. Mallorga PJ, et al Pharmacology and expression analysis of glycine transporter GlyT1 with {3H}-(N-{3-(4'-fluorophenyl)-3-(4'phenylphenoxy)propyl})sarcosine . Neuropharmacology. (2003)
  22. Zhang HX, Lyons-Warren A, Thio LL The glycine transport inhibitor sarcosine is an inhibitory glycine receptor agonist . Neuropharmacology. (2009)
  23. Moskal JR, et al GLYX-13: a monoclonal antibody-derived peptide that acts as an N-methyl-D-aspartate receptor modulator . Neuropharmacology. (2005)
  24. Burgdorf J, et al The N-methyl-D-aspartate receptor modulator GLYX-13 enhances learning and memory, in young adult and learning impaired aging rats . Neurobiol Aging. (2011)
  25. Tsai G, et al Gene knockout of glycine transporter 1: characterization of the behavioral phenotype . Proc Natl Acad Sci U S A. (2004)
  26. Yee BK, et al Disruption of glycine transporter 1 restricted to forebrain neurons is associated with a procognitive and antipsychotic phenotypic profile . J Neurosci. (2006)
  27. Shimazaki T, Kaku A, Chaki S D-Serine and a glycine transporter-1 inhibitor enhance social memory in rats . Psychopharmacology (Berl). (2010)
  28. Chan MH, et al Sarcosine attenuates toluene-induced motor incoordination, memory impairment, and hypothermia but not brain stimulation reward enhancement in mice . Toxicol Appl Pharmacol. (2012)
  29. Karasawa J, Hashimoto K, Chaki S D-Serine and a glycine transporter inhibitor improve MK-801-induced cognitive deficits in a novel object recognition test in rats . Behav Brain Res. (2008)
  30. Olney JW, Farber NB Glutamate receptor dysfunction and schizophrenia . Arch Gen Psychiatry. (1995)
  31. Lindsley CW, et al Progress towards validating the NMDA receptor hypofunction hypothesis of schizophrenia . Curr Top Med Chem. (2006)
  32. Coyle JT The glutamatergic dysfunction hypothesis for schizophrenia . Harv Rev Psychiatry. (1996)
  33. Coyle JT, Tsai G The NMDA receptor glycine modulatory site: a therapeutic target for improving cognition and reducing negative symptoms in schizophrenia . Psychopharmacology (Berl). (2004)
  34. Allen RM, Young SJ Phencyclidine-induced psychosis . Am J Psychiatry. (1978)
  35. Hashimoto K, et al Decreased serum levels of D-serine in patients with schizophrenia: evidence in support of the N-methyl-D-aspartate receptor hypofunction hypothesis of schizophrenia . Arch Gen Psychiatry. (2003)
  36. Hashimoto K Glycine transport inhibitors for the treatment of schizophrenia . Open Med Chem J. (2010)
  37. Bergeron R, et al Modulation of N-methyl-D-aspartate receptor function by glycine transport . Proc Natl Acad Sci U S A. (1998)
  38. Aragón C, López-Corcuera B Glycine transporters: crucial roles of pharmacological interest revealed by gene deletion . Trends Pharmacol Sci. (2005)
  39. Borowsky B, Mezey E, Hoffman BJ Two glycine transporter variants with distinct localization in the CNS and peripheral tissues are encoded by a common gene . Neuron. (1993)
  40. Smith KE, et al Cloning and expression of a glycine transporter reveal colocalization with NMDA receptors . Neuron. (1992)
  41. Zafra F, et al Regional distribution and developmental variation of the glycine transporters GLYT1 and GLYT2 in the rat CNS . Eur J Neurosci. (1995)
  42. Danysz W, Parsons CG Glycine and N-methyl-D-aspartate receptors: physiological significance and possible therapeutic applications . Pharmacol Rev. (1998)
  43. Zafra F, Aragón C, Giménez C Molecular biology of glycinergic neurotransmission . Mol Neurobiol. (1997)
  44. Tsai G, et al Glycine transporter I inhibitor, N-methylglycine (sarcosine), added to antipsychotics for the treatment of schizophrenia . Biol Psychiatry. (2004)
  45. Lane HY, et al Sarcosine or D-serine add-on treatment for acute exacerbation of schizophrenia: a randomized, double-blind, placebo-controlled study . Arch Gen Psychiatry. (2005)
  46. Lane HY, et al A randomized, double-blind, placebo-controlled comparison study of sarcosine (N-methylglycine) and D-serine add-on treatment for schizophrenia . Int J Neuropsychopharmacol. (2010)
  47. Lane HY, et al Glycine transporter I inhibitor, N-methylglycine (sarcosine), added to clozapine for the treatment of schizophrenia . Biol Psychiatry. (2006)
  48. Tsai GE, et al D-serine added to clozapine for the treatment of schizophrenia . Am J Psychiatry. (1999)
  49. Tanahashi S, et al Clozapine, but not haloperidol, enhances glial D-serine and L-glutamate release in rat frontal cortex and primary cultured astrocytes . Br J Pharmacol. (2012)
  50. Tsai G, et al D-serine added to antipsychotics for the treatment of schizophrenia . Biol Psychiatry. (1998)
  51. Heresco-Levy U, et al Efficacy of high-dose glycine in the treatment of enduring negative symptoms of schizophrenia . Arch Gen Psychiatry. (1999)
  52. Heresco-Levy U, Silipo G, Javitt DC Glycinergic augmentation of NMDA receptor-mediated neurotransmission in the treatment of schizophrenia . Psychopharmacol Bull. (1996)
  53. van Berckel BN, et al Efficacy and tolerance of D-cycloserine in drug-free schizophrenic patients . Biol Psychiatry. (1996)
  54. Heresco-Levy U, et al Placebo-controlled trial of D-cycloserine added to conventional neuroleptics, olanzapine, or risperidone in schizophrenia . Am J Psychiatry. (2002)
  55. Methods for treating neuropsychiatric disorders
  56. Huang CC, et al Inhibition of Glycine Transporter-I as a Novel Mechanism for the Treatment of Depression . Biol Psychiatry. (2013)
  57. Otte DM, et al Effects of Chronic D-Serine Elevation on Animal Models of Depression and Anxiety-Related Behavior . PLoS One. (2013)
  58. Yang FY, et al D-cycloserine, sarcosine and D-serine diminish the expression of cocaine-induced conditioned place preference . J Psychopharmacol. (2013)
  59. Sreekumar A, et al Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression . Nature. (2009)
  60. Khan AP, et al The role of sarcosine metabolism in prostate cancer progression . Neoplasia. (2013)
  61. Jentzmik F, et al Sarcosine in prostate cancer tissue is not a differential metabolite for prostate cancer aggressiveness and biochemical progression . J Urol. (2011)
  62. Cao DL, et al Efforts to resolve the contradictions in early diagnosis of prostate cancer: a comparison of different algorithms of sarcosine in urine . Prostate Cancer Prostatic Dis. (2011)
  63. Cao DL, et al A multiplex model of combining gene-based, protein-based, and metabolite-based with positive and negative markers in urine for the early diagnosis of prostate cancer . Prostate. (2011)
  64. Bianchi F, et al Fully automated solid-phase microextraction-fast gas chromatography-mass spectrometry method using a new ionic liquid column for high-throughput analysis of sarcosine and N-ethylglycine in human urine and urinary sediments . Anal Chim Acta. (2011)
  65. Lucarelli G, et al Serum sarcosine increases the accuracy of prostate cancer detection in patients with total serum PSA less than 4.0 ng/ml . Prostate. (2012)
  66. Bohm L, et al Plasma sarcosine does not distinguish early and advanced stages of prostate cancer . S Afr Med J. (2012)
  67. Slamon DJ, et al Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene . Science. (1987)
  68. Slamon DJ, et al Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer . Science. (1989)
  69. Shi Y, et al Her-2/neu expression in prostate cancer: high level of expression associated with exposure to hormone therapy and androgen independent disease . J Urol. (2001)
  70. Koumakpayi IH, et al Hierarchical clustering of immunohistochemical analysis of the activated ErbB/PI3K/Akt/NF-kappaB signalling pathway and prognostic significance in prostate cancer . Br J Cancer. (2010)
  71. Dahl M, et al Sarcosine induces increase in HER2/neu expression in androgen-dependent prostate cancer cells . Mol Biol Rep. (2011)
  72. Cernei N, et al Effect of sarcosine on antioxidant parameters and metallothionein content in the PC-3 prostate cancer cell line . Oncol Rep. (2013)
  73. Hoorn AJ Dimethylglycine and chemically related amines tested for mutagenicity under potential nitrosation conditions . Mutat Res. (1989)
  74. Chen X, et al The tumor suppressor activity of the transmembrane protein with epidermal growth factor and two follistatin motifs 2 (TMEFF2) correlates with its ability to modulate sarcosine levels . J Biol Chem. (2011)
  75. Liu SP, et al Glycine N-methyltransferase-/- mice develop chronic hepatitis and glycogen storage disease in the liver . Hepatology. (2007)
  76. Dizik M, Christman JK, Wainfan E Alterations in expression and methylation of specific genes in livers of rats fed a cancer promoting methyl-deficient diet . Carcinogenesis. (1991)