Glycine is derived from threonine and from your diet.

Serine ↔ Glycine

Sarcosine ↔ Glycine

- Glycine helps to produce glutathione and sarcosine and is a conjugator of toxins (benzoic acid).

- Glycine was found highest in vegans and lowest in meat-eaters.

- Elevated baseline urine glycine correlated with A1C (effect size >.8) in lean subjects, and with active IBD.

- Plasma glycine increased after two weeks of vitamin B6 depletion; serine increased.

- Lower blood glycine was associated with higher risk of metabolic disorders such as obesity, type 2 diabetes, and non-alcoholic fatty liver disease/liver fibrosis. Clinical studies have suggested beneficial effects with glycine supplementation.

- Lower urine glycine was associated with a higher decline of free T4 and a greater risk of hypothyroidism.

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Glycine is a nonessential amino acid that is synthesized from choline, serine, hydroxyproline, and threonine. It has many important physiologic functions. It is one of three amino acids that make up glutathione. Glycine’s dietary sources include meat, fish, legumes, and gelatins. Glycine is a major collagen and elastin component, which are the most abundant proteins in the body. Like taurine, it is an amino acid necessary for bile acid conjugation; therefore, it plays a key role in lipid digestion and absorption.

Glycine is the precursor to various important metabolites such as porphyrins, purines, heme, and creatine. It acts both as an inhibitory neurotransmitter in the CNS and as an excitatory neurotransmitter on N-methyl-D-aspartate (NMDA) receptors.

Glycine has anti-oxidant, anti-inflammatory, immunomodulatory, and cytoprotective roles in all tissues. In the folate cycle, glycine and serine are interconverted. These methyltransferase reactions and interconversions are readily reversible depending on the needs of the folate cycle to synthesize purines.

Glycine can also be generated from choline, betaine, dimethylglycine, and sarcosine within the methylation cycle itself. Glycine accepts a methyl group from S-adenosylmethionine (SAM) to form sarcosine. This conversion functions to control SAM excess.

Supplementation with glycine has been used to ameliorate metabolic disorders in patients with obesity, diabetes, cardiovascular disease, ischemia-reperfusion injuries, inflammatory diseases, and cancers.

Because of glycine’s excitatory effects on CNS NMDA receptors, research regarding the treatment of psychiatric disorders, such as schizophrenia, using glycine transport antagonists have shown great promise.

Oral glycine can boost tissue levels of glutathione, especially with concurrent NAC and/or lipoic acid. Because glutathione levels decline during the aging process, supplementing with glycine can impact elderly patients with low protein intake.

References:

- Edgar AJ. The human L-threonine 3-dehydrogenase gene is an expressed pseudogene. BMC Genet. 2002;3:18.

- Razak MA, Begum PS, Viswanath B, Rajagopal S. Multifarious Beneficial Effect of Nonessential Amino Acid, Glycine: A Review. Oxid Med Cell Longev. 2017;2017:1716701.

- Wang W, Wu Z, Dai Z, Yang Y, Wang J, Wu G. Glycine metabolism in animals and humans: implications for nutrition and health. Amino Acids. 2013;45(3):463-477.

- Hashimoto K. Glycine transporter inhibitors as therapeutic agents for schizophrenia. Recent Patents CNS Drug Discovery. 2006;1(1):43-53.

- Amelio I, Cutruzzolá F, Antonov A, Agostini M, Melino G. Serine and glycine metabolism in cancer. Trends Biochem Sci. 2014;39(4):191-198.

- Locasale JW. Serine, glycine and one-carbon units: cancer metabolism in full circle. Nat Rev Cancer. 2013;13(8):572.

- Beagle B, Yang TL, Hung J, Cogger EA, Moriarty DJ, Caudill MA. The glycine N-methyltransferase (GNMT) 1289 C→ T variant influences plasma total homocysteine concentrations in young women after restricting folate intake. J Nutr. 2005;135(12):2780-2785.

- McCarty MF, O’Keefe JH, DiNicolantonio JJ. Dietary Glycine Is Rate-Limiting for Glutathione Synthesis and May Have Broad Potential for Health Protection. Ochsner J. 2018;18(1):81-87.

- Pai YJ, Leung KY, Savery D, et al. Glycine decarboxylase deficiency causes neural tube defects and features of nonketotic hyperglycinemia in mice. Nat Comm. 2015;6:6388.

- Ebara S, Toyoshima S, Matsumura T, et al. Cobalamin deficiency results in severe metabolic disorder of serine and threonine in rats. Biochim Biophys Acta. 2001;1568(2):111- 117.

- Gould RL, Pazdro R. Impact of Supplementary Amino Acids, Micronutrients, and Overall Diet on Glutathione Homeostasis. Nutrients. 2019;11(5).

- Gropper S SJ, Groff J. Adv Nutr Human Metab. 5th ed. Belmont, CA: Wadsworth, Cengage Learning; 2009.

- Park YK, Linkswiler H. Effect of vitamin B6 depletion in adult man on the plasma concentration and the urinary excretion of free amino acids. JNutr. 1971;101(2):185-191.

- Lamers Y, Williamson J, Ralat M, et al. Moderate dietary vitamin B-6 restriction raises plasma glycine and cystathionine concentrations while minimally affecting the rates of glycine turnover and glycine cleavage in healthy men and women. J Nutr. 2009;139(3):452-460.