Glycine: Properties, Physiological Activities and Targets

General Description

Glycine, the smallest amino acid, is crucial for protein synthesis and various biological processes. It serves as a neurotransmitter, regulator of gene expression, and aids in motor function control. With physiological roles in pain modulation and protection against radiotherapy effects, glycine plays a diverse and essential part in maintaining health. It targets Glycine Receptors, ionotropic glutamate receptors, G protein-coupled receptors, and various transporters, showcasing its multifaceted involvement in neurotransmission and cellular activities. Overall, glycine's significance lies in its broad range of functions contributing to overall well-being and systemic balance.

Figure 1. Glycine

Properties

Chemical Structure and Composition

Glycine, also known as amino acetic acid, is a vital component of proteins and plays a crucial role in the synthesis of various biomolecules. It was first isolated in 1820 from gelatine through acid hydrolysis. The name "glycine" is derived from the Greek word glykys, meaning sweet, and it is the smallest amino acid with a molecular weight of 75.067 g/mol. Glycine can be found in both the hydrophilic and hydrophobic parts of the polypeptide chain. In the body, glycine is abundant in plasma, representing approximately 11.5% of the total amino acids and 20% of the nitrogen in body proteins. It accounts for 80% of the protein content. 

Chemical Structure and Composition

The recommended dietary intake of glycine is around 1.5-3 g/day. In young men, the average flux of glycine is about 34-35 mg/kg/h in the fed state, while in the post-absorptive state, it decreases to around 18 mg/kg/h. Approximately 35% of glycine in the body is synthesized endogenously. The average rate of de novo glycine synthesis is estimated to be 12-15 mg/kg/h, contributing to 81% of the systemic flux. The physiological concentration of glycine in plasma ranges from 200 to 300 mol/L. Overall, glycine is an essential amino acid involved in protein synthesis and the production of important biomolecules in the body. ¹

Physiological Activities

Neurotransmission Modulation

Glycine, an unessential amino acid for mammals, is crucial for various physiological activities. Synthesized endogenously by the body from serine, choline, threonine, and glyoxylate, it plays a multifaceted role in different systems. One of its key functions is as a neurotransmitter, where it modulates neuronal activity and inhibits various brain regions by binding to chloride-sensitive ion channels in the central nervous system (CNS). This inhibition of postsynaptic neurons is essential for normal neurological function. 

Pain Regulation

Moreover, glycine is involved in the mechanism of pain transmission. Its inhibition, either through pharmacological treatment or genetic deletion, can evoke pain hypersensitivity in living organisms, highlighting its importance in pain regulation. In addition to its neural roles, glycine also contributes to the control of motor functions. It has been shown to ameliorate motor deficiencies after surgery, indicating its potential in aiding motor function recovery. Furthermore, glycine plays a significant role in the regulation of gene expression, protein configuration, and various other biological functions. It acts as an antacid and modulates growth hormone synthesis, improving muscle tone, collagen synthesis, tissue restoration, and delaying muscular degeneration. Notably, glycine has been reported to protect the intestine against the harmful effects of radiotherapy in cancer treatment, showcasing its diverse protective properties. In conclusion, glycine's physiological activities encompass neurotransmission modulation, pain regulation, motor function control, gene expression regulation, and various protective and restorative functions, making it a vital component in maintaining overall health and well-being. ²

Targets

Glycine, as identified by the International Union of Basic and Clinical Pharmacology (IUPHAR), has multiple natural or endogenous targets. These include Glycine Receptors (GlyRs), which are comprised of various subunits such as α1, α2, α3, α4, and β. Additionally, glycine functions as a co-agonist for ionotropic glutamate receptors, specifically the subunits GluN1, GluN2A, GluN2B, GluN2C, and GluN2D. It also targets the G protein-coupled receptor family C group 6 (GPRC6). Furthermore, glycine is transported across lipid membranes by several transporters. These transporters include glycine transporter types 1 and 2 (GlyT1 and GlyT2), proton-coupled amino acid transporters 1 and 2, vesicular inhibitory amino acid transporter, neutral amino acid transporters (B0AT1, B0AT2, B0AT3, and NTT4), and sodium-coupled neutral amino acid transporters 1, 2, 4, and 5. These diverse targets reflect glycine's multifaceted role in neurotransmission and cellular function. ²

Reference

1. Tibbetts AS, Appling DR. Compartmentalization of Mammalian folate-mediated one-carbon metabolism. Annu Rev Nutr. 2010; 30: 57-81.

2. Aguayo-Cerón KA, Sánchez-Mu?oz F, Gutierrez-Rojas RA, et al. Glycine: The Smallest Anti-Inflammatory Micronutrient. Int J Mol Sci. 2023; 24(14): 11236.

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