Glycine is a simple, nonessential amino acid that in its pure form exists as a colorless, sweet-tasting crystalline solid. Glycine is the only achiral proteinogenic amino acid. While normally considered a non-essential amino acid, studies with rodent models show reduced growth on low-glycine diets. The average adult ingests 3 to 5 grams of glycine daily. Glycine is involved in the body's production of DNA, phospholipids and collagen, and in the production of energy. Glycine is biosynthesized in the body from the amino acid serine, which is in turn derived from 3-phosphoglycerate. In the liver, glycine synthesis is catalyzed by glycine synthase (also called glycine cleavage enzyme), which can produce glycine from ammonia, carbon dioxide, methylene tetrahydrofolate and NADH. Glycine is degraded via three pathways. With the most common pathway being called the glycine cleavage system. The glycine cleavage enzyme system comprises four proteins: P-, T-, H- and L-proteins (EC 1.4.4.2, EC 2.1.2.10 and EC 1.8.1.4 for P-, T- and L-proteins). Mutations have been described in the GLDC (OMIM 238300), AMT (OMIM 238310), and GCSH (OMIM 238330) genes encoding the P-, T-, and H-proteins respectively. The glycine cleavage system catalyzes the oxidative conversion of glycine into carbon dioxide and ammonia, with the remaining one-carbon unit transferred to folate as methylenetetrahydrofolate. The principal function of glycine is as a precursor to proteins. Most proteins incorporate only small quantities although collagen contains about 35% glycine. Glycine is also an inhibitory neurotransmitter in the central nervous system, especially in the spinal cord, brainstem, and retina. When glycine receptors are activated, chloride enters the neuron via ionotropic receptors, causing an Inhibitory postsynaptic potential (IPSP). There are a number of inborn errors of metabolism that are associated with elevated levels of glycine in the blood or urine. Nonketotic hyperglycinaemia (OMIM 606899) is an autosomal recessive condition caused by deficient enzyme activity of the glycine cleavage enzyme system (EC 2.1.1.10). It is the main catabolic pathway for glycine and it also contributes to one-carbon metabolism. Patients with a deficiency of this enzyme system have increased glycine in plasma, urine and cerebrospinal fluid (CSF) with an increased CSF: plasma glycine ratio (PMID 16151895). Glycine is also found to be associated with at least 12 other inborn errors of metabolism (IEMs) including: Citrullinemia Type I, Hyperglycinemia, non-ketotic, Hyperprolinemia Type I, Hyperprolinemia Type II, Iminoglycinuria, Isovaleric Aciduria, Malonic Aciduria, Methylmalonic Aciduria, Methylmalonic Aciduria Due to Cobalamin-Related Disorders, Non Ketotic Hyperglycinemeia, Prolinemia Type II, Propionic acidemia and Short Chain Acyl CoA Dehydrogenase Deficiency (SCAD Deficiency). When present in sufficiently high levels, glycine can be neurotoxin and a metabotoxin. A neurotoxin is a compound that disrupts or attacks neural tissue. A metabotoxin is an endogenously produced metabolite that causes adverse health effects at chronically high levels as found in many of the IEMs mentioned above. Glycine is known to act as a neurotransmitter. Chronically elevated levels of glycine can lead to a build-up of glycine in the brain, which leads to abnormal neural signaling and a condition known as glycine encephalopathy. Affected infants experience a progressive lack of energy (lethargy), feeding difficulties, weak muscle tone (hypotonia), abnormal jerking movements, and life-threatening problems with breathing. Most children who survive these early signs and symptoms develop profound intellectual disability and seizures. Other atypical types of glycine encephalopathy appear later in childhood or adulthood and cause a variety of medical problems that primarily affect the nervous system.