Glycine, Serine and Threonine Metabolism

This pathway describes the synthesis and breakdown of a number of small amino acids, including glycine, serine, threonine and cysteine. All of these compounds share common intermediates and almost all can be biosynthesized from one another. As an essential amino acid, threonine is not synthesized in humans and must be obtained from either the diet or from intestinal microflora. Threonine can be metabolized in two ways, it can be converted to pyruvate or to alpha-ketobutyrate. In particular, threonine can be converted to pyruvate via threonine dehydrogenase. An intermediate in this pathway can undergo thiolysis with CoA to produce acetyl-CoA and glycine. In humans, threonine is converted to alpha-ketobutyrate in a less common pathway via serine dehydratase, and thereby enters the pathway leading to succinyl-CoA. Serine and glycine are not essential amino acids and can be synthesized not only from threonine, but from a number of other routes. For example, serine can be synthesized via glycerate, which can be converted to glycerate 3-phosphate (via glycerate kinase), which in turn is converted to phosphohydroxypyruvate and then phosphoserine and finally serine. The serine synthesized via this route, can create cysteine and glycine through the homocysteine cycle. Cystathionine beta-synthase catalyses the condensation of homocysteine and serine to give cystathionine. Cystathionine beta-lyase then converts this double amino acid to cysteine, ammonia, and α-ketoglutarate. Serine can also be used in polypeptide synthesis (via Seryl-tRNA synthetase) or in glyoxylate metabolism (via conversion to hydroxypyruvate) or in phosphatidylserine synthesis. Glycine is biosynthesized in the body from the amino acid serine. In most organisms, the enzyme serine hydroxymethyltransferase catalyses this transformation using tetrahydrofolate (THF), leading to methylene THF and glycine. In the liver of vertebrates, glycine synthesis is catalyzed by glycine synthase (also called glycine cleavage enzyme) in which carbon dioxide and ammonia combine with methylene THF to produce glycine and tetrahydrofolate. The cofactor NADH is oxidzed in this process. Glycine can be degraded via three pathways. The predominant pathway in animals involves the reverse of the reaction catalyzed by glycine synthase. This leads to the degradation of glycine into ammonia and CO2. In the second pathway, glycine is degraded in two steps. The first step is the reverse of glycine biosynthesis from serine with serine hydroxymethyl transferase. Serine is then converted to pyruvate by serine dehydratase. In the third route to glycine degradation, glycine is converted to glyoxylate by D-amino acid oxidase. Glyoxylate is then oxidized by hepatic lactate dehydrogenase to oxalate in an NAD+-dependent reaction. Glycine also functions as an inhibitory neurotransmitter in the central nervous system.

References

1. Lehninger, A.L. (2005) Lehninger principles of biochemistry (4 ^th ed.). New York: W.H Freeman.
2. Salway, J.G. (2004) Metabolism at a glance (3 ^rd ed.). Alden, Mass. : Blackwell Pub.