CSF Serine Enantiomers and Glycine in the Study of Neurologic and Psychiatric Disorders

Abstract

It was long believed that only the l-isomer of amino acids existed in mammals, and d–amino acids were regarded as laboratory artifacts and categorized as “unnatural” isomers. This term was widely used in textbooks of biochemistry. d–amino acids were known to be prominent in bacteria, and there were occasional reports of d–amino acids found in invertebrates (1). Hans Krebs accidentally discovered in kidney tissue an enzyme, d–amino acid oxidase (DAAO)1 , which recognized unnatural d–amino acids (but not their l-counterparts) (2). DAAO was found to degrade d–amino acids produced by bacteria from foods in the gut. With the advance of chromatographic analysis techniques, small amounts of d–amino acids can now be measured in lower and higher animals, plants, and foods. By the use of 2-dimensional thin-layer chromatography and HPLC, Nagata et al. (3) found free d–amino acids, including d-serine, in kidney and blood of mutant mice lacking DAAO. Subsequently, Hashimoto and colleagues (4) demonstrated that d-serine was present in rat brain at high concentrations that were up to one-third those of l-serine, and that d-serine is heterogeneously distributed throughout rat brain with a …