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Since biosynthesis of\n                    <jats:sc>l<\/jats:sc>\n                    \u2010glutamate and \u03b3\u2010aminobutyric acid (GABA) requires 2\u2010oxoglutarate while 3\u2010phosphoglycerate is the precursor of\n                    <jats:sc>l<\/jats:sc>\n                    \u2010glycine and\n                    <jats:sc>d<\/jats:sc>\n                    \u2010serine, evolutionary selection of these amino acid neurotransmitters might have been driven by their capacity to provide important information about the glycolytic pathway and Krebs cycle. Synthesis and recycling of amino acid neurotransmitters as well as composition and function of their receptors are often compromised in inherited metabolic diseases. For instance, increased plasma\n                    <jats:sc>l<\/jats:sc>\n                    \u2010phenylalanine concentrations impair cerebral biosynthesis of protein and bioamines in phenylketonuria, while elevated cerebral\n                    <jats:sc>l<\/jats:sc>\n                    \u2010phenylalanine directly acts via ionotropic glutamate receptors. In succinic semialdehyde dehydrogenase deficiency, the neurotransmitter GABA and neuromodulatory \u03b3\u2010hydroxybutyric acid are elevated. Chronic hyperGABAergic state results in progressive downregulation of GABA\n                    <jats:sub>A<\/jats:sub>\n                    and GABA\n                    <jats:sub>B<\/jats:sub>\n                    receptors and impaired mitophagy. In glycine encephalopathy, the neurological phenotype is precipitated by\n                    <jats:sc>l<\/jats:sc>\n                    \u2010glycine acting both via cortical NMDA receptors and glycine receptors in spinal cord and brain stem neurons. Serine deficiency syndromes are biochemically characterized by decreased biosynthesis of\n                    <jats:sc>l<\/jats:sc>\n                    \u2010serine, an important neurotrophic factor, and the neurotransmitters\n                    <jats:sc>d<\/jats:sc>\n                    \u2010serine and\n                    <jats:sc>l<\/jats:sc>\n                    \u2010glycine. Supplementation with\n                    <jats:sc>l<\/jats:sc>\n                    \u2010serine and\n                    <jats:sc>l<\/jats:sc>\n                    \u2010glycine has a positive effect on seizure frequency and spasticity, while neurocognitive development can only be improved if treatment starts in utero or immediately postnatally. With novel techniques, the study of synaptic dysfunction in inherited metabolic diseases has become an emerging research field. More and better therapies are needed for these difficult\u2010to\u2010treat diseases.\n                  <\/jats:p>","DOI":"10.1007\/s10545-018-0201-4","type":"journal-article","created":{"date-parts":[[2018,6,4]],"date-time":"2018-06-04T12:15:35Z","timestamp":1528114535000},"page":"1055-1063","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["Metabolism of amino acid neurotransmitters: the synaptic disorder underlying inherited metabolic diseases"],"prefix":"10.1002","volume":"41","author":[{"given":"Stefan","family":"K\u00f6lker","sequence":"first","affiliation":[{"name":"Division of Pediatric Neurology and Metabolic Medicine, Centre for Pediatric and Adolescent Medicine University Hospital Heidelberg Im Neuenheimer Feld 430 Heidelberg 69120 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