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2 Serine, Glycine, and Threonine

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Handbook of Neurochemistry and Molecular Neurobiology

Abstract:

Amino acids are not only indispensable for protein synthesis but also play important cellular functions. In this chapter, the central nervous system (CNS) functions of serine, glycine, and threonine are discussed. Both the specific functions of the aforementioned amino acids and the functions of their derivatives are reviewed in relation to brain development and neurotransmission. In particular, for serine and glycine exciting new functions were unravelled recently.

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Abbreviations

CNS:

central nervous system

GCS:

glycine cleavage system

SHMTs:

serine hydroxymethyltransferases

3-PGDH:

3-phosphoglycerate dehydrogenase

5,10-MTHF:

5,10-methylenetetrahydrofolate

mSHMT:

mitochondrial isoenzyme

cSHMT:

cytosolic isoenzyme

SAM:

S-adenosylmethionine

HSN I:

hereditary sensory neuropathy type I

GlyT1:

glycine transporter subtype 1

EDG:

endothelial differentiation gene

AMPA:

2-amino-3-hydroxy-5-methyl-4-isoxazolepropionate

MRI:

magnetic resonance imaging

CSF:

cerebrospinal fluid

3-PSP:

3-phosphoserine phosphatase

DAO:

d-amino acid oxidase

VIAAT:

vesicular inhibitory amino acid transporter

NKH:

nonketotic hyperglycinemia

PLP:

pyridoxal phosphate

ALS:

amyotrophic lateral sclerosis

GRs:

glycine receptors

References

  • Achouri Y, Rider MH, Schaftingen EV, Robbi M. 1997. Cloning, sequencing and expression of rat liver 3-phosphoglycerate dehydrogenase. Biochem J 323: 365–370.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Achouri Y, Robbi M, Van Schaftingen E. 1999. Role of cysteine in the dietary control of the expression of 3-phosphoglycerate dehydrogenase in rat liver. Biochem J 344: 15–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Aliefendioglu D, Tana Aslan A, Coskun T, Dursun A, Cakmak FN, et al. 2003. Transient nonketotic hyperglycinemia: Two case reports and literature review. Pediatr Neurol 28: 151–155.

    Article  PubMed  Google Scholar 

  • Applegarth DA, Toone JR. 2004. Glycine encephalopathy (nonketotic hyperglycinaemia): Review and update. J Inherit Metab Dis 27: 417–422.

    Article  CAS  PubMed  Google Scholar 

  • Aprison MH, Shank RP, Davidoff RA. 1969. A comparison of the concentration of glycine, a transmitter suspect, in different areas of the brain and spinal cord in seven different vertebrates. Comp Biochem Physiol 28: 1345–1355.

    Article  CAS  PubMed  Google Scholar 

  • Aragon C, Lopez-Corcuera B. 2003. Structure, function and regulation of glycine neurotransporters. Eur J Pharmacol 479: 249–262.

    Article  CAS  PubMed  Google Scholar 

  • Armano S, Coco S, Bacci A, Pravettoni E, Schenk U, et al. 2002. Localization and functional relevance of system A neutral amino acid transporters in cultured hippocampal neurons. J Biol Chem 277: 10467–10473.

    Article  CAS  PubMed  Google Scholar 

  • Bakker MJ, van Dijk JG, van den Maagdenberg AM, Tijssen MA. 2006. Startle syndromes. Lancet Neurol 5: 513–524.

    Article  PubMed  Google Scholar 

  • Bejaoui K, Wu C, Scheffler MD, Haan G, Ashby P, et al. 2001. SPTLC1 is mutated in hereditary sensory neuropathy, type 1. Nat Genet 27: 261–262.

    Article  CAS  PubMed  Google Scholar 

  • Benitez-Diaz P, Miranda-Contreras L, Mendoza-Briceno RV, Pena-Contreras Z, Palacios-Pru E. 2003. Prenatal and postnatal contents of amino acid neurotransmitters in mouse parietal cortex. Dev Neurosci 25: 366–374.

    Article  CAS  PubMed  Google Scholar 

  • Betz H, Kuhse J, Schmieden V, Laube B, Kirsch J, et al. 1999. Structure and functions of inhibitory and excitatory glycine receptors. Ann N Y Acad Sci 868: 667–676.

    Article  CAS  PubMed  Google Scholar 

  • Boehm G, Cervantes H, Georgi G, Jelinek J, Sawatzki G, et al. 1998. Effect of increasing dietary threonine intakes on amino acid metabolism of the central nervous system and peripheral tissues in growing rats. Pediatr Res 44: 900–906.

    Article  CAS  PubMed  Google Scholar 

  • Brody SA, Nakanishi N, Tu S, Lipton SA, Geyer MA. 2005. A developmental influence of the N-methyl-d-aspartate receptor NR3A subunit on prepulse inhibition of startle. Biol Psychiatry 57: 1147–1152.

    Article  CAS  PubMed  Google Scholar 

  • Casamenti F, Scali C, Pepeu G. 1991. Phosphatidylserine reverses the age-dependent decrease in cortical acetylcholine release: A microdialysis study. Eur J Pharmacol 194: 11–16.

    Article  CAS  PubMed  Google Scholar 

  • Castagne V, Maire JC, Gyger M. 1996. Neurotoxicology and amino acid intake during development: The case of threonine. Pharmacol Biochem Behav 55: 653–662.

    Article  CAS  PubMed  Google Scholar 

  • Cetin I, Fennessey PV, Sparks JW, Meschia G, Battaglia FC. 1992. Fetal serine fluxes across fetal liver, hindlimb, and placenta in late gestation. Am J Physiol 263: E786–E793.

    CAS  PubMed  Google Scholar 

  • Cetin I, Marconi AM, Baggiani AM, Buscaglia M, Pardi G, et al. 1995. In vivo placental transport of glycine and leucine in human pregnancies. Pediatr Res 37: 571–575.

    Article  CAS  PubMed  Google Scholar 

  • Chatterton JE, Awobuluyi M, Premkumar LS, Takahashi H, Talantova M, et al. 2002. Excitatory glycine receptors containing the NR3 family of NMDA receptor subunits. Nature 415: 793–798.

    Article  CAS  PubMed  Google Scholar 

  • Christensen H, Fonnum F. 1991. Uptake of glycine, GABA and glutamate by synaptic vesicles isolated from different regions of rat CNS. Neurosci Lett 129: 217–220.

    Article  CAS  PubMed  Google Scholar 

  • Chumakov I, Blumenfeld M, Guerassimenko O, Cavarec L, Palicio M, et al. 2002. Genetic and physiological data implicating the new human gene G72 and the gene for d-amino acid oxidase in schizophrenia. Proc Natl Acad Sci USA 99: 13675–13680.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Clayton PT, Surtees RA, De Vile C, Hyland K, Heales SJ. 2003. Neonatal epileptic encephalopathy. Lancet 361: 1614.

    Article  CAS  PubMed  Google Scholar 

  • Colombaioni L, Garcia-Gil M. 2004. Sphingolipid metabolites in neural signalling and function. Brain Res Brain Res Rev 46: 328–355.

    Article  CAS  PubMed  Google Scholar 

  • Cubelos B, Gimenez C, Zafra F. 2005. Localization of the GLYT1 glycine transporter at glutamatergic synapses in the rat brain. Cereb Cortex 15: 448–459.

    Article  PubMed  Google Scholar 

  • Daly EC, Aprison MH. 1974. Distribution of serine hydroxymethyltransferase and glycine transaminase in several areas of the central nervous system of the rat. J Neurochem 22: 877–885.

    Article  CAS  PubMed  Google Scholar 

  • Daly EC, Nadi NS, Aprison MH. 1976. Regional distribution and properties of the glycine cleavage system within the central nervous system of the rat: Evidence for an endogenous inhibitor during in vitro assay. J Neurochem 26: 179–185.

    CAS  PubMed  Google Scholar 

  • de Koning TJ, Duran M, Dorland L, Gooskens R, Van Schaftingen E, Jaeken J, Blau N, Berger R, Poll-The BT. 1998. Beneficial effects of l-serine and glycine in the management of seizures in 3-phosphoglycerate dehydrogenase deficiency. Ann Neurol 44: 261–265.

    Article  CAS  PubMed  Google Scholar 

  • de Koning TJ, Klomp LW. 2004. Serine-deficiency syndromes. Curr Opin Neurol 17: 197–204.

    Article  CAS  PubMed  Google Scholar 

  • de Koning TJ, Klomp LW, van Oppen AC, Beemer FA, Dorland L, et al. 2004. Prenatal and early postnatal treatment in 3-phosphoglycerate-dehydrogenase deficiency. Lancet 364: 2221–2222.

    Article  CAS  PubMed  Google Scholar 

  • de Koning TJ, Klomp LW, van Oppen AC, Beemer FA, Dorland L, et al. 2004. Prenatal and early postnatal treatment in 3-phosphoglycerate-dehydrogenase deficiency. Lancet 364: 2221–2222.

    Article  CAS  PubMed  Google Scholar 

  • Dringen R, Verleysdonk S, Hamprecht B, Willker W, Leibfritz D, et al. 1998. Metabolism of glycine in primary astroglial cells: Synthesis of creatine, serine, and glutathione. J Neurochem 70: 835–840.

    Article  CAS  PubMed  Google Scholar 

  • Edgar AJ. 2002. The human l-threonine 3-dehydrogenase gene is an expressed pseudogene. BMC Genet 3: 18.

    Article  PubMed  PubMed Central  Google Scholar 

  • Edgar AJ. 2005. Mice have a transcribed l-threonine aldolase/GLY1 gene, but the human GLY1 gene is a non-processed pseudogene. BMC Genomics 6: 32.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Edgar AJ, Polak JM. 2000. Molecular cloning of the human and murine 2-amino-3-ketobutyrate coenzyme A ligase cDNAs. Eur J Biochem 267: 1805–1812.

    Article  CAS  PubMed  Google Scholar 

  • Eulenburg V, Armsen W, Betz H, Gomeza J. 2005. Glycine transporters: Essential regulators of neurotransmission. Trends Biochem Sci 30: 325–333.

    Article  CAS  PubMed  Google Scholar 

  • Flint AC, Liu X, Kriegstein AR. 1998. Nonsynaptic glycine receptor activation during early neocortical development. Neuron 20: 43–53.

    Article  CAS  PubMed  Google Scholar 

  • Fu TF, Rife JP, Schirch V. 2001. The role of serine hydroxymethyltransferase isozymes in one-carbon metabolism in MCF-7 cells as determined by 13C NMR. Arch Biochem Biophys 393: 42–50.

    Article  CAS  PubMed  Google Scholar 

  • Fuchs SA, Berger R, Klomp LW, de Koning TJ. 2005. d-Amino acids in the central nervous system in health and disease. Mol Genet Metab 85: 168–180.

    Article  CAS  PubMed  Google Scholar 

  • Furuya S, Mitoma J, Makino A, Hirabayashi Y. 1998. Ceramide and its interconvertible metabolite sphingosine function as indispensable lipid factors involved in survival and dendritic differentiation of cerebellar Purkinje cells. J Neurochem 71: 366–377.

    Article  CAS  PubMed  Google Scholar 

  • Furuya S, Tabata T, Mitoma J, Yamada K, Yamasaki M, et al. 2000. l-Serine and glycine serve as major astroglia-derived trophic factors for cerebellar Purkinje neurons. Proc Natl Acad Sci USA 97: 11528–11533.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gomeza J, Hulsmann S, Ohno K, Eulenburg V, Szoke K, et al. 2003a. Inactivation of the glycine transporter 1 gene discloses vital role of glial glycine uptake in glycinergic inhibition. Neuron 40: 785–796.

    Article  CAS  PubMed  Google Scholar 

  • Gomeza J, Ohno K, Hulsmann S, Armsen W, Eulenburg V, et al. 2003b. Deletion of the mouse glycine transporter 2 results in a hyperekplexia phenotype and postnatal lethality. Neuron 40: 797–806.

    Article  CAS  PubMed  Google Scholar 

  • Growdon JH, Nader TM, Schoenfeld J, Wurtman RJ. 1991. l-Threonine in the treatment of spasticity. Clin Neuropharmacol 14: 403–412.

    Article  CAS  PubMed  Google Scholar 

  • Gundersen RY, Vaagenes P, Breivik T, Fonnum F, Opstad PK. 2005. Glycine—an important neurotransmitter and cytoprotective agent. Acta Anaesthesiol Scand 49: 1108–1116.

    Article  CAS  PubMed  Google Scholar 

  • Hao S, Sharp JW, Ross-Inta CM, McDaniel BJ, Anthony TG, et al. 2005. Uncharged tRNA and sensing of amino acid deficiency in mammalian piriform cortex. Science 307: 1776–1778.

    Article  CAS  PubMed  Google Scholar 

  • Hashimoto A, Kumashiro S, Nishikawa T, Oka T, Takahashi K, et al. 1993a. Embryonic development and postnatal changes in free d-aspartate and d-serine in the human prefrontal cortex. J Neurochem 61: 348–351.

    Article  CAS  PubMed  Google Scholar 

  • Hashimoto A, Nishikawa T, Oka T, Takahashi K. 1993b. Endogenous d-serine in rat brain: N-methyl-d-aspartate receptor-related distribution and aging. J Neurochem 60: 783–786.

    Article  CAS  PubMed  Google Scholar 

  • Hashimoto K, Engberg G, Shimizu E, Nordin C, Lindstrom LH, et al. 2005. Reduced d-serine to total serine ratio in the cerebrospinal fluid of drug naïve schizophrenic patients. Prog Neuropsychopharmacol Biol Psychiatry 29: 767–769.

    Article  CAS  PubMed  Google Scholar 

  • Hashimoto K, Fukushima T, Shimizu E, Komatsu N, Watanabe H, et al. 2003. Decreased serum levels of d-serine in patients with schizophrenia: Evidence in support of the N-methyl-d-aspartate receptor hypofunction hypothesis of schizophrenia. Arch Gen Psychiatry 60: 572–576.

    Article  CAS  PubMed  Google Scholar 

  • Hayasaka S, Hara S, Mizuno K, Narisawa K, Tada K. 1986. Leber's congenital amaurosis associated with hyperthreoninemia. Am J Ophthalmol 101: 475–479.

    Article  CAS  PubMed  Google Scholar 

  • Helboe L, Egebjerg J, Moller M, Thomsen C. 2003. Distribution and pharmacology of alanine-serine-cysteine transporter 1 (asc-1) in rodent brain. Eur J Neurosci 18: 2227–2238.

    Article  PubMed  Google Scholar 

  • Herbig K, Chiang EP, Lee LR, Hills J, Shane B, et al. 2002. Cytoplasmic serine hydroxymethyltransferase mediates competition between folate-dependent deoxyribonucleotide and S-adenosylmethionine biosyntheses. J Biol Chem 277: 38381–38389.

    Article  CAS  PubMed  Google Scholar 

  • Hoover-Fong JE, Shah S, Van Hove JL, Applegarth D, Toone J, et al. 2004. Natural history of nonketotic hyperglycinemia in 65 patients. Neurology 63: 1847–1853.

    Article  CAS  PubMed  Google Scholar 

  • Huether G, Lajtha A. 1991. Changes in free amino acid concentrations in serum, brain, and CSF throughout embryogenesis. Neurochem Res 16: 145–150.

    Article  CAS  PubMed  Google Scholar 

  • Ikonomidou C, Bosch F, Miksa M, Bittigau P, Vockler J, et al. 1999. Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain. Science 283: 70–74.

    Article  CAS  PubMed  Google Scholar 

  • Jaeken J, Detheux M, Fryns JP, Collet JF, Alliet P, et al. 1997. Phosphoserine phosphatase deficiency in a patient with Williams syndrome. J Med Genet 34: 594–596.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kartvelishvily E, Shleper M, Balan L, Dumin E, Wolosker H. 2006. Neuron-derived d-serine release provides a novel means to activate N-methyl-d-aspartate receptors. J Biol Chem 281: 14151–14162.

    Article  CAS  PubMed  Google Scholar 

  • Klomp LW, de Koning TJ, Malingre HE, van Beurden EA, Brink M, et al. 2000. Molecular characterization of 3-phosphoglycerate dehydrogenase deficiency—a neurometabolic disorder associated with reduced l-serine biosynthesis. Am J Hum Genet 67: 1389–1399.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kuge O, Nishijima M. 1997. Phosphatidylserine synthase I and II of mammalian cells. Biochim Biophys Acta 1348: 151–156.

    Article  CAS  PubMed  Google Scholar 

  • Lee A, Patterson V. 1993. A double-blind study of l-threonine in patients with spinal spasticity. Acta Neurol Scand 88: 334–338.

    Article  CAS  PubMed  Google Scholar 

  • Legendre P. 2001. The glycinergic inhibitory synapse. Cell Mol Life Sci 58: 760–793.

    Article  CAS  PubMed  Google Scholar 

  • Lewis RM, Godfrey KM, Jackson AA, Cameron IT, Hanson MA. 2005. Low serine hydroxymethyltransferase activity in the human placenta has important implications for fetal glycine supply. J Clin Endocrinol Metab 90: 1594–1598.

    Article  CAS  PubMed  Google Scholar 

  • Lowry M, Hall DE, Hall MS, Brosnan JT. 1987. Renal metabolism of amino acids in vivo: Studies on serine and glycine fluxes. Am J Physiol 252: F304–F309.

    CAS  PubMed  Google Scholar 

  • Luberto C, Kraveka JM, Hannun YA. 2002. Ceramide regulation of apoptosis versus differentiation: A walk on a fine line. Lessons from neurobiology. Neurochem Res 27: 609–617.

    Article  CAS  PubMed  Google Scholar 

  • Luka Z, Cerone R, Phillips JA, Mudd HS, Wagner C. 2002. Mutations in human glycine N-methyltransferase give insights into its role in methionine metabolism. Hum Genet 110: 68–74.

    Article  CAS  PubMed  Google Scholar 

  • Lynch JW. 2004. Molecular structure and function of the glycine receptor chloride channel. Physiol Rev 84: 1051–1095.

    Article  CAS  PubMed  Google Scholar 

  • Matsuo H, Kanai Y, Tokunaga M, Nakata T, Chairoungdua A, et al. 2004. High affinity d- and l-serine transporter Asc-1: Cloning and dendritic localization in the rat cerebral and cerebellar cortices. Neurosci Lett 358: 123–126.

    Article  CAS  PubMed  Google Scholar 

  • McDaniel MA, Maier SF, Einstein GO. 2003. “Brain-specific” nutrients: A memory cure? Nutrition 19: 957–975.

    Article  CAS  PubMed  Google Scholar 

  • Mills PB, Surtees RA, Champion MP, Beesley CE, Dalton N, et al. 2005. Neonatal epileptic encephalopathy caused by mutations in the PNPO gene encoding pyridox(am)ine 5′-phosphate oxidase. Hum Mol Genet 14: 1077–1086.

    Article  CAS  PubMed  Google Scholar 

  • Mitoma J, Furuya S, Hirabayashi Y. 1998a. A novel metabolic communication between neurons and astrocytes: Non-essential amino acid l-serine released from astrocytes is essential for developing hippocampal neurons. Neurosci Res 30: 195–199.

    Article  CAS  PubMed  Google Scholar 

  • Mitoma J, Ito M, Furuya S, Hirabayashi Y. 1998b. Bipotential roles of ceramide in the growth of hippocampal neurons: Promotion of cell survival and dendritic outgrowth in dose- and developmental stage-dependent manners. J Neurosci Res 51: 712–722.

    Article  CAS  PubMed  Google Scholar 

  • Mitoma J, Kasama T, Furuya S, Hirabayashi Y. 1998c. Occurrence of an unusual phospholipid, phosphatidyl-l-threonine, in cultured hippocampal neurons. Exogenous l-serine is required for the synthesis of neuronal phosphatidyl-l-serine and sphingolipids. J Biol Chem 273: 19363–19366.

    Article  CAS  PubMed  Google Scholar 

  • Moores RR, Rietberg CC, Battaglia FC, Fennessey PV, Meschia G. 1993. Metabolism and transport of maternal serine by the ovine placenta: Glycine production and absence of serine transport into the fetus. Pediatr Res 33: 590–594.

    Article  CAS  PubMed  Google Scholar 

  • Mori M, Gähwiler BH, Gerber U. 2002. β-Alanine and taurine as endogenous agonists at glycine receptors in rat hippocampus in vitro. J Physiol 539: 191–200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nagata Y, Horiike K, Maeda T. 1994. Distribution of free d-serine in vertebrate brains. Brain Res 634: 291–295.

    Article  CAS  PubMed  Google Scholar 

  • Narkewicz MR, Thureen PJ, Sauls SD, Tjoa S, Nikolayevsky N, et al. 1996. Serine and glycine metabolism in hepatocytes from mid gestation fetal lambs. Pediatr Res 39: 1085–1090.

    Article  CAS  PubMed  Google Scholar 

  • Nguyen L, Malgrange B, Belachew S, Rogister B, Rocher V, et al. 2002. Functional glycine receptors are expressed by postnatal nestin-positive neural stem/progenitor cells. Eur J Neurosci 15: 1299–1305.

    Article  PubMed  Google Scholar 

  • Nong Y, Huang YQ, Ju W, Kalia LV, Ahmadian G, et al. 2003. Glycine binding primes NMDA receptor internalization. Nature 422: 302–307.

    Article  CAS  PubMed  Google Scholar 

  • Parton M, Mitsumoto H, Leigh PN. 2003. Amino acids for amyotrophic lateral sclerosis/motor neuron disease. Cochrane Database Syst Rev 4: CD003457.

    Google Scholar 

  • Quackenbush EJ, Kraemer KH, Gahl WA, Schirch V, Whiteman DA, et al. 1999. Hypoglycinaemia and psychomotor delay in a child with xeroderma pigmentosum. J Inherit Metab Dis 22: 915–924.

    Article  CAS  PubMed  Google Scholar 

  • Reddi OS. 1978. Threoninemia—a new metabolic defect. J Pediatr 93: 814–816.

    Article  CAS  PubMed  Google Scholar 

  • Rees MI, Harvey K, Pearce BR, Chung SK, Duguid IC, et al. 2006. Mutations in the gene encoding GlyT2 (SLC6A5) define a presynaptic component of human startle disease. Nat Genet 38: 801–806.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ristoff E, Mayatepek E, Larsson A. 2001. Long-term clinical outcome in patients with glutathione synthetase deficiency. J Pediatr 139: 79–84.

    Article  CAS  PubMed  Google Scholar 

  • Sakai K, Shimizu H, Koike T, Furuya S, Watanabe M. 2003. Neutral amino acid transporter ASCT1 is preferentially expressed in l-Ser-synthetic/storing glial cells in the mouse brain with transient expression in developing capillaries. J Neurosci 23: 550–560.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Savoca R, Ziegler U, Sonderegger P. 1995. Effects of l-serine on neurons in vitro. J Neurosci Methods 61: 159–167.

    Article  CAS  PubMed  Google Scholar 

  • Schell MJ, Brady RO, Molliver ME, Snyder SH. 1997. d-Serine as a neuromodulator: Regional and developmental localizations in rat brain glia resemble NMDA receptors. J Neurosci 17: 1604–1615.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schell MJ, Molliver ME, Snyder SH. 1995. d-Serine, an endogenous synaptic modulator: Localization to astrocytes and glutamate-stimulated release. Proc Natl Acad Sci USA 92: 3948–3952.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schulze A. 2003. Creatine deficiency syndromes. Mol Cell Biochem 244: 143–150.

    Article  CAS  PubMed  Google Scholar 

  • Shank RP, Aprison MH. 1970. The metabolism in vivo of glycine and serine in eight areas of the rat central nervous system. J Neurochem 17: 1461–1475.

    Article  CAS  PubMed  Google Scholar 

  • Shiang R, Ryan SG, Zhu YZ, Hahn AF, O'Connell P, et al. 1993. Mutations in the α1 subunit of the inhibitory glycine receptor cause the dominant neurologic disorder, hyperekplexia. Nat Genet 5: 351–358.

    Article  CAS  PubMed  Google Scholar 

  • Smith QR, Momma S, Aoyagi M, Rapoport SI. 1987. Kinetics of neutral amino acid transport across the blood–brain barrier. J Neurochem 49: 1651–1658.

    Article  CAS  PubMed  Google Scholar 

  • Snell K. 1984. Enzymes of serine metabolism in normal, developing and neoplastic rat tissues. Adv Enzyme Regul 22: 325–400.

    Article  CAS  PubMed  Google Scholar 

  • Snyder SH, Kim PM. 2000. d-Amino acids as putative neurotransmitters: Focus on d-serine. Neurochem Res 25: 553–560.

    Article  CAS  PubMed  Google Scholar 

  • Stein V, Nicoll RA. 2003. GABA generates excitement. Neuron 37: 375–378.

    Article  CAS  PubMed  Google Scholar 

  • Sugiura N, Patel RG, Corriveau RA. 2001. N-Methyl-d-aspartate receptors regulate a group of transiently expressed genes in the developing brain. J Biol Chem 276: 14257–14263.

    Article  CAS  PubMed  Google Scholar 

  • Tapia JC, Mentis GZ, Navarrete R, Nualart F, Figueroa E, et al. 2001. Early expression of glycine and GABAA receptors in developing spinal cord neurons. Effects on neurite outgrowth. Neuroscience 108: 493–506.

    CAS  PubMed  Google Scholar 

  • Tsai G, Coyle JT. 2002. Glutamatergic mechanisms in schizophrenia. Annu Rev Pharmacol Toxicol 42: 165–179.

    Article  CAS  PubMed  Google Scholar 

  • Tuominen HJ, Tiihonen J, Wahlbeck K. 2005. Glutamatergic drugs for schizophrenia: A systematic review and meta-analysis. Schizophr Res 72: 225–234.

    Article  PubMed  Google Scholar 

  • Tuominen HJ, Tiihonen J, Wahlbeck K. 2006. Glutamatergic drugs for schizophrenia. Cochrane Database Syst Rev 19: CD003730.

    Google Scholar 

  • Tyurina YY, Shvedova AA, Kawai K, Tyurin VA, Kommineni C, et al. 2000. Phospholipid signaling in apoptosis: Peroxidation and externalization of phosphatidylserine. Toxicology 148: 93–101.

    Article  CAS  PubMed  Google Scholar 

  • van der Knaap MS, Wevers RA, Kure S, Gabreels FJ, Verhoeven NM, et al. 1999. Increased cerebrospinal fluid glycine: A biochemical marker for a leukoencephalopathy with vanishing white matter. J Child Neurol 14: 728–731.

    Article  CAS  PubMed  Google Scholar 

  • Veiga-da-Cunha M, Collet JF, Prieur B, Jaeken J, Peeraer Y, et al. 2004. Mutations responsible for 3-phosphoserine phosphatase deficiency. Eur J Hum Genet 12: 163–166.

    Article  CAS  PubMed  Google Scholar 

  • Verleysdonk S, Martin H, Willker W, Leibfritz D, Hamprecht B. 1999. Rapid uptake and degradation of glycine by astroglial cells in culture: Synthesis and release of serine and lactate. Glia 27: 239–248.

    Article  CAS  PubMed  Google Scholar 

  • Wang LZ, Zhu XZ. 2003. Spatiotemporal relationships among d-serine, serine racemase, and d-amino acid oxidase during mouse postnatal development. Acta Pharmacol Sin 24: 965–974.

    CAS  PubMed  Google Scholar 

  • Wolosker H, Sheth KN, Takahashi M, Mothet JP, Brady RO Jr, et al. 1999. Purification of serine racemase: Biosynthesis of the neuromodulator d-serine. Proc Natl Acad Sci USA 96: 721–725.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xie X, Dumas T, Tang L, Brennan T, Reeder T, et al. 2005. Lack of the alanine-serine-cysteine transporter 1 causes tremors, seizures, and early postnatal death in mice. Brain Res 1052: 212–221.

    Article  CAS  PubMed  Google Scholar 

  • Yamamoto T, Nishizaki I, Furuya S, Hirabayashi Y, Takahashi K, et al. 2003. Characterization of rapid and high-affinity uptake of l-serine in neurons and astrocytes in primary culture. FEBS Lett 548: 69–73.

    Article  CAS  PubMed  Google Scholar 

  • Yamasaki M, Yamada K, Furuya S, Mitoma J, Hirabayashi Y, et al. 2001. 3-Phosphoglycerate dehydrogenase, a key enzyme for l-serine biosynthesis, is preferentially expressed in the radial glia/astrocyte lineage and olfactory ensheathing glia in the mouse brain. J Neurosci 21: 7691–7704.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yoshida K, Furuya S, Osuka S, Mitoma J, Shinoda Y, et al. 2004. Targeted disruption of the mouse 3-phosphoglycerate dehydrogenase gene causes severe neurodevelopmental defects and results in embryonic lethality. J Biol Chem 279: 3573–3577.

    Article  CAS  PubMed  Google Scholar 

  • Zafra F, Aragon C, Olivares L Danbolt NC, Gimenez C, et al. 1995. Glycine transporters are differentially expressed among CNS cells. J Neurosci 15: 3952–3969.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zwaal RF, Comfurius P, Bevers EM. 2004. Scott syndrome, a bleeding disorder caused by defective scrambling of membrane phospholipids. Biochim Biophys Acta 1636: 119–128.

    Article  CAS  PubMed  Google Scholar 

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Authors
  1. T. J. de Koning
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  2. S. A. Fuchs
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  3. L. W. J. Klomp
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  1. Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, 10962, Orangeburg, New york, USA

    Abel Lajtha (Director) (Director)

  2. The Centre for Laboratory Medicine, Tampere University Hospital, PB 2000, FI-33520, Tampere, Finland

    Simo S. Oja

  3. Inst. for Pharmacology, Royal Danish School of Pharmacy, Universitetsparken 2, DK-2100, Copenhagen, Denmark

    Arne Schousboe

  4. Brain Research Center, Medical School, University of Tampere, FI-33014, Espoo, Finland

    Pirjo Saransaari

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© 2007 Springer Science+Business Media, LLC

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de Koning, T.J., Fuchs, S.A., Klomp, L.W.J. (2007). 2 Serine, Glycine, and Threonine. In: Lajtha, A., Oja, S.S., Schousboe, A., Saransaari, P. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, New York, NY. https://doi.org/10.1007/978-0-387-30373-4_2

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