Skip to main content
SpringerLink
Log in

7 Sulfur-Containing Amino Acids

  • Reference work entry
  • First Online:
Handbook of Neurochemistry and Molecular Neurobiology

Abstract:

This chapter reviews the structure, synthesis and biological activity of acidic sulfur-containing amino acids (SAAs) that have neuroexcitatory properties. These include the endogenous SAAs L-cysteine, L-cysteine sulfinic acid, L-cysteic acid, L-homocysteine, L-homocysteine sulfinic acid and L-homocysteic acid as well as the exogenous excitants L-serine-O-sulfate and S-sulfo-L-cysteine.

The endogenous SAAs are synthesised in situ in the brain and are derived from either L-methionine (L-homocysteine) or L-cysteine (L-cysteic acid and L-cystine sulphinate). The biosynthetic pathway leading to L-homocysteic and L-homocysteine sulfinic acids has not been identified. L-cysteine and its oxidised counterpart, L-cystine, are rate-limiting precursors for glutathione (GSH) synthesis via the γ-glutamyl cycle.

One or more subtypes of glutamate receptor mediate the neuroexcitatory activity of SAAs. However, evidence is emerging which suggests that the function of SAAs in the brain is centered more on astrocytes than is the case for ‘classical’ neurotransmitters such as glutamate. Transport of SAAs, as well as de novo synthesis of both SAAs and GSH, is primarily localized to astrocytes. The demonstration of L-glutamate-stimulated release of L-homocysteic acid from astrocytes is further evidence that their activity is largely glial-based.

Several of the SAAs are cytotoxic, acting either as glutamate-like toxins or as gliotoxins. An alternative mechanism of L-cysteine toxicity may be caused by the chemical reactivity of the sulfydryl group, leading to formation of hydrogen peroxide. None of the SAAs have been directly linked to neurodegenerative disease, but it is possible that certain SAAs (for example, L-homocysteine) may exacerbate glutamate-mediated toxicity in some brain pathologies.

There is still much to be discovered regarding the biological role of the SAAs, particularly as regards understanding neuronal-glial interactions and the importance of astrocytes in promoting neuronal survival. It is anticipated that further insights into this important class of neuroactive substance will emerge, leading to a better appreciation of the role of SAAs in excitatory neurotransmission.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 299.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

l-cys:

l-cysteine

l-cySS:

l-cystine

l-CSA:

l-cysteine sulfinic acid

l-CA:

l-cysteic acid

l-Hcys:

l-homocysteine

l-HcySS:

l-homocystine

l-HCSA:

l-homocysteine sulfinic acid

l-HCA:

l-homocysteic acid

l-SOS:

l-serine-O-sulfate

l-SSC:

S-sulfo-l-cysteine

GSH:

glutathione

SAA:

sulfur-containing amino acid

NMDA:

N-methyl-d-aspartate

d-APV:

d-2-amino-5-phosphonopentanoic acid

MPEP:

2-methyl-6-(phenylethynyl)pyridine

ASC:

alanine serine cysteine

xc − :

l-cySS–glutamate exchanger

PI:

phosphatidylinositol bisphosphate

References

  • Allen JW, Shanker G, Aschner M. 2001. Methylmercury inhibits the in vitro uptake of the glutathione precursor, cystine, in astrocytes, but not in neurons. Brain Res 894: 131–140.

    Article  CAS  PubMed  Google Scholar 

  • Almarghini K, Remy A, Tappaz M. 1991. Immunocytochemistry of the taurine biosynthesis enzyme, cysteine sulfinate decarboxylase, in the cerebellum: Evidence for a glial localisation. Neuroscience 43: 111–119.

    Article  CAS  PubMed  Google Scholar 

  • Anderson KJ, Monaghan DT, Bridges RJ, Tavoularis AL, Cotman CW. 1990. Autoradiographic characterization of putative excitatory amino acid transport sites. Neuroscience 38: 311–322.

    Article  CAS  PubMed  Google Scholar 

  • Anderson MF, Nilsson M, Sims NR. 2004. Glutathione monoethylester prevents mitochondrial glutathione depletion during focal cerebral ischaemia. Neurochem Int 44: 153–159.

    Article  CAS  PubMed  Google Scholar 

  • Badaloo A, Reid M, Forrester T, Heird WC, Jahoor F. 2002. Cysteine supplementation improves the erythrocyte glutathione synthesis rate in children with severe edematous malnutrition. Am J Clin Nutr 76: 646–652.

    Article  CAS  PubMed  Google Scholar 

  • Baker DA, Shen H, Kalivas PW. 2002a. Cystine/glutamate exchange serves as the source for extracellular glutamate: Modifications by repeated cocaine administration. Amino Acids 23: 161–162.

    Article  CAS  PubMed  Google Scholar 

  • Baker DA, Xi ZX, Shen H, Swanson CJ, Kalivas PW. 2002b. The origin and neuronal function of in vivo nonsynaptic glutamate. J Neurosci 22: 9134–9441.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bannai S. 1984. Induction of cystine and glutamate transport activity in human fibroblasts by diethylmaleate and other electrophilic agents. J Biol Chem 259: 2435–2440.

    Article  CAS  PubMed  Google Scholar 

  • Bannai S, Christensen HN, Vadgama JV, Ellory JC, Engelsberg E, et al. 1984. Amino acid transport systems. Nature 311: 308.

    CAS  PubMed  Google Scholar 

  • Bannai S, Kitamura E. 1980. Transport interaction of l-cystine and l-glutamate in human dipliod fibroblasts in culture. J Biol Chem 255: 2372–2376.

    Article  CAS  PubMed  Google Scholar 

  • Bannai S, Kitamura E. 1981. Role of proton dissociation in the transport of cystine and glutamate in human diploid fibroblasts in culture. J Biol Chem 256: 5770–5772.

    Article  CAS  PubMed  Google Scholar 

  • Bender AS, Reichelt W, Norenberg MD. 2000. Characterization of cystine uptake in cultured astrocytes. Neurochem Int 37: 269–276.

    Article  CAS  PubMed  Google Scholar 

  • Benz B, Grima G, Do KQ. 2004. Glutamate-induced homocysteic acid release from astrocytes: Possible implication in glia-neuron signalling. Neuroscience 124: 377–386.

    Article  CAS  PubMed  Google Scholar 

  • Bouvier M, Miller BA, Szatkowski M, Attwell D. 1991. Electrogenic uptake of sulphur-containing analogues of glutamate and aspartate by Muller cells from the salamander retina. J Physiol 444: 441–457.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brand A, Leibfritz D, Hamprecht B, Dringen R. 1998. Metabolism of cysteine in astroglial cells: Synthesis of hypotaurine and taurine. J Neurochem 71: 827–832.

    Article  CAS  PubMed  Google Scholar 

  • Brennan L, Hewage C, Malthouse JPG, McBean GJ. 2003. An NMR study of alterations in [1-13C]glucose metabolism in C6 glioma cells by gliotoxic amino acids. Neurochem Int 42: 441–448.

    Article  CAS  PubMed  Google Scholar 

  • Brennan L, Hewage C, Malthouse JPG, McBean GJ. 2004. Gliotoxins disrupt alanine metabolism and glutathione production in C6 glioma cells: a 13C NMR spectroscopic study. Neurochem Int 45: 1155–1165.

    Article  CAS  PubMed  Google Scholar 

  • Bridges CC, Kekuda R, Wang H, Prasad PD, Mehta P, et al. 2001. Structure, function, and regulation of human cystine/glutamate transporter in retinal pigment epithelial cells. Invest Ophthalmol Vis Sci 42: 47–54.

    CAS  PubMed  Google Scholar 

  • Bridges RJ, Hatalski CG, Shim SN, Cummings BJ, Vijayan V, et al. 1992. Gliotoxic actions of excitatory amino acids. Neuropharmacology 31: 899–907.

    Article  CAS  PubMed  Google Scholar 

  • Bridges RJ, Kesslak JP, Nieto SM, Broderick JT, Yu J, et al. 1987b. A l-[3H]glutamate binding site on glia: An autoradiographic study on implanted astrocytes. Brain Res 415: 163–168.

    Article  CAS  PubMed  Google Scholar 

  • Bridges RJ, Koh J, Hatalski CG, Cotman CW. 1991. Increased excitotoxic vulnerability of cortical cultures with reduced levels of glutathione. Eur J Pharmacol 192: 199–200.

    Article  CAS  PubMed  Google Scholar 

  • Bridges RJ, Nieto SM, Kadri M, Cotman CW. 1987a. A novel chloride-dependent l-[3H]glutamate binding site in astrocyte membranes. J Neurochem 48: 1–7.

    Article  Google Scholar 

  • Broer A, Brookes N, Ganapathy V, Dimmer KS, Wagner CA, et al. 1999. The astroglial ASCT2 amino acid transporter as a mediator of glutamine efflux. J Neurochem 73: 2184–2194.

    CAS  PubMed  Google Scholar 

  • Butcher SP, Cameron D, Kendall L, Griffiths R. 1992. Homocysteine-induced alterations in extracellular amino acids in rat hippocampus. Neurochem Int 20: 75–80.

    Article  CAS  PubMed  Google Scholar 

  • Chen Q, Harris C, Brown CS, Howe A, Surmeier DJ, et al. 1995. Glutamate-mediated excitotoxic death of cultured striatal neurones is mediated by non-NMDA receptors. Exp Neurol 136: 212–224.

    Article  CAS  PubMed  Google Scholar 

  • Chen Y, Swanson RA. 2003. The glutamate transporters EAAT2 and EAAT3 mediate cysteine uptake in cortical neuronal cultures. J Neurochem 84: 1332–1339.

    Article  CAS  PubMed  Google Scholar 

  • Cho Y, Bannai S. 1990. Uptake of glutamate and cystine in C-6 glioma cells and in cultured astrocytes. J Neurochem 55: 2091–2097.

    Article  CAS  PubMed  Google Scholar 

  • Clarke R, Smith AD, Jobst KA, Refsum H, Sutton L, et al. 1998. Folate, vitamin B12 and serum total homocysteine levels in confirmed Alzheimer's disease. Arch Neurol 55: 1449–1455.

    Article  CAS  PubMed  Google Scholar 

  • Coppen A, Bolander-Gouaille C. 2005. Treatment of depression: time to consider folic acid and Vitamin B12. J Psychopharmacol 19: 59–65.

    Article  CAS  PubMed  Google Scholar 

  • Croucher MJ, Thomas LS, Ahmadi H, Lawrence V, Harris JR. 2001. Endogenous sulphur-containing amino acids: Potent agonists at presynaptic metabotropic glutamate autoreceptors in the rat central nervous system. Br J Pharmacol 133: 815–814.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cuénod M, Do KQ, Grandes P, Morino P, Streit P. 1990. Localisation and release of homocysteic acid, an excitatory sulfur-containing amino acid. J Histochem Cytochem 38: 1713–1715.

    Article  PubMed  Google Scholar 

  • Cuénod M, Grandes P, Zangerle P, Streit P, Do KQ. 1993. Sulphur-containing excitatory amino acids in intercellular communication. Biochem Soc Transact 21: 72–77.

    Article  Google Scholar 

  • Curras MC, Dingledine R. 1992. Selectivity of amino acid transmitters acting at N-methyl-d-aspartate and amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors. Mol Pharmacol 41: 520–526.

    CAS  PubMed  Google Scholar 

  • Curtis DR, Watkins JC. 1960. The excitation and depression of spinal neurones by structurally related amino acids. J Neurochem 6: 117–141.

    Article  CAS  PubMed  Google Scholar 

  • Danbolt NC. 2001. Glutamate uptake. Prog Neurobiol 65: 1–105.

    Article  CAS  PubMed  Google Scholar 

  • Do KQ, Mattenberger M, Streit P, Cuénod M. 1986. In vitro release of endogenous excitatory sulfur-containing amino acids from various rat brain regions. J Neurochem 46: 779–786.

    Article  CAS  PubMed  Google Scholar 

  • Do KQ, Tappaz ML. 1996. Specificity of cysteine sulphinate decarboxylase (CSD) for sulphur-containing amino acids. Neurochem Int 28: 363–371.

    Article  CAS  PubMed  Google Scholar 

  • Dowd LA, Coyle AJ, Rothstein JD, Pritchett DB, Robinson MB. 1996. Comparison of Na+-dependent glutamate transport activity in synaptosomes, C6 glioma, and Xenopus oocytes expressing excitatory amino acid carrier 1 (EAAC1). Mol Pharmacol 49: 465–473.

    CAS  PubMed  Google Scholar 

  • Dringen R. 2000. Metabolism and functions of glutathione in brain. Prog Neurobiol 62: 649–671.

    Article  CAS  PubMed  Google Scholar 

  • Dringen R, Hirrlinger J. 2003. Glutathione pathways in the brain. Biol Chem 384: 505–516.

    Article  CAS  PubMed  Google Scholar 

  • Dringen R, Pfeiffer B, Hamprecht B. 1999. Synthesis of the antioxidant glutathione in neurons: Supply by astrocytes of CysGly as precursor for neuronal glutathione. J Neurosci 19: 562–569.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dunlop J, Grieve A, Damgaard I, Schousboe A, Griffiths R. 1992. Sulphur-containing excitatory amino acid-evoked Ca2+-independent release of d-[3H]aspartate from cultured cerebellar granule cells: The role of glutamate receptor activation coupled to reversal of the acidic amino acid plasma membrane carrier. Neuroscience 50: 107–115.

    Article  CAS  PubMed  Google Scholar 

  • Dunlop J, Grieve A, Schousboe A, Griffiths R. 1991. Stimulation of gamma-[3H]aminobutyric acid release from cultured mouse cerebral cortex neurons by sulphur-containing excitatory amino acid transmitter candidates: Receptor activation mediates two distinct mechanisms of release. J Neurochem 57: 1388–1397.

    Article  CAS  PubMed  Google Scholar 

  • Flynn J, McBean GJ. 2000. Kinetic and pharmacological analysis of l-[35S]cystine transport into rat brain synaptosomes. Neurochem Int 36: 513–521.

    Article  CAS  PubMed  Google Scholar 

  • Frandsen A, Schousboe A, Griffiths R. 1993. Cytotoxic actions and effects on intracellular Ca2+ and cGMP concentrations of sulphur-containing excitatory amino acids in cultured cerebrocortical neurons. J Neurosci Res 34: 331–339.

    Article  CAS  PubMed  Google Scholar 

  • Gazit V, Ben-Abraham R, Coleman R, Weizman A, Katz Y. 2004. Cysteine-induced hypoglycaemic brain damage: An alternative mechanism to excitotoxicity. Amino Acids 26: 163–168.

    Article  CAS  PubMed  Google Scholar 

  • Gochenauer GE, Robinson MB. 2001. Dibutyryl-cAMP (dbcAMP) up-regulates astrocytic chloride-dependent l-[3H]glutamate transport and expression of both system xc(-) subunits. J Neurochem 78: 276–286.

    Article  CAS  PubMed  Google Scholar 

  • Grandes P, Do KQ, Morino P, Cuénod M, Streit P. 1991. Homocysteate, an excitatory transmitter candidate localised in glia. Eur J Neurosci 3: 1370–1373.

    Article  PubMed  Google Scholar 

  • Grange E, Gharib A, Lepetit P, Guillaud J, Sarda N, et al. 1992. Brain protein sythesis in the conscious rat using l-[35S]methionine: relationship of methioine specific activity between plasma and precursor compartment and evaluation of methionine metabolic pathways. J Neurochem 59: 1437–1443.

    Article  CAS  PubMed  Google Scholar 

  • Grieve A, Griffiths R. 1992. Simultaneous measurement by HPLC of the excitatory amino acid candidates homocysteate and homocysteine sulphinate supports a predominantly astrocytic localisation. Neurosci Lett 28: 1–5.

    Article  Google Scholar 

  • Griffiths R. 1990. Cysteine sulphinate (CSA) as an excitatory amino acid transmitter candidate in the mammalian central nervous system. Prog Neurobiol 35: 313–323.

    Article  CAS  PubMed  Google Scholar 

  • Griffiths R. 1993. The biochemistry and pharmacology of sulphur-containing amino acids. Biochem Soc Transact 21: 63–72.

    Article  Google Scholar 

  • Guebel D, Torres NV. 2004. Dynamics of sulfur amino acids in mammalian brain: Assessment of the astrocytic-neuronal cysteine interaction by a mathematical hybrid model. Biochim Biophys Acta 1647: 12–28.

    Article  CAS  Google Scholar 

  • Hayes D, Wießner M, Rauen T, McBean GJ. 2005. Transport of l-[14C]cystine and l-[14C]cysteine by subtypes of high affinity glutamate transporters over-expressed in HEK cells. Neurochem Int 46: 585–594.

    Article  CAS  PubMed  Google Scholar 

  • Ho PI, Collins SC, Dhitavat S, Ortiz D, Ashline D, et al. 2001. Homocysteine potentiates beta-amyloid neurotoxicity: Role of oxidative stress. J Neurochem 78: 249–253.

    Article  CAS  PubMed  Google Scholar 

  • Ho PI, Ashline D, Dhitavat S, Ortiz D, Collins SC, et al. 2003. Folate deprivation induces neurodegeneration: Roles of oxidative stress and increased homocysteine. Neurobiol Dis 14: 32–42.

    Article  CAS  PubMed  Google Scholar 

  • Ho PI, Ortiz D, Rogers E, Shea TB. 2002. Multiple aspects of homocysteine neurotoxicity: Glutamate excitotoxicity, kinase hyperactivation and DNA damage. J Neurosci Res 70: 694–702.

    Article  CAS  PubMed  Google Scholar 

  • Huang G, Dragan M, Freeman D, Wilson JX. 2005. Activation of catechol-O-methyltransferase in astrocytes stimulates homocysteine synthesis and export to neurons. Glia 51: 47-55.

    Google Scholar 

  • Ida S, Ohkuma S, Kimori M, Kuriyama K, Morimoto N, et al. 1985. Regulatory role of cysteine dioxygenase in cerebral biosynthesis of taurine. Analysis using cerebellum from 3-acetylpyridine-treated rats. Brain Res 344: 62–69.

    Article  CAS  PubMed  Google Scholar 

  • James SJ, Slikker WJ, Melnyk S, New E, Pogribna M, et al. 2005. Thimerosal neruotoxicity is associated with glutathione depletion: Protection with glutathione precursors. Neurotoxicology 26: 1–8.

    Article  CAS  PubMed  Google Scholar 

  • Janaky R, Varga V, Hermann A, Saransaari P, Oja SS. 2000. Mechanisms of l-cysteine neurotoxicity. Neurochem Res 25: 1397–1405.

    Article  CAS  PubMed  Google Scholar 

  • Jaro-Prado A, Ortega-Vazquez A, Martinez-Ruano L, Rios C, Santamaria A. 2003. Homocysteine-induced brain lipid peroxidation: Effects of NMDA receptor blockade, antioxidant treatment and nitric oxide synthase inhibition. Neurotox Res 5: 237–243.

    Article  Google Scholar 

  • Johnson CL, Johnson CG. 1993. Substance P regulation of glutamate and cystine transport in human astrocytoma cells. Recept Channels 1: 53–59.

    CAS  PubMed  Google Scholar 

  • Kanai Y. 1997. Family of neutral and acidic amino acid transporters: Molecular biology, physiology and medical implications. Curr Opin Cell Biol 9: 565–572.

    Article  CAS  PubMed  Google Scholar 

  • Kanai Y, Hediger MA. 2003. The glutamate and neutral amino acid transporter family: Physiological and pharmacological implications. Eur J Pharmacol 479: 234–247.

    Article  CAS  Google Scholar 

  • Kato S, Negishi K, Mawatari K, Kuo CH. 1992. A mechanism of glutamate toxicity in C6 glioma cells involving inhibition of cystine uptake leading to glutathione depletion. Neuroscience 48: 903–914.

    Article  CAS  PubMed  Google Scholar 

  • Keller HJ, Do Q, Kollinger M, Winterhalter HK, Cuénod M. 1989. Cysteine: Depolarisation-induced release from rat brain in vitro. J Neurochem 52: 1801–1806.

    Article  CAS  PubMed  Google Scholar 

  • Kilpatrick IC, Mozley LS. 1986. An initial analysis of the regional distribution of excitatory sulphur-containing amino acids in the rat brain. Neurosci Lett 72: 189–193.

    Article  CAS  PubMed  Google Scholar 

  • Kingston AE, Lowndes J, Evans N, Clark B, Tomlinson R, et al. 1998. Sulphur-containing amino acids are agonists for group 1 metabotropic receptors expressed in clonal RGT cell lines. Neuropharmacology 37: 277–287.

    Article  CAS  PubMed  Google Scholar 

  • Klancnik JM, Cuénod M, Gähwiler BH, Jiang ZP, Do KQ. 1992. Release of endogenous amino acids, including homocysteic and cysteine sulphinic acid from rat hippocampal slices evoked by electrical stimulation of Schaffer collateral-commisural fibres. Neuroscience 49: 557–570.

    Article  CAS  PubMed  Google Scholar 

  • Knickelbein RG, Seres T, Lam G, Johnston RB, Warshaw JB. 1997. Characterisation of multiple cysteine and cystine transporters in rat alveolar type II cells. Am J Physiol 273: L1147–L1153.

    CAS  PubMed  Google Scholar 

  • Kocki T, Luchowski P, Luchowska E, Wielosz M, Turski WA, et al. 2003. l-Cysteine sulphinate, endogenous sulphur-containing amino acid, inhibits rat brain kynurenic acid production via selective interference with kynurenine aminotransferaseII. Neurosci Lett 346: 97–100.

    Article  CAS  PubMed  Google Scholar 

  • Koyama Y, Ishibashi T, Baba A. 1995. Increase in chloride-dependent l-glutamate transport activity in synaptic membrane after in vivo ischaemic treatment. J Neurochem 65: 1798–1804.

    Article  CAS  PubMed  Google Scholar 

  • Koyama Y, Kimura Y, Hashimoto H, Matsuda T, Baba A. 2000. l-lactate inhibits l-cystine/l-glutamate exchange transport and decreases glutathione content in rat cultured astrocytes. J Neurosci Res 59: 685–691.

    Article  CAS  PubMed  Google Scholar 

  • Kranich O, Dringen R, Sandberg M, Hamprecht B. 1998. Utilization of cystine and cysteine precursors for the synthesis of glutathione in astroglial cultures: Preference for cystine. Glia 22: 11–18.

    Article  CAS  PubMed  Google Scholar 

  • Kranich O, Hamprecht B, Dringen R. 1996. Different preferences in the utilisation of amino acids for glutathione synthesis in cultured neurons and astroglial cells derived from rat brain. Neurosci Lett 219: 211–214.

    Article  CAS  PubMed  Google Scholar 

  • Kruman I, Culmsee C, Chan SL, Kruman Y, Gou Z, et al. 2000. Homocysteine elicits a DNA damage response in neurons that promotes apoptosis and hypersensitivity to excitotoxicity. J Neurosci 20: 6920–6926.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li H, Marshall ZM, Whorton AR. 1999a. Stimulation of cystine uptake by nitric oxide: Regulation of endothelial cell glutathione levels. Am J Physiol 276: C803–C811.

    Article  CAS  PubMed  Google Scholar 

  • Li X, Wallin C, Weber SG, Sandberg M. 1999b. Net efflux of cysteine, glutathione and related metabolites from rat hippocampal slices during oxygen/glucose deprivation: Dependence on γ-glutamyl transpeptidase. Brain Res 815: 81–88.

    Article  CAS  PubMed  Google Scholar 

  • Lipton SA, Kim WK, Choi YB, Kumar S, D'Emilia DM, et al. 1997. Neurotoxicity associated with dual actions of homocysteine at the N-methyl-d-aspartate receptor. Proc Natl Acad Sci USA 94: 5923–5928.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Loscalzo J. 2002. Homocysteine and dementias. New Engl J Med 346: 466–468.

    Article  PubMed  Google Scholar 

  • Maler JM, Seifert W, Hüther G, Wiltfang J, Rüther E, et al. 2003. Homocysteine induces cell death of rat astrocytes in vitro. Neurosci Lett 347: 85–88.

    Article  CAS  PubMed  Google Scholar 

  • Mattson MP, Shea TB. 2003. Folate and homocysteine metabolism in neural plasticity and neurodegenerative disorders. Trends Neurosci 26: 137–146.

    Article  CAS  PubMed  Google Scholar 

  • McBean GJ. 2002. Cerebral cystine uptake: a tale of two transporters. Trends Pharmacol Sci 23: 299–302.

    Article  CAS  PubMed  Google Scholar 

  • McBean GJ, Flynn J. 2001. Molecular mechanisms of cystine transport. Biochem Soc Transact 29: 717–722.

    Article  CAS  Google Scholar 

  • Miralles VJ, Martínez-López I, Zaragozá R, Borrás E, García C, et al. 2001. Na+ dependent glutamate transporters (EAAT1, EAAT2 and EAAT3) in primary astrocyte cultures: Effects of oxidative stress. Brain Res 922: 21–29.

    Article  CAS  PubMed  Google Scholar 

  • Moran MM, Melendez R, Baker D, Kalivas PW, Seamans JK. 2003. Cystine/glutamate antiporter regulation of vesicular glutamate release. Ann N Y Acad Sci 1003: 445–447.

    Article  PubMed  Google Scholar 

  • Murphy TH, Baraban JM. 1990. Glutamate toxicity in immature cortical neurones preceeds development of glutamate receptor currents. Brain Res Dev Brain Res 57: 146–150.

    Article  CAS  PubMed  Google Scholar 

  • Murphy TH, Miyamoto M, Sastre A, Schnaar RL, Coyle JT. 1989. Glutamate toxicity in a neuronal cell line involves cystine transport leading to oxidative stress. Neuron 2: 1547–1558.

    Article  CAS  PubMed  Google Scholar 

  • Murphy TH, Schnaar RL, Coyle JT. 1990. Immature cortical neurones are uniquely sensitive to glutamate toxicity by inhibition of cystine uptake. FASEB J 4: 1624–1633.

    Article  CAS  PubMed  Google Scholar 

  • Nath KA, Salahudeen AK. 1993. Autooxidation of cysteine generates hydrogen peroxide: Cytotoxicity and attenuation of pyruvate. Am J Physiol 264: F306–F314.

    CAS  PubMed  Google Scholar 

  • O'Connor E, Devesa A, Garcia C, Puertes IR, Pellin A, et al. 1995. Biosynthesis and maintenance of GSH in primary astrocyte cultures: Role of cysteine and ascorbate. Brain Res 680: 157–163.

    Article  CAS  PubMed  Google Scholar 

  • Oja SS, Janáky R, Varga V, Saransaari P. 2000. Modulation of glutamate receptor functions by glutathione. Neurochem Int 37: 299–306.

    Article  CAS  PubMed  Google Scholar 

  • Outinen PA, Sood SK, Liaw PC, Sarge KD, Maeda N, et al. 1998. Characterization of the stress-inducing effects of homocysteine. Biochem J 332: 213–221.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pancetti F, Oyarcee M, Aranda M, Parodi J, Aguayo LG, et al. 2004. S-methylcysteine may be a causative factor in monohalomethane neurotoxicity. Neurotoxicology 25: 817–823.

    Article  CAS  PubMed  Google Scholar 

  • Parpura V, Basarsky TA, Liu F, Jeftinija K, Jeftinija S, et al. 1994. Glutamate-mediated astrocyte-neuron signalling. Nature 369: 744–747.

    Article  CAS  PubMed  Google Scholar 

  • Parsons RB, Waring RH, Ramsden DB, Williams AC. 1998. In vitro effect of the cysteine metabolites homocysteic acid, homocysteine and cysteic acid upon human neuronal cell lines. Neurotoxicology 19: 599–603.

    CAS  PubMed  Google Scholar 

  • Patel SA, Warren BA, Rhoderick JF, Bridges RJ. 2004. Differentiation of substrate and non-substrate inhibitors of transport system : An obligate exchanger of l-glutamate and l-cystine. Neuropharmacology 46: 273–284.

    Article  CAS  PubMed  Google Scholar 

  • Pellerin L, Magistretti PJ. 1994. Glutamate uptake into astrocytes stimulates aerobic glycolysis: A mechanism coupling neuronal activity to glucose utilisation. Proc Natl Acad Sci USA 91: 10623–10629.

    Article  Google Scholar 

  • Peng L, Swanson RA, Hertz L. 2001. Effects of l-glutamate, d-aspartate and monesin on glycolytic and oxidative glucose metabolism in mouse astrocyte cultures: Further exidence that glutamate uptake is metabolically driven by oxidative metabolism. Neurochem Int 38: 437–443.

    Article  CAS  PubMed  Google Scholar 

  • Porter RH, Roberts PJ. 1993. Glutamate metabotropic receptor activation in neonatal rat cerebral cortex by sulphur-containing excitatory amino acids. Neurosci Lett 154: 78–80.

    Article  CAS  PubMed  Google Scholar 

  • Pow DV. 2001a. Visualising the activity of the cystine-glutamate antiporter in glial cells using antibodies to aminoadipic acid, a selectively transported substrate. Glia 34: 27–38.

    Article  CAS  PubMed  Google Scholar 

  • Pow DV. 2001b. Amino acids and their transporters in the retina. Neurochem Int 38: 463–484.

    Article  CAS  PubMed  Google Scholar 

  • Pullan LM, Olney JW, Price MT, Compton RP, Hood WF, et al. 1987. Excitatory amino acid receptor potency and subclass specificity of sulfur-containing amino acids. J Neurochem 49: 1301–1307.

    Article  CAS  PubMed  Google Scholar 

  • Reichelt W, Stabel-Burow J, Pannicke T, Weichert H, Heinemann U. 1997. The glutathione level of retinal Müller glial cells is dependent on the high-affinity sodium-dependent uptake of glutamate. Neuroscience 77: 1213–1224.

    Article  CAS  PubMed  Google Scholar 

  • Robinson MB. 2002. Regulated trafficking of neurotransmitter transporters: Common notes but different melodies. J Neurochem 80: 1–11.

    Article  CAS  PubMed  Google Scholar 

  • Robinson MB, Sinor JD, Dowd LA, Kerwin JF. 1993. Subtypes of sodium-dependent high affinity l-[3H]glutamate transport activity: Pharmacologic specificity and regulation by sodium and potassium. J Neurochem 60: 167–179.

    Article  CAS  PubMed  Google Scholar 

  • Rothstein JD, Dykes-Hoberg M, Pardo CA, Bristol LA, Kuncl RW, et al. 1996. Knockout of glutamate transporters reveals a major role for astroglial transport in excitotoxicity and clearance of glutamate. Neuron 16: 675–686.

    Article  CAS  PubMed  Google Scholar 

  • Rothstein JD, Martin L, Levey AI, Dykes-Hoberg M, Jin L, et al. 1994. Localisation of neuronal and glial glutamate transporters. Neuron 13: 635–643.

    Article  Google Scholar 

  • Sagara JI, Miura K, Bannai S. 1993a. Cystine uptake and glutathione level in foetal brain cells in primary culture and in suspension. J Neurochem 61: 1667–1671.

    Article  CAS  PubMed  Google Scholar 

  • Sagara JI, Miura K, Bannai S. 1993b. Maintenance of neuronal glutathione by glial cells. J Neurochem 61: 1672–1676.

    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 

  • Sato H, Tamba M, Ishii T, Bannai S. 1999. Cloning and expression of a plasma membrane cystine/glutamate exchange transporter composed of two distinct proteins. J Biol Chem 274: 11455–11458.

    Article  CAS  PubMed  Google Scholar 

  • Sato H, Tamba M, Kuriyama-Matsumura K, Okuno S, Bannai S. 2000. Molecular cloning and expression of human xCT, the light chain of amino acid transport system xc. Antioxid Redox Signal 2: 665–671.

    Article  CAS  PubMed  Google Scholar 

  • Schurr A, West CA, Heine MF, Rigor BM. 1993. The neurotoxicity of sulfur-containing amino acids in energy-deprived rat hippocampal slices. Brain Res 601: 317–320.

    Article  CAS  PubMed  Google Scholar 

  • Selema G, Cristofol RM, Gasso S, Griffiths R, Rodriguez-Farre E. 1997. Sulphur-containing amino acids modulate noradrenaline release from hippocampal slices. J Neurochem 68: 1534–1541.

    Article  CAS  PubMed  Google Scholar 

  • Shanker G, Allen JW, Mutkus LA, Aschner M. 2001. Methylmercury inhibits cysteine uptake in cultured primary astrocytes, but not in neurons. Brain Res 914: 159–165.

    Article  CAS  PubMed  Google Scholar 

  • Shanker G, Aschner M. 2001. Identification and characterisation of uptake systems for cystine and cysteine in cultured astrocytes and neurones: Evidence for methylmercury-targeted disruption of astrocyte transport. J Neurosci Res 66: 998–1002.

    Article  CAS  PubMed  Google Scholar 

  • Shih AY, Murphy TH. 2001. xCt cystine transporter expression in HEK293 cells: Pharmacology and localization. Biochem Biophys Res Commun 282: 1132–1137.

    Article  CAS  PubMed  Google Scholar 

  • Stone TW. 2000. Development and therapeutic potential of kynurenic acid and kynurenine derivatives for neuroprotection. Trends Pharmacol Sci 21: 149–154.

    Article  CAS  PubMed  Google Scholar 

  • Sugiyama H, Ito I, Hirono C. 1987. A new type of glutamate receptor linked to inositol phosphate metabolism. Nature 325: 531–533.

    Article  CAS  PubMed  Google Scholar 

  • Tang XC, Kalivas PW. 2003. Bidirectional modulation of cystine/glutamate exchanger activity in cultured cortical astrocytes. Ann N Y Acad Sci 1003: 472–475.

    Article  PubMed  Google Scholar 

  • Thompson GA, Kilpatrick IC. 1996. The neurotransmitter candidature of sulphur-containing excitatory amino acids in the mammalian central nervous system. Pharmacol Ther 72: 25–36.

    Article  CAS  PubMed  Google Scholar 

  • Tsai MJ, Chang YF, Schwarcz R, Brookes N. 1996. Characterisation of l-α-aminoadipic acid transport in cultured rat astrocytes. Brain Res 741: 166–173.

    Article  CAS  PubMed  Google Scholar 

  • Tschopp P, Streit P, Do KQ. 1992. Homocysteate and homocysteine sulfinate, excitatory transmitter candidates present in rat astroglial cultures. Neurosci Lett 145: 6–9.

    Article  CAS  PubMed  Google Scholar 

  • Vandenberg RJ, Mitrovic AD, Johnston GAR. 1998. Serine-O-sulphate transport by the human glutamate transporter, EAAT2. Br J Pharmacol 123: 1593–1600.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vollenweider FX, Cuénod M, Do KQ. 1990. Effect of climbing fibre deprivation on release of endogenous aspartate, glutamate and homocysteate in slices of rat cerebellar hemispheres and vermis. J Neurochem 54: 1533–1540.

    Article  CAS  PubMed  Google Scholar 

  • Wang XF, Cynader MS. 2000. Astrocytes provide cysteine to neurons by releasing glutathione. J Neurochem 74: 1434–1442.

    Article  CAS  PubMed  Google Scholar 

  • Warr O, Takahashi M, Attwell D. 1999. Modulation of extracellular glutamate concentration in rat brain slices by cystine-glutamate exchange. J Physiol 514: 783–793.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Warren BA, Patel JR, Nunn PB, Bridges RJ. 2004. The lathryus excitotoxin beta-N-oxalyl-l-alpha, beta-diaminopropinic acid is a substrate of the l-cystine/l-glutamate exchanger system xc-. Toxicol Appl Pharmacol 154: 83–92.

    Article  CAS  Google Scholar 

  • White AR, Huang X, Jobling MF, Barrow CJ, Beyreuther K, et al. 2001. Homocysteine potentiates copper- and amyloid beta peptide-mediated toxicity in primary neuronal cultures: possible risk factors in the Alzheimer's-type neurodegenerative pathways. J Neurochem 76: 1509–1520.

    Article  CAS  PubMed  Google Scholar 

  • Wu JY, Moss LG, Chen MS. 1979. Tissue and regional distribution of cysteic acid decarboxylase. A new assay method. Neurochem Res 4: 201–212.

    Article  CAS  PubMed  Google Scholar 

  • Ye ZC, Rothstein JD, Sontheimer H. 1999. Compromised glutamate transport in human glioma cells: Reduction-mislocalization of sodium-dependent glutamate transporters and enhanced activity of cystine-glutamate exchange. J Neurosci 19: 10767–10777.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zerangue H, Kavanaugh MP. 1996a. Flux coupling in a neuronal glutamate transporter. Nature 383: 634–637.

    Article  CAS  PubMed  Google Scholar 

  • Zerangue N, Kavanaugh MP. 1996b. Interaction of l-cysteine with a human excitatory amino acid transporter. J Physiol 493: 419–423.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Authors
  1. G. J. McBean
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  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

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Springer Science+Business Media, LLC

About this entry

Cite this entry

McBean, G.J. (2007). 7 Sulfur-Containing Amino Acids. 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_7

Download citation

Publish with us

Policies and ethics

Search

Navigation