Evidence for a synergistic action of glutaric and 3-hydroxyglutaric acids disturbing rat brain energy metabolism
Gustavo C. Ferreira
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
Search for more papers by this authorAnelise Tonin
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
Search for more papers by this authorPatrícia F. Schuck
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
Search for more papers by this authorCarolina M. Viegas
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
Search for more papers by this authorPaula C. Ceolato
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
Search for more papers by this authorAlexandra Latini
Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil
Search for more papers by this authorMarcos L.S. Perry
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
Search for more papers by this authorAngela T.S. Wyse
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
Search for more papers by this authorCarlos S. Dutra-Filho
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
Search for more papers by this authorClóvis M.D. Wannmacher
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
Search for more papers by this authorCarmen R. Vargas
Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
Serviço de Genética Médica do Hospital de Clínicas de Porto Alegre, RS, Brazil
Search for more papers by this authorCorresponding Author
Moacir Wajner
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
Serviço de Genética Médica do Hospital de Clínicas de Porto Alegre, RS, Brazil
Universidade Luterana do Brasil, Canoas, RS, Brazil
Corresponding author at: Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, Porto Alegre, RS, Brazil. Tel.: +55 51 3308 5571; fax: +55 51 2101 8010.
E-mail address: [email protected] (M. Wajner).
Search for more papers by this authorGustavo C. Ferreira
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
Search for more papers by this authorAnelise Tonin
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
Search for more papers by this authorPatrícia F. Schuck
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
Search for more papers by this authorCarolina M. Viegas
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
Search for more papers by this authorPaula C. Ceolato
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
Search for more papers by this authorAlexandra Latini
Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil
Search for more papers by this authorMarcos L.S. Perry
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
Search for more papers by this authorAngela T.S. Wyse
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
Search for more papers by this authorCarlos S. Dutra-Filho
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
Search for more papers by this authorClóvis M.D. Wannmacher
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
Search for more papers by this authorCarmen R. Vargas
Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
Serviço de Genética Médica do Hospital de Clínicas de Porto Alegre, RS, Brazil
Search for more papers by this authorCorresponding Author
Moacir Wajner
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
Serviço de Genética Médica do Hospital de Clínicas de Porto Alegre, RS, Brazil
Universidade Luterana do Brasil, Canoas, RS, Brazil
Corresponding author at: Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, Porto Alegre, RS, Brazil. Tel.: +55 51 3308 5571; fax: +55 51 2101 8010.
E-mail address: [email protected] (M. Wajner).
Search for more papers by this authorAbstract
Glutaric acidemia type I is an inherited metabolic disorder caused by a severe deficiency of the mitochondrial glutaryl-CoA dehydrogenase activity leading to accumulation of predominantly glutaric and 3-hydroxyglutaric acids in the brain tissue of the affected patients. Considering that a toxic role was recently postulated for quinolinic acid in the neuropathology of glutaric acidemia type I, in the present work we investigated whether the combination of quinolinic acid with glutaric or 3-hydroxyglutaric acids or the mixture of glutaric plus 3-hydroxyglutaric acids could alter brain energy metabolism. The parameters evaluated in cerebral cortex from young rats were glucose utilization, lactate formation and 14CO2 production from labeled glucose and acetate, as well as the activities of pyruvate dehydrogenase and creatine kinase. We first observed that glutaric (5 mM), 3-hydroxyglutaric (1 mM) and quinolinic acids (0.1 μM) per se did not alter these parameters. Similarly, no change of these parameters occurred when combining glutaric with quinolinic acids or 3-hydroxyglutaric with quinolinic acids. In contrast, co-incubation of glutaric plus 3-hydroxyglutaric acids increased glucose utilization, decreased 14CO2 generation from glucose, inhibited pyruvate dehydrogenase activity as well as total and mitochondrial creatine kinase activities. The glutaric plus 3-hydroxyglutaric acids-induced inhibitory effects on creatine kinase were prevented by the antioxidants glutathione and catalase plus superoxide dismutase, indicating the participation of reactive oxygen species. Our data indicate a synergic action of glutaric and 3-hydroxyglutaric acids disturbing energy metabolism in cerebral cortex of young rats.
References
- M.A. Arstall, C. Bailey, W.L. Gross, M. Bak, J.L. Balligand, R.A. Kelly. Reversible S, -nitrosation of creatine kinase by nitric oxide in adult rat ventricular myocytes. J. Mol. Cell. Cardiol. 30: 1998; 979–988
- K.B. Bjugstad, L.S. Crnic, S.I. Goodman, C.R. Freed. Infant mice with glutaric acidaemia type I have increased vulnerability to 3-nitropropionic acid toxicity. J. Inherit. Metab. Dis. 29: 2006; 612–619
10.1007/s10545-006-0102-9 Google Scholar
- K.B. Bjugstad, W.M. Zawada, S. Goodman, C.R. Free. IGF-1 and bFGF reduce glutaric acid and 3-hydroxyglutaric acid toxicity in striatal cultures. J. Inherit. Metab. Dis. 24: 2001; 631–647
- A.M. Das, T. Lucke, K. Ullrich. Glutaric aciduria I: creatine supplementation restores creatine phosphate levels in mixed cortex cells from rat incubated with 3-hydroxyglutarate. Mol. Genet. Metabol. 78: 2003; 108–111
- C.F. de Mello, S. Kölker, B. Ahlemeyer, F.R. de Souza, M.R. Fighera, E. Mayatepek, J. Krieglstein, G.F. Hoffmann, M. Wajner. Intrastriatal administration of 3-hydroxyglutaric acid induces convulsions and striatal lesions in rats. Brain Res. 916: 2001; 70–75
10.1016/S0006-8993(01)02865-7 Google Scholar
- F. de Oliveira Marques, M.E. Hagen, C.D. Pederzolli, A.M. Sgaravatti, K. Durigon, C.G. Testa, C.M. Wannmacher, A.T. de Souza Wyse, M. Wajner, C.S. Dutra-Filho. Glutaric acid induces oxidative stress in brain of young rats. Brain Res. 964: 2003; 153–158
10.1016/S0006-8993(02)04118-5 Google Scholar
- J.C. Dutra, M. Wajner, C.F. Wannmacher, C.S. Dutra-Filho, C.M.D. Wannmacher. Effects of methylmalonate and propionate on glucose and ketone bodies uptake in vitro by brain of developing rats. Biochem. Med. Metab. Biol. 45: 1991; 56–64
- G. da C. Ferreira, C.M. Viegas, P.F. Schuck, A. Latini, C.S. Dutra-Filho, A.T. Wyse, C.M. Wannmacher, C.R. Vargas, M. Wajner. Glutaric acid moderately compromises energy metabolism in rat brain. Int. J. Dev. Neurosci. 23: 2005; 687–693
10.1016/j.ijdevneu.2005.08.003 Google Scholar
- G.C. Ferreira, C.M. Viegas, P.F. Schuck, A. Tonin, C.A. Ribeiro, D. Coelho, M. de, T. Dalla-Costa, A. Latini, A.T. Wyse, C.M. Wannmacher, C.R. Vargas, M. Wajner. Glutaric acid administration impairs energy metabolism in midbrain and skeletal muscle of young rats. Neurochem. Res. 30: 2005; 1123–1131
10.1007/s11064-005-7711-9 Google Scholar
- D. Floret, P. Divry, N. Dingeon, P. Monnet. Glutaric aciduria 1. New case. Arch. Francaises de Pediatrie. 36: 1979; 462–470
- B. Flott-Rahmel, C. Falter, P. Schluff, R. Fingerhut, E. Christensen, C. Jakobs, U. Musshoff, J.D. Fautek, T. Deufel, A. Ludolph, K. Ullrich. Nerve cell lesions caused by 3-hydroxyglutaric acid: a possible mechanism for neurodegeneration in glutaric acidemia I. J. Inherit. Metab. Dis. 20: 1997; 387–390
- A.C. Foster, J.F. Collins, R. Schwarcz. On the excitotoxic properties of quinolinic acid 2,3-piperidine dicarboxylic acids and structurally related compounds. Neuropharmacology. 22: 1983; 1331–1342
- F. Freudenberg, Z. Lukacs, K. Ullrich. 3-Hydroxyglutaric acid fails to affect the viability of primary neuronal rat cells. Neurobiol. Dis. 16: 2004; 581–584
- M.E. Frizzo, C. Schwarzbold, L.O. Porciuncula, K.B. Dalcin, R.B. Rosa, C.A. Ribeiro, D.O. Souza, M. Wajner. 3-Hydroxyglutaric acid enhances glutamate uptake into astrocytes from cerebral cortex of young rats. Neurochem. Int. 44: 2004; 345–353
- C.B. Funk, A.N. Prasad, P. Frosk, S. Sauer, S. Kölker, C.R. Greenberg, M.R. Del Bigio. Neuropathological, biochemical and molecular findings in a glutaric acidemia type 1 cohort. Brain. 128: 2005; 711–722
- S.I. Goodman, M.D. Norenberg, R.H. Shikes, D.J. Breslich, P.G. Moe. Glutaric aciduria: biochemical and morphologic considerations. J. Pediatr. 90: 1977; 746–750
- S.I. Goodman, F.E. Frerman. Organic acidemias due to defects in lysine oxidation: 2-ketoadipic acidemia and glutaric academia. The Metabolic and Molecular Bases of Inherited Disease. 8th ed.. 2001; McGraw-Hill: New York, pp. 2195–2204
- N. Gregersen, N.J. Brandt. Ketotic episodes in glutaryl-CoA dehydrogenase deficiency (glutaric aciduria). Pediatr. Res. 13: 1979; 977–981
- M.P. Heyes, K. Saito, J.S. Crowley, L.E. Davis, M.A. Demitrack, M. Der, L.A. Dilling, J. Elia, M.J. Kruesi, A. Lackner, S.A. Larsen, K. Lee, H.L. Leonard, S.P. Markey, A. Martin, S. Milstein, M.M. Mouradian, M.R. Pranzatelli, B.J. Quearry, A. Salazar, M. Smith, S.E. Strauss, T. Sunderland, S.W. Swedo, W.W. Tourtellotte. Quinolinic acid and kynurenine pathway metabolism in inflammatory and non-inflammatory neurological disease. Brain. 115: 1992; 1249–1273
- G.F. Hoffmann, J. Zschocke. Glutaric aciduria type I: from clinical, biochemical and molecular diversity to successful therapy. J. Inherit. Metab. Dis. 22: 1999; 381–391
- B.P. Hughes. A method for the estimation of serum creatine kinase and its use in comparing creatine kinase and aldolase activity in normal and pathological sera. Clin. Chim. Acta. 7: 1962; 597–603
- S. Kölker, B. Ahlemeyer, R. Huhne, E. Mayatepek, J. Krieglstein, G.F. Hoffmann. Potentiation of 3-hydroxyglutarate neurotoxicity following induction of astrocytic iNOS in neonatal rat hippocampal cultures. Eur. J. Neurosci. 13: 2001; 2115–2122
- S. Kölker, B. Ahlemeyer, J. Krieglstein, G.F. Hoffmann. Contribution of reactive oxygen species to 3-hydroxyglutarate neurotoxicity in primary neuronal cultures from chick embryo telencephalons. Pediatr. Res. 50: 2001; 76–82
- S. Kölker, B. Ahlemeyer, J. Krieglstein, G.F. Hoffmann. 3-Hydroxyglutaric and glutaric acids are neurotoxic through NMDA receptors in vitro. J. Inherit. Metab. Dis. 22: 1999; 259–262
- S. Kulkens, I. Harting, S. Sauer, J. Zschocke, G.F. Hoffmann, S. Gruber, O.A. Bodamer, S. Kölker. Late-onset neurologic disease in glutaryl-CoA dehydrogenase deficiency. Neurology. 64: 2005; 2142–2144
- A. Latini, M. Rodriguez, R. Borba Rosa, K. Scussiato, G. Leipnitz, D. Reis de Assis, G. da Costa Ferreira, C. Funchal, M.C. Jacques-Silva, L. Buzin, R. Giugliani, A. Cassina, R. Radi, M. Wajner. 3-Hydroxyglutaric acid moderately impairs energy metabolism in brain of young rats. Neuroscience. 135: 2005; 111–120
- A. Latini, K. Scussiato, G. Leipnitz, C.S. Dutra-Filho, M. Wajner. Promotion of oxidative stress by 3-hydroxyglutaric acid in rat striatum. J. Inherit. Metab. Dis. 28: 2005; 57–67
10.1007/s10545-005-3677-7 Google Scholar
- A. Latini, R. Borba Rosa, K. Scussiato, S. Llesuy, A. Bello-Klein, M. Wajner. 3-Hydroxyglutaric acid induces oxidative stress and decreases the antioxidant defenses in cerebral cortex of young rats. Brain Res. 956: 2002; 367–373
- B. Leighton, L. Budohoski, F.J. Lozeman, R.A. Challiss, E.A. Newsholme. The effect of prostaglandins E1, E2 and F2 alpha and indomethacin on the sensitivity of glycolysis and glycogen synthesis to insulin in stripped soleus muscles of the rat. Biochem. J. 227: 1985; 337–340
- G. Leipnitz, C. Schumacher, K. Scussiato, K.B. Dalcin, C.M. Wannmacher, A.T. Wyse, C.S. Dutra-Filho, M. Wajner, A. Latini. Quinolinic acid reduces the antioxidant defenses in cerebral cortex of young rats. Int. J. Dev. Neurosci. 23: 2005; 695–701
- T.T. Lima, J. Begnini, J. de Bastiani, D.B. Fialho, A. Jurach, M.C. Ribeiro, M. Wajner, C.F. de Mello. Pharmacological evidence for GABAergic and glutamatergic involvement in the convulsant and behavioral effects of glutaric acid. Brain Res. 802: 1998; 55–60
- O.H. Lowry, N.J. Rosebrough, A.L. Farr, R.J. Randall. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193: 1951; 265–275
- T.M. Lund, E. Christensen, A.S. Kristensen, A. Schousboe, A.M. Lund. On the neurotoxicity of glutaric, 3-hydroxyglutaric, and trans, -glutaconic acids in glutaric acidemia type 1. J. Neurosci. Res. 77: 2004; 143–147
- A. Meister, M.E. Anderson. Glutathione. Annu. Rev. Biochem. 52: 1983; 711–760
- L.O. Porciuncula, T. Emanuelli, R.G. Tavares, C. Schwarzbold, M.E. Frizzo, D.O. Souza, M. Wajner. Glutaric acid stimulates glutamate binding and astrocytic uptake and inhibits vesicular glutamate uptake in forebrain from young rats. Neurochem. Int. 45: 2004; 1075–1086
- O. Ramirez, E. Jiménez. Opposite transitions of chick brain catalytically active cytosolic creatine kinase isoenzymes during development. Int. J. Dev. Neurosci. 18: 2000; 815–823
- A.A. Rasia-Filho, C.A. Fin, M. Alves, M.A. Possa, C. Roehrig, A.M. Feoli, L. Silva, M.L. Perry. Glucose and lactate utilization by the amygdala of male and female rats. Neurochem. Res. 27: 2002; 1583–1588
- D. Reis de Assis, C. Maria Rde, R. Borba Rosa, P.F. Schuck, C.A. Ribeiro, G. da Costa Ferreira, C.S. Dutra-Filho, A. Terezinha de Souza Wyse, C.M. Duval Wannmacher, M.L. Santos Perry, M. Wajner. Inhibition of energy metabolism in cerebral cortex of young rats by the medium-chain fatty acids accumulating in MCAD deficiency. Brain Res. 1030: 2004; 141–151
10.1016/j.brainres.2004.10.010 Google Scholar
- R.B. Rosa, P.F. Schuck, D.R. de Assis, A. Latini, K.B. Dalcin, C.A. Ribeiro, G. da Costa Ferreira, R.C. Maria, G. Leipnitz, M.L. Perry, C.S. Filho, A.T. Wyse, C.M. Wannmacher, M. Wajner. Inhibition of energy metabolism by 2-methylacetoacetate and 2-methyl-3-hydroxybutyrate in cerebral cortex of developing rats. J. Inherit. Metab. Dis. 28: 2005; 501–515
- R.B. Rosa, C. Schwarzbold, K.B. Dalcin, G.C. Ghisleni, C.A. Ribeiro, M.B. Moretto, M.E. Frizzo, G.F. Hoffmann, D.O. Souza, M. Wajner. Evidence that 3-hydroxyglutaric acid interacts with NMDA receptors in synaptic plasma membranes from cerebral cortex of young rats. Neurochem. Int. 45: 2004; 1087–1094
- A. Santamaria, M.E. Jimenez-Capdeville, A. Camacho, E. Rodriguez-Martinez, A. Flores, S. Galvan-Arzate. In vivo hydroxyl radical formation after quinolinic acid infusion into rat corpus striatum. Neuroreport. 12: 2001; 2693–2696
- A. Santamaria, C. Rios. MK-801, an N, -methyl-d, -aspartate receptor antagonist, blocks quinolinic acid-induced lipid peroxidation in rat corpus striatum. Neurosci. Lett. 159: 1993; 51–54
- S.W. Sauer, J.G. Okun, M.A. Schwab, L.R. Crnic, G.F. Hoffmann, S.I. Goodman, D.M. Koeller, S. Kölker. Bioenergetics in glutaryl-coenzyme A dehydrogenase deficiency: a role for glutaryl-coenzyme A. J. Biol. Chem. 280: 2005; 21830–21836
- P.F. Schuck, A. Tonin, G. da Costa Ferreira, R.B. Rosa, A. Latini, F. Balestro, M.L. Perry, C.M. Wannmacher, A.T. de Souza Wyse, M. Wajner. In vitro effect of quinolinic acid on energy metabolism in brain of young rats. Neurosci. Res. 57: 2007; 277–288
- P.F. Schuck, A. Tonin, G. da Costa Ferreira, C.M. Viegas, A. Latini, C.M. Duval Wannmacher, A.T. de Souza Wyse, C.S. Dutra-Filho, M. Wajner. Kynurenines impair energy metabolism in rat cerebral cortex. Cell. Mol. Neurobiol. 27: 2007; 147–160
- P.F. Schuck, G. Leipnitz, C.A. Ribeiro, K.B. Dalcin, D.R. Assis, A.G. Barschak, V. Pulrolnik, C.M. Wannmacher, A.T. Wyse, M. Wajner. Inhibition of creatine kinase activity in vitro by ethylmalonic acid in cerebral cortex of young rats. Neurochem. Res. 27: 2002; 1633–1639
- R. Schwarcz, A.C. Foster, E.D. French, W.O. Whetsell Jr., C. Kohler. Excitotoxic models for neurodegenerative disorders. Life Sci. 35: 1984; 19–32
- R. Schwarcz, R. Pellicciari. Manipulation of brain kynurenines: glial targets, neuronal effects, and clinical opportunities. J. Pharmacol. Exp. Therapeut. 303: 2002; 1–10
- I.D. Schweigert, C. Roehrig, F. da Costa, F. Scheibel, C.J. Gottfried, L.N. Rotta, C.A. Goncalves, D.O. Souza, M.L. Perry. High extracellular K+ levels stimulate acetate oxidation in brain slices from well and malnourished rats. Neurochem. Res. 29: 2004; 1547–1551
- A.M. Sgaravatti, R.B. Rosa, P.F. Schuck, C.A. Ribeiro, C.M. Wannmacher, A.T. Wyse, C.S. Dutra-Filho, M. Wajner. Inhibition of brain energy metabolism by the alpha-keto acids accumulating in maple syrup urine disease. Biochim. Biophys. Acta. 1639: 2003; 232–238
- N. Shimojo, K. Naka, C. Nakajima, C. Yoshikawa, K. Okuda, K. Okada. Test-strip method for measuring lactate in whole blood. Clin. Chem. 35: 1989; 1992–1994
- C.G. Silva, A.R. Silva, C. Ruschel, C. Helegda, A.T. Wyse, C.M. Wannmacher, C.S. Dutra-Filho, M. Wajner. Inhibition of energy production in vitro by glutaric acid in cerebral cortex of young rats. Metab. Brain Dis. 15: 2000; 123–131
- O. Stachowiak, M. Dolder, T. Wallimann, C. Richter. Mitochondrial creatine kinase is a prime target of peroxynitrite-induced modification and inactivation. J. Biol. Chem. 273: 1998; 16694–16699
- T.W. Stone. Neuropharmacology of quinolinic and kynurenic acids. Pharmacol. Rev. 45: 1993; 309–379
- K.A. Strauss, D.H. Morton. Type I glutaric aciduria. Part 2. A model of acute striatal necrosis. Am. J. Med. Genet., Part C: Semin. Med. Genet. 121: 2003; 53–70
- M. Toyomizu, S. Yamahira, Y. Shimomura, Y. Akiba. Metabolic acidosis inhibits pyruvate oxidation in chick liver by decreasing activity of pyruvate dehydrogenase complex. Life Sci. 65: 1999; 37–43
- P.A. Trinder. Determination of blood glucose using on oxidase system with a non-carcinogenic chromogen. J. Clin. Pathol. 22: 1969; 158–161
- K. Ullrich, B. Flott-Rahmel, P. Schluff, U. Musshoff, A. Das, T. Lucke, R. Steinfeld, E. Christensen, C. Jakobs, A. Ludolph, A. Neu, R. Roper. Glutaric aciduria type I: pathomechanisms of neurodegeneration. J. Inherit. Metab. Dis. 22: 1999; 392–403
- S. Varadkar, R. Surtees. Glutaric aciduria type I and kynurenine pathway metabolites: a modified hypothesis. J. Inherit. Metab. Dis. 27: 2004; 835–842
- M. Wajner, S. Kölker, D.O. Souza, G.F. Hoffmann, C.F. de Mello. Modulation of glutamatergic and GABAergic neurotransmission in glutaryl-CoA dehydrogenase deficiency. J. Inherit. Metab. Dis. 27: 2004; 825–828
- T. Wallimann, M. Dolder, U. Schlattner, M. Eder, T. Hornemann, T. Kraft, M. Stolz. Creatine kinase: an enzyme with a central role in cellular energy metabolism. Magn. Reson. Mater. Phys. Biol. Med. 6: 1998; 116–119
- H. Wolosker, R. Panizzutti, S. Engelender. Inhibition of creatine kinase by S, -nitrosoglutathione. FEBS Lett. 392: 1996; 274–276
