Hostname: page-component-84b7d79bbc-g7rbq Total loading time: 0 Render date: 2024-07-31T21:19:07.576Z Has data issue: false hasContentIssue false
  • English
  • Français

Hypothesis: A Role for Quinolinic Acid in the Neuropathology of Glutaric Aciduria Type I

Published online by Cambridge University Press:  05 January 2016

Melvyn P. Heyes
Melvyn P. Heyes*
Affiliation:
Laboratory of Neurophysiology. National Institute of Mental Health, Bethesda, Maryland
*
NIH Animal Center, National Institute of Mental Health, Laboratory of Neurophysiology, Building 112, Room 205, P.O. Box 289, Poolesville, M.D., U.S.A. 20837
Rights & Permissions [Opens in a new window]

Abstract:

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Glutaric aciduria type I is an autosomal recessive metabolic disorder of children associated with severe dystonic motor disturbances and degeneration in the cerebral cortex, striatum and cerebellum. Biochemical studies demonstrate a deficiency in the enzyme glutaryl-CoA dehydrogenase. This enzyme metabolizes substrate derived from dietary tryptophan that could otherwise be converted to quinolinic acid within the brain. The law of mass action predicts that the production of quinolinic acid should be increased in glutaric aciduria type I. Quinolinic acid is a potent neurotoxin and convulsant when it is injected into the central nervous system of experimental animals. This paper argues that quinolinic acid may accumulate within the brain and cause the neuropathology of glutaric aciduria type I.

Type
Research Article
Information
Canadian Journal of Neurological Sciences , Volume 14 , Issue S3 , August 1987 , pp. 441 - 443
Copyright
Copyright © Canadian Neurological Sciences Federation 1987

References

REFERENCES

1.Hagberg, B, Kyllerman, M, Steen, G.Dyskinesia and dystonia in neurometabolic disorders. Neuropediatrie 1979; 10: 305–320.CrossRefGoogle ScholarPubMed
2.Gregersen, N.The acyl-CoA dehydrogenation deficiencies. Blackwell Scientific Publications, Oslo, 1985.Google ScholarPubMed
3.Goodman, SI. Markey, SP, Moe, PG, et al. Glutaric aciduria; a “new” disorder of amino acid metabolism. Biochem Medicine 1975; 12: 12–21.CrossRefGoogle ScholarPubMed
4.Goodman, SI, Kohloff, JG. Glutaric aciduria: inherited deficiency of glutaryl-CoA dehydrogenase activity. Biochem Medicine 1975: 13: 138–140.CrossRefGoogle ScholarPubMed
5.Gregersen, N, Brandt, NJ, Christensen, E, et al. Glutaric aciduria: clinical and laboratory findings in two brothers. J Pediatrics 1977; 90: 740–745.CrossRefGoogle ScholarPubMed
6.Brandt, NJ, Brandt, S, Christensen, E, et al. Glutaric aciduria in progressive choreo-athetosis. Clinical Genetics 1978: 13: 77–80.CrossRefGoogle ScholarPubMed
7.Kyllerman, M., Steen, G.Intermittently progressive dyskinetic syndrome in glutaric aciduria. Neuropediatrie 1977; 8: 397–404.CrossRefGoogle ScholarPubMed
8.Whelan, DT. Hill, R, Ryan, ED, Spate, M.Glutaric acidemia: Investigation of a patient and his family. Pediatrics 1979; 63: 88.CrossRefGoogle ScholarPubMed
9.Floret, D, Divry, P, Dingeon, N, et al. Aciduria glutarique. Arch franc Pediat 1979; 36: 462–470.Google Scholar
10.Goodman, SI, Norenberg, MD, Shikes, RH, et al. Glutaric aciduria: biochemical and morphologic considerations. J Pediatrics 1977; 90: 746–750.CrossRefGoogle ScholarPubMed
11.Christensen, E, Brandt, NJ. Studies on glutaryl-CoA dehydroge-nase in leucocytes, fibroblasts and amniotic fluid cells. The normal enzyme and the mutant form in patients with glutaric aciduria. Clinica Chimica Acta 1978; 88: 267–276.CrossRefGoogle Scholar
12.Christensen, E.Improved assay of glutaryl-CoA dehydrogenase in cultured cells and liver: application to glutaric aciduria type 1. Clinica Chimica Acta 1983; 129: 91–97.CrossRefGoogle Scholar
13.Hankes, LV, Brown, RR, Lippincott, S, et al. Effects of L-trypto-phan-2-l4C in man. J Lab and Clinical Med 1967; 69: 313–324.Google ScholarPubMed
14.Bender, DA. Biochemistry of tryptophan in health and disease. Molec Aspects of Med 1982:6: 101–197.CrossRefGoogle Scholar
15.Schwarcz, R, Whetsell, WO, Mangano, RM. Quinolinic acid: an endogenous metabolite that produces axon-sparing lesions in rat brain. Science 1983; 219: 316–318.CrossRefGoogle ScholarPubMed
16.Wolfensberger, M, Amsler, U.Cuenod, M, et al. Identification of quinolinic acid in rat and human brain tissue. Neurosci Letts 1983; 41: 247–252.CrossRefGoogle ScholarPubMed
17.McGeer, EG, Singh, E.Neurotoxic effects of endogenous materials: quinolinic acid, L-pyroglutamic acid and TRH. Exp Neurol 1984; 86: 410–413.CrossRefGoogle ScholarPubMed
18.Stone, TW, Connick, JH. Quinolinic acid and other kynurenines in the central nervous system. Neuroscience 1985: 15: 597–617.CrossRefGoogle ScholarPubMed
19.Nasu, S, Yamaguchi, K, Sakakibara, S, et al. The effect of pyrazines on the metabolism of tryptophan and nicotinamide adenine dinu-cleotide in the rat. Biophysica Acta 1981: 677: 109–119.Google Scholar
20.Foster, A, Miller, LP, Oldendorf, WH, et al. Studies on the disposition of quinolinic acid after intracerebral or systemic administration in the rat. Expl Neurol 1984; 84: 428–440.CrossRefGoogle ScholarPubMed
21.Gal, EM, Sherman, AD. L-kynurenine, its synthesis and possible regulatory function in brain. Neurochem Res 1980; 5: 223–239.CrossRefGoogle ScholarPubMed
22.Moroni, F, Lombardi, G, Carla, V, et al. The excitotoxin quinolinic acid is present and unevenly distributed in the rat brain. Brain Res 1984; 295: 352–355.CrossRefGoogle ScholarPubMed
23.Brandt, NJ, Gregersen, N.Christensen, E, et al. Treatment of glutaryl-CoA dehydrogenase deficiency (glutaric aciduria). J Pediatrics 1979, 94: 669–673.CrossRefGoogle ScholarPubMed
24.Moroni, F, Lombardi, G, Carla, V.Changes of the brain content of quinolinic acid: possible correlation with brain pathology. Soc Neurosci Abstr 1985; 241.1, p. 821.Google Scholar
25.Parli, CJ, Krieter, P, Schmidt, B.Metabolism of 6-Chlorotryptophan to 4-chloro-3-hydroxyanthranilic acid: a potent inhibitor of 3-hydroxyanthranilic acid oxidase. Achv Biochem and Biophy 1980; 203: 161–166.CrossRefGoogle ScholarPubMed
26.Cook, JS, Pogson, CI. Tryptophan and glucose metabolism in rat liver cells. Biochem J 1983: 214: 511–516.CrossRefGoogle ScholarPubMed
27.Foster, AC, Vezzani, A, French, ED. et al. Kynurenic acid blocks neurotoxicity and seizures induced in rats by the related brain metabolite quinolinic acid. Neurosci Lett 1984: 48: 273–278.CrossRefGoogle ScholarPubMed