Abstract
Mitochondria and nuclei of various tissues, including brain and liver, are capable of producingγ-aminobutyrate (GABA) fromL-glutamate, but poorly, if at all, fromD-glutamate. The amino nitrogen of glutamate is found in the reaction product. The enzymes responsible for GABA formation were solubilized from crude liver cell nuclei by Triton X-100. The reaction is NAD+ dependent Oxygen, FMN, Mg2+, and pyridoxalphosphate enhanced GABA formation. NADP+, coenzyme A, ornithine, 2-oxoglutarate, and aminooxyacetic acid, among others, inhibited the formation of GABA. On the basis of the available information the reaction sequence, is formulated tentatively as follows:
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Seiler, N., Knodgen, B., andAskar, A. 1973. The formation ofγ-aminobutyrate in liver cell nuclei. Hoppe-Seyler's Z. Physiol. Chem. 354:467–470.
Benohr, H.C., Franz, W., andKrisch, K. 1966. Carboxylesterasen der Mikrosomenfraktion. Hydrolyse von Tributyrin Procain, und Phenocetin durch einige Organe und Lebermikrosomen verschiedener Tierarten. Naunyn-Schmiedebergs Arch. Pharmakol. Exp. Pathol. 255:163–177.
Blobel, G., andPotter, Van R. 1966. Nuclei from rat liver: Isolation method that combines purity with high yield Science 154:1662–1665.
Kato, T., andKurokawa, M. 1967. Isolation of cell nuclei from the mammalian cerebral cortex and their assortment on a morphological basis. J. Cell Biol. 32:649–662.
Umbreit, W.W., Burris, R.H., andStauffer, J.P. (eds.). 1964. Manometric Techniques, 4th ed., Burgess Publishing Co., Minneapolis, Minnesota.
Seiler, N. 1970. Use of the dansyl reaction in biochemical analysis. Methods Biochem. Anal. 18:259–337.
Seiler, N., andWiechmann, M. 1969. Zum Vorkommen derγ-Amino-buttersaure und derγ-Amino-β-hydroxybuttersaure in Tierischem Gewebe. Hoppe-Seyler's Z. Physiol. Chem. 350:1493–1500.
Seiler, N., andWiechmann, M. 1968. Die Bestimmung derγ-Amino buttersaure in 10−11-Mol-Bereich als I-Dimethylamino-naphthalin-5-sulfonyl-Derivat. Hoppe-Seyler's Z. Physiol. Chem. 349:588–594.
Seiler, N., andKnodgen, B. 1973. Quantitative mass spectrometry by internal standardization using a single focussing mass spectrometer and the peak switching facilities of a peak matching device. Org. Mass Spectrom. 7:97–105.
Bachelard, H.S. 1965. Glucose metabolism and α-keto-acids in rat brain and liver in vivo. Nature 205:905–904.
Fischer, F.G., andBohn, H. 1957. Uber die Bestimmung von Spermin, Spermidin und anderen biogenen Aminen nach papierelektrophoretischer Abtrennung und ihre Mengenverhaltnisse in tierischen Organen. Hoppe-Seylers Z. Physiol. Chem. 308:108–115.
Chiari, D., andRohr, M. 1967. Dunnschichtchramatographische Trennung von Ketocarbonsauren auf Zelluloseschichten. Microchim. Acta 1:140–142.
Ley, H., Roberts, E., andBaxter, C. 1966. Pages 490–504,in Lang, K., Lehnartz, E., Hoffman-Ostenhof, O., andSiebert, G. (eds.), Handbuch der Physiologischen und Pathologisch-Chemischen Analyse, Vol. 6B, Springer, Heidelberg and New York.
Singer, T.P., Bernath, P., andLusty, C.J. 1970. Pages 1573–1578,in Bergmeyer, H.U. (e.), Methoden der enzymatischen Analyse, Vol. 2, Verlag-Chemie, Weinheim.
Hartree, E.F. 1972. Determination of protein. A modification of the Lowry method that gives a linear photometric response. Anal. Biochem. 48:422–427.
Fleck, A., andMunro, H.N. 1962. The precision of ultraviolet absorption measurements in the Schmidt-Thannhauser procedure for nucleic acid estimation. Biochim. Biophys. Acta 55:571–583.
Munro, H.N., andFleck, A. 1966. Recent developments in the measurement of nucleic acids in biological materials. Analyst (London) 91:78–88.
Croft, D.N., andLubran, M. 1965. The estimation of deoxyribonucleic acid in the presence of sialic acid: Application to analysis of human gastric washings. Biochem. J. 95:612–620.
Wagner, G. 1975. Ph. D. thesis, University of Frankfurt, Germany.
Roberts, E., andSimonsen, D.G. 1963. Some properties ofL-glutamic acid decarboxylase in mouse brain. Biochem. Pharmacol. 12: 113–134.
Salganicoff, L., andDe Robertis, E. 1963. Subcellular distribution of glutamic decarboxylase and gamma aminobutyric alpha-ketoglutaric transaminase. Life Sci. 2:85–91.
Balazs, R., Dahl, D., andHarwood, J.R. 1966. Subcellular distribution of enzymes of glutamate metabolism in rat brain. J. Neurochem. 13:897–905.
Haber, B., Kuriyama, K., andRoberts, E. 1970. An anion stimulatedL-glutamic acid decarboxylase in non-neural tissues: Occurrence and subcellular localization in mouse kidney and developing chick embryo brain. Biochem. Pharmacol. 19:1119–1136.
Haber, B., Kuriyama, K., andRoberts, E. 1970. Mitochondrial localization of a newL-glutamic acid decarboxylase in mouse and human brain. Brain Res. 22:105–112.
Lovtrup, S. 1961. The subcellular localization of glutamic decarboxylase in rat brain. J. Neurochem. 8:243–245.
Kuriyama, K., Haber, B., andRoberts, E. 1970. Occurrence of a newL-glutamic acid decarboxylase in several blood vessels of the rabbit. Brain Res. 23:121–123.
Drummond, R.J., andPhillips, A.T. 1974.L-Glutamic acid, decarboxylase in non-neural tissues of the mouse. J. Neurochem. 23:1207–1213.
MacDonnell, P., andGreengard, O. 1975. The distribution of glutamate decarboxylase in rat tissues; isotopic versus fluorimetric assays. J. Neurochem. 24:615–618.
Seiler, N., andAl-Therib, M.J. 1974. Putrescine catabolism in mammalian brain Biochem. J. 144:29–35.
Seiler, N., andEichentopf, B. 1975. 4-Aminobutyrate in mammalian putrescine catabolism. Biochem. J. 152:201–210.
Seiler, N., andKnodgen, B. 1971. Die Umwandlung von Glutamisaure, Putrescin und Ornithin in dieγ-Aminobuttersaure in Gehrin. Hoppe-Seyler's Z. Physiol. Chem. 352:97–105.
Seiler, N., Wiechmann, M., Fischer, H.A., andWerner, G. 1971. The incorporation of putrescine carbon intoγ-aminobutyric acid in rat liver and brain in vivo. Brain Res. 28:317–325.
Seiler, N., Al-Therib, M.J., andKataoka, K. 1973. Formation of GABA from putrescine in the brain of fish (Salmo irideus Gibb). J. Neurochem. 20:699–708.
Whelan, D.T., Scriver, C.R. andMohyuddin, F. 1969. Glutamic acid decarboxylase and gamma-aminobutyric acid in mammalian kidney. Nature 224:916–917.
Lancaster, G., Mohyuddin, F., Scriver, C.R., andWhelan, D.T. 1973. Aγ-aminobutyrate pathway in mammalian kidney cortex. Biochim. Biophys. Acta 297:229–240.
Gonnard, P., andWicker, A. 1974. Apropos de la glutamate décarboxylase mitochondriale cérébrale. Biochimie 56:1437–1438.
Miller, L. P., andMartin, D.L. 1973. Artifact in glutamate decarboxylase assay. Life Sci. 13:1023–1032.
Wu, J.-Y., andRoberts, E. 1974. Properties of brainL-glutamate decarboxylase. Inhibition studies. J. Neurochem. 23:759–767.
Di Prisco, G., Banay-Schwartz, M., andStrecker, H.J. 1968. Glutamate dehydrogenase in nuclear and mitochondrial fractions of rat liver. Biochem. Biophys. Res. Commun. 33:606–612.
Herzfeld, A. 1972. The distribution of glutamate dehydrogenase in rat tissue. Enzyme 13:246–251.
Herzfeld, A., Federmann, M., andGreengard, O. 1973. Subcellular morphometric and biochemical analyses of developing rat hepatocytes. J. Cell Biol. 57:475–483.
Frieden, C. 1959. Glutamic dehydrogenase III. The order of substrate addition in the enzymatic reaction. J. Biol. Chem. 234:2891–2896.
Olson, J.A., andAnfinsen, C.B. 1959. Kinetic and equilibrium studies on crystallineL-glutamic acid dehydrogenase. J. Biol. Chem. 202:841–856.
McKhann, G.M., andTower, D.B. 1959. Gamma-aminobutyric acid: A substance for oxidative metabolism in the cerebral cortex. Am. J. Physiol. 196:36–38.
Sacktor, B., andPacker, L. 1962. Reactions of the respiratory chain in brain mitochondrial preparations. J. Neurochem. 9:371–382.
Tsukada, Y., Nagata, Y., andTakagaki, G. 1957. Metabolism ofγ-aminobutyric acid in brain slices. Proc. Jpn. Acad. 33:510–514.
Bacila, M., Campello, A.P., Vianna, C.H.M., andVoss, D.O. 1964. The respiratory chain of rat cerebrum and cerebellum mitochondria: Respiration and oxidative phosphorylation. J. Neurochem. 11:231–242.
Balazs, R., Biesold, D., andMagyar, K. 1963. Some properties of rat brain mitochondrial preparations: Respiratory control. J. Neurochem. 10:685–708.
Buniatian, H.C., Movcessian, C.G., andUrgandjian, M.G. 1964. The effect ofγ-aminobutyric acid on oxidative phosphorylation of brain mitochondria., Pages 15–26,in Buniatian, H.C. (ed.), Problems in Brain Biochemistry, Academy of Science, Armenian SSR.
Roberts, E., andFrankel, S. 1951. Glutamic acid decarboxylase in brain. J. Biol. Chem. 188:789–795.
Weinstein, H., Roberts, E., andKakefuda, T. 1963. Studies of subcellular distribution ofγ-aminobutyric acid and glutamic acid decarboxylase in mouse brain. Biochem. Pharmacol. 12:503–509.
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Seiler, N., Wagner, G. NAD+-dependent formation ofγ-aminobutyrate (GABA) from glutamate. Neurochem Res 1, 113–131 (1976). https://doi.org/10.1007/BF00965636
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DOI: https://doi.org/10.1007/BF00965636