High activities of glutamine transaminase K (dichlorovinylcysteine β-Lyase) and ω-amidase in the choroid plexus of rat brain

Arthur J L Cooper, Dicky G. Abraham, Alan S. Gelbard, James C K Lai, Carol Petito

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Certain halogenated hydrocarbons, e.g., dichloroacetylene, are nephrotoxic to experimental animals and neurotoxic to humans; cysteine-S-conjugate β-lyases may play a role in the nephrotoxicity. We now show that with dichlorovinylcysteine as substrate the only detectable cysteine-S-conjugate β-lyase in rat brain homogenates is identical to glutamine transaminase K. The predominant (mitochondrial) form of glutamine transaminase K in rat brain was shown to be immunologically distinct from the predominant (cytosolic) form of the enzyme in rat kidney. Glutamine transaminase K and ω-amidase (constituents of the glutaminase II pathway) activities were shown to be widespread throughout the rat brain. However, the highest specific activities of these enzymes were found in the choroid plexus. The high activity of glutamine transaminase K in choroid plexus was also demonstrated by means of an immunohistochemical staining procedure. Glutamine transaminase K has a broad specificity toward amino acid and α-keto acid substrates. The ω-amidase also has a broad specificity; presumably, however, the natural substrates are α-ketoglutaramate and α-ketosuccinamate, the α-keto acid analogues of glutamine and asparagine, respectively. The high activities of both glutamine transaminase K and ω-amidase in the choroid plexus suggest that the two enzymes are linked metabolically and perhaps are coordinately expressed in that organ. The data suggest that the natural substrate of glutamine transaminase K in rat brain is indeed glutamine and that the metabolism of glutamine through the glutaminase II pathway (i.e., L-glutamine and α-keto acid → α-ketoglutarate and L-amino acid + ammonia) is an important function of the choroid plexus. Moreover, the present findings also suggest that any explanation of the neurotoxicity of halogenated xenobiotics must take into account the role of glutamine transaminase K and its presence in the choroid plexus.

Original languageEnglish
Pages (from-to)1731-1741
Number of pages11
JournalJournal of Neurochemistry
Volume61
Issue number5
StatePublished - Nov 1 1993

Fingerprint

glutamine - phenylpyruvate transaminase
amidase
Lyases
Choroid Plexus
Rats
Brain
glutamine-pyruvate aminotransferase
Glutamine
Keto Acids
Substrates
Cysteine
Enzymes
Halogenated Hydrocarbons
Amino Acids
Asparagine
Xenobiotics
Ammonia
Metabolism

Keywords

  • ω-Amidase
  • Choroid plexus
  • Cysteine-S-conjugate β-lyase
  • Dichlorovinylcysteine
  • Glutamine transaminase K

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Cooper, A. J. L., Abraham, D. G., Gelbard, A. S., Lai, J. C. K., & Petito, C. (1993). High activities of glutamine transaminase K (dichlorovinylcysteine β-Lyase) and ω-amidase in the choroid plexus of rat brain. Journal of Neurochemistry, 61(5), 1731-1741.

High activities of glutamine transaminase K (dichlorovinylcysteine β-Lyase) and ω-amidase in the choroid plexus of rat brain. / Cooper, Arthur J L; Abraham, Dicky G.; Gelbard, Alan S.; Lai, James C K; Petito, Carol.

In: Journal of Neurochemistry, Vol. 61, No. 5, 01.11.1993, p. 1731-1741.

Research output: Contribution to journalArticle

Cooper, AJL, Abraham, DG, Gelbard, AS, Lai, JCK & Petito, C 1993, 'High activities of glutamine transaminase K (dichlorovinylcysteine β-Lyase) and ω-amidase in the choroid plexus of rat brain', Journal of Neurochemistry, vol. 61, no. 5, pp. 1731-1741.
Cooper, Arthur J L ; Abraham, Dicky G. ; Gelbard, Alan S. ; Lai, James C K ; Petito, Carol. / High activities of glutamine transaminase K (dichlorovinylcysteine β-Lyase) and ω-amidase in the choroid plexus of rat brain. In: Journal of Neurochemistry. 1993 ; Vol. 61, No. 5. pp. 1731-1741.
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N2 - Certain halogenated hydrocarbons, e.g., dichloroacetylene, are nephrotoxic to experimental animals and neurotoxic to humans; cysteine-S-conjugate β-lyases may play a role in the nephrotoxicity. We now show that with dichlorovinylcysteine as substrate the only detectable cysteine-S-conjugate β-lyase in rat brain homogenates is identical to glutamine transaminase K. The predominant (mitochondrial) form of glutamine transaminase K in rat brain was shown to be immunologically distinct from the predominant (cytosolic) form of the enzyme in rat kidney. Glutamine transaminase K and ω-amidase (constituents of the glutaminase II pathway) activities were shown to be widespread throughout the rat brain. However, the highest specific activities of these enzymes were found in the choroid plexus. The high activity of glutamine transaminase K in choroid plexus was also demonstrated by means of an immunohistochemical staining procedure. Glutamine transaminase K has a broad specificity toward amino acid and α-keto acid substrates. The ω-amidase also has a broad specificity; presumably, however, the natural substrates are α-ketoglutaramate and α-ketosuccinamate, the α-keto acid analogues of glutamine and asparagine, respectively. The high activities of both glutamine transaminase K and ω-amidase in the choroid plexus suggest that the two enzymes are linked metabolically and perhaps are coordinately expressed in that organ. The data suggest that the natural substrate of glutamine transaminase K in rat brain is indeed glutamine and that the metabolism of glutamine through the glutaminase II pathway (i.e., L-glutamine and α-keto acid → α-ketoglutarate and L-amino acid + ammonia) is an important function of the choroid plexus. Moreover, the present findings also suggest that any explanation of the neurotoxicity of halogenated xenobiotics must take into account the role of glutamine transaminase K and its presence in the choroid plexus.

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