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Post-mortem changes implicate adenine nucleotides and pyridoxal-5′-phosphate in regulation of brain glutamate decarboxylase

Naturevolume 266pages847848 (1977) | Download Citation

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Abstract

GLUTAMATE decarboxylase (GAD) is the enzyme responsible for the synthesis of γ-aminobutyric acid (GABA), an important neurotransmitter in the CNS (ref. 1). Alterations in GAD activity have been implicated in epilepsy, druginduced convulsions and neurological diseases such as Huntington's chorea and parkinsonism2–5. Although this enzyme has been under study for over 20 yr, little is known of the molecular mechanisms by which its activity is regulated. Recent results suggest that the degree of saturation of GAD by its cofactor, pyridoxal-5′-phosphate (pyridoxal-P), in vivo could be determined by a balance between the rate of dissociation of the cofactor from the enzyme brought about by glutamate and the rate of association of the cofactor with the apoenzyme, which is inhibited strongly by the nucleotides ATP and ADP (ref. 6). Thus, it seemed likely that degree of saturation of GAD by pyridoxal-P in vivo might be low and might increase as a consequence of post-mortem changes in the levels of ATP and ADP. Additional activation in vitro during preparative steps might also occur because nucleotide levels would be reduced during homogenisation. Data presented here confirm these expectations and implicate the adenine nucleotides and pyridoxal-P in the regulation of GABA synthesis.

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Affiliations

  1. Experimental Therapeutics Branch, National Institute of Neurological and Communicative Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, 20014

    • L. P. MILLER
    •  & J. R. WALTERS
  2. Department of Chemistry, University of Maryland, College Park, Maryland, 20742

    • D. L. MARTIN

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https://doi.org/10.1038/266847a0

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