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Neurochemical Research

, Volume 16, Issue 9, pp 965–974 | Cite as

An overview of γ-hydroxybutyrate catabolism: The role of the cytosolic NADP+-dependent oxidoreductase EC 1.1.1.19 and of a mitochondrial hydroxyacid-oxoacid transhydrogenase in the initial, rate-limiting step in this pathway

  • Elaine E. Kaufman
  • Thomas Nelson
Original Articles

Summary

Two enzymes have been found which catalyze the initial step in the catabolism of GHB. The oxidation of GHB to SSA, catalyzed by both of these enzymes, is coupled to the reduction of an oxoacid. In the case of the mitochondrial transhydrogenase, the coupling is obligatory. Although coupling is not obligatory for the GHB dehydrogenase, the stimulation provided by the coupled reaction, and the nature of the kinetics of the uncoupled reaction, may not only allow the reaction to proceed, but may provide a means of regulating the rate of the reaction under in vivo conditions. Since the oxidation of GHB to SSA is the rate limiting step in the overall catabolic pathway (the rate of conversion of GHB to SSA proceeds at approximately one one thousandth of the rate at which SSA is oxidized to succinate by SSA dehydrogenase (30)), factors which regulate the rate of either or both of these enzymes will, in turn, influence tissue levels of endogenous GHB as well as the duration and magnitude of the physiological effect of a dose of GHB.

Keywords

Succinate Initial Step Physiological Effect NADP Couple Reaction 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations used in this paper

GHB

γ-hydroxybutyrate

SSA

succinic semialdehyde

DTT

dithiothreitol

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Copyright information

© Plenum Publishing Corporation 1991

Authors and Affiliations

  • Elaine E. Kaufman
    • 1
  • Thomas Nelson
    • 1
  1. 1.Department of Health and Human ServicesLaboratory of Cerebral Metabolism, National Institute of Mental Health, United States Public Health ServiceBethesda

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