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Evidence for the Participation of a Cytosolic NADP + ‐Dependent Oxidoreductase in the Catabolism of γ‐Hydroxybutyrate In Vivo
Author(s) -
Kaufman Elaine E.,
Nelson Thomas
Publication year - 1987
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1987.tb05758.x
Subject(s) - catabolism , dehydrogenase , enzyme , oxidoreductase , biochemistry , chemistry , in vivo , metabolism , cytosol , kidney , biology , endocrinology , microbiology and biotechnology
The concentration of γ‐hydroxybutyrate (GHB) in brain, kidney, and muscle as well as the clearance of [1‐ 14 C]GHB in plasma have been found to be altered by the administration of a number of metabolic intermediates and drugs that inhibit the NADP + ‐dependent oxidoreductase, “GHB dehydrogenase,” an enzyme that catalyzes the oxidation of GHB to succinic semialdehyde. Administration of valproate, salicylate, and phenylacetate, all inhibitors of GHB dehydrogenase, significantly increased the concentration of GHB in brain; salicylate increased GHB concentration in kidney, and α‐ketoisocaproate increased GHB levels in kidney and muscle. The half‐life of [1‐ 14 C]GHB in plasma was decreased by D‐glucuronate, a compound that stimulates the oxidation of GHB by this enzyme and was increased by a competitive substrate of the enzyme, L‐gulonate. The results of these experiments suggest a role for GHB dehydrogenase in the regulation of tissue levels of endogenous GHB.