Document Detail


Evidence for the participation of a cytosolic NADP+-dependent oxidoreductase in the catabolism of gamma-hydroxybutyrate in vivo.
MedLine Citation:
PMID:  3106576     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The concentration of gamma-hydroxybutyrate (GHB) in brain, kidney, and muscle as well as the clearance of [1-14C]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 alpha-ketoisocaproate increased GHB levels in kidney and muscle. The half-life of [1-14C]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.
Authors:
E E Kaufman; T Nelson
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of neurochemistry     Volume:  48     ISSN:  0022-3042     ISO Abbreviation:  J. Neurochem.     Publication Date:  1987 Jun 
Date Detail:
Created Date:  1987-06-25     Completed Date:  1987-06-25     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1935-41     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Brain / drug effects*,  metabolism
GABA Antagonists
Glucuronates / metabolism
Hydroxybutyrate Dehydrogenase / antagonists & inhibitors,  metabolism*
Hydroxybutyrates / metabolism*
Keto Acids / pharmacology
Kidney / drug effects,  metabolism
Male
Muscles / drug effects,  metabolism
Phenylacetates / pharmacology
Rats
Rats, Inbred Strains
Sodium Oxybate / metabolism*
Sodium Salicylate / pharmacology
Valproic Acid / pharmacology
gamma-Aminobutyric Acid / analogs & derivatives
Chemical
Reg. No./Substance:
0/GABA Antagonists; 0/Glucuronates; 0/Hydroxybutyrates; 0/Keto Acids; 0/Phenylacetates; 502-85-2/Sodium Oxybate; 54-21-7/Sodium Salicylate; 56-12-2/gamma-Aminobutyric Acid; 692-29-5/succinic semialdehyde; 816-66-0/alpha-ketoisocaproic acid; 99-66-1/Valproic Acid; EC 1.1.1.30/Hydroxybutyrate Dehydrogenase; EC 1.1.1.61/4-hydroxybutyrate dehydrogenase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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