Oxidation of γ‐Hydroxybutyrate to Succinic Semialdehyde by a Mitochondrial Pyridine Nucleotide‐Independent Enzyme

: An antibody that inhibits over 95% of the cytosolic NADP+-dependent 7-hydroxybutyrate (GHB) dehydrogenase activity of either rat brain or kidney was found to inhibit only approximately 50% of the conversion of [1–14C]GHB to 14CO2 by rat kidney homogenate. A similar result was obtained with sodium valproate, a potent inhibitor of GHB dehydrogenase. The mitochondrial fraction from rat brain and kidney was found to catalyze the conversion of [1–14C]GHB to 14CO2. The dialyzed mitochondrial fraction also catalyzed the oxidation of GHB to succinic semialdehyde (SSA) in a reaction that did not require added NAD+ or NADPT and which was not inhibited by sodium valproate. The enzyme from the mitochondrial fraction which converts GHB to SSA appears to be distinct from the NADP+-depen-dent cytosolic oxidoreductase which catalyzes this reaction.