Evidence for a role of high Km aldehyde reductase in the degradation of endogenous gamma-hydroxybutyrate from rat brain.
gamma-Hydroxybutyrate (GHB) is a putative neurotransmitter in brain. We have already demonstrated that it is transformed into gamma-aminobutyrate (GABA) by rat brain slices incubated under physiological conditions. This conversion occurs via a GABA-transaminase reaction. Therefore, succinic semialdehyde, the oxidative derivative of GHB, appears to be the primary catabolite of GHB degradation. Apparently, the kinetic characteristics and pH optimum of GHB dehydrogenase (high Km aldehyde reductase) in vitro do not favor a role for this enzyme in endogenous brain GHB oxidation. However, in the presence of glucuronate, glutamate, NADP and pyridoxal phosphate, pure GHB dehydrogenase, coupled to purified GABA-transaminase does produce GABA from GHB at an optimum pH close to the physiological value and with a low Km for GHB.
D000612:4-Aminobutyrate Transaminase / Q000378:metabolism; D000429:Alcohol Oxidoreductases / Q000378:metabolism*; D000818:Animals; D001923:Brain Chemistry; D006863:Hydrogen-Ion Concentration; D006884:Hydroxybutyrate Dehydrogenase / Q000378:metabolism*; D006885:Hydroxybutyrates / Q000378:metabolism*; D007700:Kinetics; D010084:Oxidation-Reduction; D051381:Rats; D012978:Sodium Oxybate / Q000378:metabolism*; D013379:Substrate Specificity; D005680:gamma-Aminobutyric Acid / Q000096:biosynthesis
D006885:Hydroxybutyrates; D005680:gamma-Aminobutyric Acid; D012978:Sodium Oxybate; D000429:Alcohol Oxidoreductases; C019642:alcohol dehydrogenase (NADP+); D006884:Hydroxybutyrate Dehydrogenase; C019416:4-hydroxybutyrate dehydrogenase; D000612:4-Aminobutyrate Transaminase