Evidence for a role of high Km aldehyde reductase in the degradation of endogenous γ‐hydroxybutyrate from rat brain

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Abstract
γ‐Hydroxybutyrate (GHB) is a putative neurotransmitter in brain. We have already demonstrated that it is transformed into γ‐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 K m, 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 K m for GHB.