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

FEBS Letters

Bourguignon, Jean-Jacques²  Vayer, Philippe¹  Mandel, Paul¹  Schmitt, Martine²  Maitre, Michel¹ 

[1] Centre de Neurochimie du CNRS and Unité 44 INSERM 5 rue Blaise Pascal, 67084 Strasbourg Cedex, France;Laboratoire de Pharmacochimie Moléculaire (ERA 393 du CNRS), 5 rue Blaise Pascal, 67084 Strasbourg Cedex, France

关键词: γ-Hydroxybutyrate;    Catabolism;    Rat brain;    GABA-T;    4-aminobutyrate-2-oxoglutarate aminotransferase (EC 2.6.1.19);    GHB;    γ-hydroxybutyrate;    GABA;    γ-aminobutyrate;    AET;    aminoethyl-isothiouronium bromide;    hydrobromide;    SSA;    succinic semialdehyde;   

DOI  :  10.1016/0014-5793(85)80426-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown