Kaufman E E, Nelson T
J Neurochem. 1987 Jun;48(6):1935-41. doi: 10.1111/j.1471-4159.1987.tb05758.x.
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.
已发现，给予多种代谢中间体和抑制烟酰胺腺嘌呤二核苷酸磷酸（NADP⁺）依赖性氧化还原酶“γ-羟基丁酸脱氢酶”的药物后，大脑、肾脏和肌肉中γ-羟基丁酸（GHB）的浓度以及血浆中[1-¹⁴C]GHB的清除率会发生改变。γ-羟基丁酸脱氢酶是一种催化GHB氧化为琥珀酸半醛的酶。给予丙戊酸盐、水杨酸盐和苯乙酸盐（均为γ-羟基丁酸脱氢酶的抑制剂）后，大脑中GHB的浓度显著升高；水杨酸盐使肾脏中GHB浓度升高，α-酮异己酸盐使肾脏和肌肉中GHB水平升高。血浆中[1-¹⁴C]GHB的半衰期因D-葡萄糖醛酸而缩短，D-葡萄糖醛酸是一种能刺激该酶氧化GHB的化合物，而该酶的竞争性底物L-古洛糖酸则使其半衰期延长。这些实验结果表明，γ-羟基丁酸脱氢酶在内源性GHB的组织水平调节中发挥作用。
