Formation of γ‐Amino‐β‐Hydroxybutyric Acid from 2‐Hydroxyputrescine in Rat Brain

Abstract

gamma-Amino-beta-[3H]hydroxybutyric acid ([3H]-GABOB) was formed in rat brain from 2-[3H]-hydroxyputrescine that had been chemically synthesized from 2-oxoputrescine and [3H]sodium borohydride. After the injection of 2-[3H]hydroxyputrescine into the lateral ventricle of a rat brain, the rat was killed and then the brain was removed. [3H]GABOB in the brain was identified by a combination of ion-exchange chromatography, high-voltage paper electrophoresis, and recrystallization of the radioactive compound with authentic GABOB.

Differentiating Enantioselective Actions of GABOB: A Possible Role for Threonine 244 in the Binding Site of GABAC ρ1 Receptors

“…4-Amino-3-hydroxybutanoic acid (GABOB) is an endogenous molecule found within the CNS, possessing anticonvulsant properties . It is formed by two metabolic pathways: either by the metabolism of putrescine to γ-aminobutyric acid (GABA) and then hydroxylation of GABA at the third carbon (C3), , or by the hydroxylation of putrescine to 2-hydroxyputrescine and then oxidative N-dealkylation to GABOB . There are conflicting results concerning the concentration of GABOB in the CNS, with concentration ranging between <0.01 and 4.8 μmol/g for rat and bovine brain, respectively.…”

“…1 It is formed by two metabolic pathways: either by the metabolism of putrescine to γ-aminobutyric acid (GABA) and then hydroxylation of GABA at the third carbon (C3), 2,3 or by the hydroxylation of putrescine to 2-hydroxyputrescine and then oxidative N-dealkylation to GABOB. 3 There are conflicting results concerning the concentration of GABOB in the CNS, with concentration ranging between <0.01 and 4.8 μmol/g for rat and bovine brain, respectively. However, the precursor to GABOB, 2-hydroxyputrescine, is found throughout the brain, and Noto and his colleagues have quantified the amount of 2-hydroxyputrescine in rat cerebellum (2.44 ± 0.49 pg/μg protein) and hippocampus (1.52 ± 0.20 pg/μg protein).…”