ISSN:
1471-4159
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Abstract: Δ′-Pyrroline, S-methyl-Δ′-pyrroline, and 5.5-dimethyl-Δ′-pyrroline have been identified as substances metabolized to γ-aminobutyric acid (GABA), 4-aminopentanoic acid (raethyl GABA), and 4-amino-4-methylpen-tanoic acid (dimethyl GABA), respectively. An enzyme system residing in the soluble fraction of rabbit liver catalyzes the conversion of Δ′-pyrroline to GABA and its lactam, 2-pyrrolidinone. Acetaldehyde, allopurinol, and cyanide inhibited the reaction. Incubation of deuterium-labeled Δ′-pyrroline with mouse brain homogenates produced deuterated GABA. Mouse liver 10,000 g supernatant and mouse brain homogenates converted S-methyl-Δ′-pyrroline to methyl GABA, and 5,5-dimethyl-Δ′-pyrroline to dimethyl GABA. Four hours after intraperitoneal injection of 5-methyl-Δ′-pyrroline (200 mg/kg), methyl GABA was detected in mouse brain (0.27 μ-mol/g). Dimethyl GABA (1.21 μmol/g) was determined in mouse brain 30 min after intraperitoneal administration of 5.5-dimethyl-Δ′-pyrroline (200 mg/kg). Neither methyl GABA nor dimethyl GABA penetrated into the central nervous system when administered in the periphery. The present studies suggest that pyrrolines may represent a chemical class of brain-penetrating precursors of pharmacologically active analogues of GABA.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1471-4159.1982.tb05348.x
