STUDY OF THE METABOLISM OF 2-HYDROXY-4-AMINOBUTYRIC ACID, A PRODUCT OF γ-HYDROXYGLUTAMIC ACID DECARBOXYLATION

Abstract

The isotope technique was used to study the metabolism, in rat tissues, of 2-hydroxy-4-aminobutyric acid (HABA), which is known to be formed in the brain by decarboxylation of γ-hydroxyglutamic acid. A method is described for the synthesis of DL-HABA-4-14C by using K14CN and ethyl 3-bromopropionate as starting materials. The high rate of radiocarbon excretion observed in the expired CO2of rats injected intravenously with the labeled amino acid is an indication that it is extensively degraded in the animal organism. Whereas enterectomy did not appreciably decrease the utilization of HABA, hepatectomy caused a pronounced lowering of the radiocarbon excretion. Paper radiochromatograms of the deproteinized blood plasma indicated the presence of malate as a major catabolite. Further evidence for the formation of malic acid was obtained from the incubation of DL-HABA-4-14C in the presence of rat brain or liver homogenates, enriched with L-malate, α-ketoglutarate, and pyridoxal phosphate. We believe that HABA is deaminated by transamination to malate semialdehyde, which is then oxidized to malate.