On the role of GABA in vertebrate polyamine metabolism

Abstract

4-Aminobutyric acid (GABA), the major inhibitory neurotransmitter in vertebrate brain, is formed not only by decarboxylation of glutamic acid but also directly from putrescine. Two pathways can be shown to operate in vertebrates: oxidative deamination by diamine oxidase and transformation of putrescine into monoacetylputrescine with subsequent oxidative deamination of this intermediate by monoamine oxidase. Monoacetylation and oxidation degradation of the acetyl derivatives is most probably a common pathway of the polyamines. The formation of spermic acid and putreanine from spermine and spermidine, respectively, seems analogous to the reaction of putrescine with diamine oxidase. Apart from metabolic transformation of the polyamines to GABA, there are indirect interrelations with potential regulatory functions. A variety of agents able to influence brain GABA metabolism induce changes of the activity of the decarboxylases involved in polyamine metabolism and alterations of cerebral putrescine concentrations. These interrelations could be important in the control of local cerebral protein metabolism. The excessive transformation of putrescine to GABA in early neural development suggests a role in cellular differentiation.