The uptake and metabolism of (U-I4C) L-omithine by several cellular preparations was examined and compared to corresponding data for glutamine and a-ketoglutarate. Five fractions were obtained from the cerebellum of 10-to 14-day-old mice; two fractions were enriched in astrocyte cell bodies, whereas one was comprised primarily of granule cell bodies, and another was enriched in nerve terminals. Metabolic studies were also conducted on two synaptosomal preparations prepared from rat cerebral tissue.
The uptake of ornithine by the cerebellar fractions was mediated by one or two saturable transport systems with apparent K,,, values between 50 and 200 FM. Uptake inhibition experiments indicated that ornithine is transported primarily, if not exclusively, by the basic amino acid carrier@), and that glutamine is transported in part by this carrier. Ornithine was metabolized to proline, glutamate, and to a lesser extent aspartate, glutamine and GABA. Under the conditions of our experiments, the cell bodies metabolized ornithine somewhat more readily than did the nerve terminal enriched fraction obtained from the mouse cerebellum. Our data indicate that the conversion of ornithine to GABA occurs predominantly, if not exclusively, via the pathway involving glutamate rather than putrescine. In comparison to data for glutamine and a-ketoglutarate, the metabolism of omithine to glutamate was slow.
Although the results of our study are consistent with the hypothesis that ornithine serves as a metabolic precursor of the neurotransmitter pools of glutamate and GABA, our data do not support a major role for omithine in this capacity. Based on a comparison of the availability of omithine, glutamine and a-ketoglutarate, and the rates at which they are each transported into synaptosomes and metabolized therein to glutamate and GABA, our data suggest that glutamine and a-ketoglutarate are used more extensively to replenish these transmitter pools.