Direct Assessment of Increased Pyruvate Carboxylase in the Hyperammonemic Brain using 13C MRS

Bernard Lanz¹, Cristina Cudalbu¹, Joo Miguel Duarte¹, Rolf Gruetter^1,2

Dynamic ¹³C MRS using [1,6-¹³C₂] glucose allows non-invasive measurement of the neuroglial metabolism in vivo. In this study, we coupled [1,6-¹³C₂] glucose with ammonium chloride infusion in rats in order to assess the effect of hyperammonemia on neuronal metabolism. While total glutamine was linearly increasing, the glutamine ¹³C enrichment curves were nevertheless reaching a dynamic steady-state in about 4 hours. From the fractional enrichment at steady-state of GluC4, GlnC4, GluC3 and GlnC3, we conclude that neuronal metabolism is hardly effected by hyperammonemia, while the glial pyruvate carboxylase activity increases significantly, as visible on the strongly diluted GlnC3.