Compartmentation of glutamate metabolism in brain. Evidence for the existence of two different tricarboxylic acid cycles in brain

1. ¹⁴C from [1−¹⁴C]glucose injected intraperitoneally into mice is incorporated into glutamate, aspartate and glutamine in the brain to a much greater extent than ¹⁴C from [2−¹⁴C]glucose. This difference for [1−¹⁴C]glucose and [2−¹⁴C]glucose increases with time. The amount of ¹⁴C in C-1 of glutamate increases steadily with time with both precursors. It is suggested that a large part of the glutamate and aspartate pools in brain are in close contact with intermediates of a fast-turning tricarboxylic acid cycle. 2. ¹⁴C from [1−¹⁴C]acetate and [2−¹⁴C]acetate is incorporated to a much larger extent into glutamine than into glutamate. An examination of the time-course of ¹⁴C incorporated into glutamine and glutamate reveals that glutamine is not formed from the glutamate pool, labelled extensively by glucose, but from a small glutamate pool. This small glutamate pool is not derived from an intermediate of a fast-turning tricarboxylic acid cycle. 3. It is proposed that two different tricarboxylic acid cycles exist in brain.