13N as a tracer for studying glutamate metabolism

▶ In the liver GDH and aminotransferases incorporate or remove ammonia from amino acids. ▶ In the brain GDH is a source of ammonia for glutamine synthesis. ▶ Incorporation of ammonia into glutamine amide in the rat brain is rapid ( t 1/2 ≤ 3 s). ▶ Exchange of nitrogen among ammonia, glutamate and aspartate in liver and brain is rapid. This mini-review summarizes studies my associates and I carried out that are relevant to the topic of the present volume [i.e. glutamate dehydrogenase (GDH)] using radioactive 13N ( t 1/2 9.96 min) as a biological tracer. These studies revealed the previously unrecognized rapidity with which nitrogen is exchanged among certain metabolites in vivo. For example, our work demonstrated that (a) the t 1/2 for conversion of portal vein ammonia to urea in the rat liver is ∼10–11 s, despite the need for five enzyme-catalyzed steps and two mitochondrial transport steps, (b) the residence time for ammonia in the blood of anesthetized rats is ≤7–8 s, (c) the t 1/2 for incorporation of blood-borne ammonia into glutamine in the normal rat brain is