REGULATION OF GLUTAMINASE ACTIVITY AND GLUTAMINE-METABOLISM

Glutamine is synthesized primarily in skeletal muscle, lungs, and adip ose tissue. Plasma glutamine plays an important role as a carrier of n itrogen, carbon, and energy between organs and is used for hepatic ure a synthesis, for renal ammoniagenesis, for gluconeogenesis in both liv er and kidney, and as a major respiratory fuel for many cells. The cat abolism of glutamine is initiated by either of two isoforms of the mit ochondrial glutaminase, Liver-type glutaminase is expressed only in pe riportal hepatocytes of the postnatal liver, where it effectively coup les ammonia production with urea synthesis. Kidney-type glutaminase is abundant in kidney, brain, intestine, fetal liver, lympho-cytes, and transformed cells, where the resulting ammonia is released without fur ther metabolism. The two isoenzymes have different structural and kine tic properties that contribute to their function and short-term regula tion. Although there is a high degree of identity in amino acid sequen ces, the two glutaminases are the products of different but related ge nes. The two isoenzymes are also subject to long-term regulation. Hepa tic glutaminase is increased during starvation, diabetes, and feeding a high-protein diet, whereas kidney-type glutaminase is increased only in kidney in response to metabolic acidosis. The adaptations in hepat ic glutaminase are mediated by changes in the rate of transcription, w hereas kidney-type glutaminase is regulated at a posttranscriptional l evel.