A novel glutaminase isoform in mammalian tissues

The synthesis of neurotransmitter glutamate in brain is mainly carried out by glutaminase enzymes. This synthesis must be exquisitely regulated because of its harmful potential giving rise to excitotoxic damage. It is noteworthy that two glutaminase isozymes coded by different genes are expressed in the brain of mammals. The need for two genes and two isozymes to support the single process of glutamate synthesis is unexplained, and identifying the role of each glutaminase is an important factor in understanding glutamate-mediated neurotransmission. Multiple transcripts for glutaminase genes and simultaneous expression of glutaminase isoforms have been reported in mammalian tissues and cells. The recent discovery of protein interacting partners widens the possibilities of regulatory mechanisms controlling these biosynthetic enzymes. The expression of distinct isozymes and binding partners may represent the biochemical and molecular basis to achieve fine-tuning control of glutamate synthesis in different cell types or developmental states. In this review, we will briefly summarize recent works on glutaminase proteins in mammals, with particular emphasis on brain studies. We present convergent evidence supporting the existence of a novel glutaminase isozyme in mammalian tissues.