Dr. Jang-Yen Wu Grant Application (IBN-9723079) - Regulation of Taurine Biosynthesis in the Brain Taurine (2-amino-ethanesulfonic acid), a sulfur amino acid with a simple chemical structure, is one of the most abundant amino acids in mammals. The physiological role of taurine has received considerable attention since the reports that cats fed a taurine deficient diet developed visual impairment, abnormality in brain development and heart function. Now, taurine has been shown to be involved in many important physiological functions e.g., as a trophic factor in the development of the central nervous system, maintaining the structural integrity of the cell, regulating calcium homeostasis, and modulation of communication between nerve cells. Despite its importance, the mechanisms involved in the regulation of taurine formation in the brain remain elusive. Taurine may be formed in biological systems by several routes. The major route of taurine formation in the brain is by converting sulfur-containing amino acids such as methionine and cysteine to cysteinesulfinic acid (CSA) and subsequent conversion of CSA to taurine. The catalysts used in biological systems are called enzymes. The particular enzyme involved in converting CSA to taurine is called cysteinesulfinic acid decarboxylase (CSAD). Recently, it was found that the activity of CSAD to synthesize taurine is altered when the structure of CSAD is modified. Specifically, CSAD activity is enhanced when a phosphate is attached to certain amino acids in CSAD molecule while CSAD activity is suppressed when the phosphate group is removed from CSAD molecule. The proposal is designed to understand the mechanisms involved in the regulation of CSAD activity. Some of the questions to be addressed are: (1) What are the biological catalysts involved in adding or removing phosphate group to or from CSAD molecules? (2) What are the amino acid residues in CSAD responsible for CSAD activity? (3) Are the changes of CSAD structure related to the state of the brain functions? Information obtained from the proposed studies should shed new light regarding the mechanism involved in the regulation of taurine biosynthesis in the brain. In addition, it may also provide a better understanding of the function of this important substance in the mammalian nervous system.
