(taken directly from the application) This application presents experiments analyzing molecular mechanisms underlying nutritional and hormonal regulation of cysteine dioxygenase (CD) and cysteine sulfinic acid decarboxylase (CSAD), key enzymes in taurine biosynthesis. Taurine is highly concentrated in brain, heart and retina and its deficiency is associated with cardiomyopathy, retinal degeneration, and abnormalities in central nervous system development. Cysteine dioxygenase converts cysteine to cysteine sulfinic acid which can then become a substrate in the pyruvate and sulfate producing pathway or, alternatively, in the taurine producing pathway. Cysteine sulfinic acid decarboxylase converts cysteine sulfinic acid to hypotaurine which then becomes taurine; thus, the regulation of CD and CSAD affect how much cysteine will become taurine or pyruvate and sulfate and the relative amounts that will become each of these products. Cysteine dioxygenase and CSAD appear to be reciprocally regulated by the amount of protein and/or sulfur amino acids in the diet, and increasing these nutrients increases CD activity and decreases CSAD activity, thereby leading to an increase in the production of sulfate and pyruvate, as compared to taurine, from cysteine. In addition, CD and CSAD are regulated by hormones. Adrenal hormones are required for dietary induction of hepatic CD activity but not for dietary depression of CSAD activity. The steroid hormone superfamily is involved in regulation of CD and CSAD as well. Both triiodothyronine and estradiol appear to decrease CSAD activity. The applicant plans to examine the molecular levels at which these nutrients and hormones regulate CD and CSAD activity. She plans to determine the effect of sulfur amino acids and hormones on steady state CD and CSAD mRNA, on the rates of CD and CSAD gene transcription, and on CD and CSAD mRNA stability. She will use a rat model for in vivo studies and cultured cell lines for in vitro studies. Next, she plans to clone and characterize the genes coding for CD and CSAD mRNAs in order to be in a position to accomplish her long- term goal of identifying regulatory sequences involved in nutrient and hormonal modulation of these genes.
| Chai, Sergio C; Jerkins, Ann A; Banik, Jacob J et al. (2005) Heterologous expression, purification, and characterization of recombinant rat cysteine dioxygenase. J Biol Chem 280:9865-9 |
| Jerkins, A A; Jones, D D; Kohlhepp, E A (1998) Cysteine sulfinic acid decarboxylase mRNA abundance decreases in rats fed a high-protein diet. J Nutr 128:1890-5 |
