High levels of dietary protein or methionine have different effects on cysteine metabolism in rat hepatocytes.

This study clearly indicates that relatively high levels of both CDO and CSAD activity are needed for substantial taurine synthesis and that protein and methionine supplementation, at equimolar sulfur amino acid levels, are not equivalent in terms of their effects on cysteine catabolic enzyme activities and cysteine metabolism in hepatocytes. Evidence for a reciprocal regulation of cysteine catabolism (or CDO activity) and GSH synthesis (or gamma-glutamylcysteine synthetase activity) in rat liver was also obtained. Although very high levels of protein and methionine were fed in this study, previous studies with lower levels of protein or methionine showed similar changes in cysteine metabolism. Several questions regarding regulation of cysteine metabolism remain unanswered. Beyond sulfur amino acid availability, animals fed high protein diets appear to have other signals for regulation of CDO and CSAD activities. These signals may be related to the different hormonal and metabolic state of these animals. Furthermore, little is known about the molecular mechanisms involved in the observed changes in CDO and CSAD activities. The association between CDO activity and CDO protein has not been evaluated. Jerkins and Steele, using immunochemical detection and quantification of CSAD protein in rat liver, showed that changes in CSAD protein concentration were correlated to changes in CSAD activity. The exact mechanisms or direct effectors which bring about changes in CDO and CSAD activities have yet to be determined. Further exploration of these potential regulatory mechanisms needs to be conducted to better understand the response of cysteine sulfinate-dependent cysteine catabolism to high levels of dietary protein or sulfur amino acids.