The metabolism of dietary sulfur as sulfur amino acids is altered during conditions of depressed liver function. The marked elevation in tissue methionine and the appearance of methyl mercaptan and alpha-aminobutyrate during liver disease suggests an alteration in sulfur nutrition via the process of transsulfuration. Studies will be conducted to determine the effect of experimental liver dysfunction and dietary protein level on dietary sulfur oxidation to urinary sulfate, taurine and total urinary sulfur from methionine and cysteine. Comparisons of relative rates of transsulfuration in normal rats and in rats subjected to experimental liver dysfunction will be determined using a 3H and 35S doubly labeled methionine infusion and isolation and counting of tissue proteins to determine if the process of sulfur transfer from methionine to cysteine is altered during decreased hepatic function. The production of methyl mercaptan in patients and experimental animals is correlated with deterioration of liver function. Blood volatile sulfur compounds will be monitored by gas chromatography in rats with depressed liver function and maintained on diets with low, moderate or high levels of protein/methionine. In addition, a new method for blood methyl mercaptan (total) will be developed utilizing a diffusion assay for labile alkylthio groups released from blood by treatment with reducing agents. This assay should prove superior to existing methodology since methyl mercaptan in blood is probably also present in the form of dimethyl disulfide and in mixed disulfide linkage with normal blood sulfur such as glutathione and protein sulfhydryl. A derivative of the carbon skeleton of methionine, alpha-aminobutyrate, is found in elevated levels during decreased liver function. Alpha-aminobutyrate metabolism will be studied in rats with altered liver function to determine if the reason for increased levels of this compound is due to an impairment in alpha-keto acid oxidation (i.e., alpha-ketobutyrate) or due to an enhanced rate of catabolism of methionine or threonine, its metabolic precursors.
