This investigation is interested in exploring how a single essential amino acid, specifically L-tryptophan, affects protein metabolism in the liver. In earlier reports from our laboratory we have described that L-tryptophan rapidly stimulates hepatic polyribosomal aggregation and protein synthesis. This effect appears to be related to alterations in both transcriptional and posttranscriptional controls. Our present proposal plans to explore at the cellular and subcellular levels how L-tryptophan may act, possibly directly on the nucleus (nuclear membrane), to stimulate enhanced nucleocytoplasmic translocation of mRNA. We plan to study in detail how proteins of the cytosol and nuclear membranes of the livers of tryptophan-treated rats are involved in the increased nucleocytoplasmic translocation of mRNA. In view of our recent findings that there are specific tryptophan binding sites on the nuclear envelopes of rat liver, we are now exploring the possible significance of the binding in relation to the enhanced nuclear RNA release in the liver due to tryptophan. We plan to characterize the structure and properties of the nuclear envelope tryptophan binding protein(s). Also we plan to determine whether the tryptophan specific binding may be affected by changes in the liver, such as induced by pretreatment of animals with a variety of hepatotoxic agents. Such information may offer basic insight as to how an important dietary component, as exemplified by L-tryptophan, may play a regulatory role in mammalian liver protein metabolism.
