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. Earlier studies at the cellular and subcellular levels have revealed that L-tryptophan acts on the hepatic nucleus (nuclear membrane) to stimulate enhanced nucleocytoplasmic translocation of mRNA Recent findings have demonstrated that there is a specific tryptophan-binding site on the nuclear envelopes of rat liver. This 64 kDa glycoprotein receptor for L-tryptophan has been purified and characterized. We plan to further characterize (composition, active structure and function) the 64 kDa glycoprotein purified as the hepatic nuclear envelope tryptophan binding protein. This will be conducted using purified rat hepatic nuclear envelope tryptophan binding protein as well as using cloned fusion protein. Since tryptophan rapidly stimulates hepatic nuclear poly(A)polymerase activity and since we have determined a close association between this enzyme and the tryptophan receptor protein, we plan to define the relationship between the two. We consider the receptor binding of tryptophan and the enhancement of poly(A)polymerase activity due to tryptophan to be important and vital components in the tryptophan-induced stimulation of hepatic protein synthesis. 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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
1R01DK045353-01
Application #
3246867
Study Section
Chemical Pathology Study Section (CPA)
Project Start
1992-09-30
Project End
1995-09-29
Budget Start
1992-09-30
Budget End
1993-09-29
Support Year
1
Fiscal Year
1992
Total Cost
Indirect Cost
Name
George Washington University
Department
Type
Schools of Medicine
DUNS #
City
Washington
State
DC
Country
United States
Zip Code
20052
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