Studies with compounds that compete with tryptophan binding to rat hepatic nuclei.
Tryptophan has been demonstrated to affect hepatic RNA and protein metabolism. Binding of tryptophan to nuclear envelope proteins has been demonstrated to be saturable, stereospecific, and of high affinity. The hepatic nuclear envelope tryptophan binding protein (glycoprotein) has been purified to apparent homogeneity using either concanavalin A-agarose or tryptophan-agarose. The receptor has an Mr of approximately 34,000, which is the same as that observed when [3H]tryptophan has been crosslinked to nuclear proteins. In this study, we investigated whether analogs, metabolites or related compounds of tryptophan as well as other amino acids may bind to rat hepatic nuclei using in vitro [3H]tryptophan binding assays. Our results indicate that compounds that compete with [3H]tryptophan binding to hepatic nuclei or nuclear envelopes contain the alpha-amino-propionic acid structure. Such compounds were 5-fluoro tryptophan, 7-aza tryptophan, 5-hydroxy tryptophan, alanine, phenylalanine, tyrosine, cysteine and cystine. It was of interest that, whereas tryptophan-methyl ester and tryptophan-ethyl ester competed, alpha-methyl tryptophan, N-formyl tryptophan, N-acetyl tryptophan, and N-methyl tryptophan did not compete with [3H]tryptophan binding to hepatic nuclei or nuclear envelopes. Nonetheless, only the in vivo administration of L-tryptophan was able to stimulate nucleocytoplasmic efflux of hepatic RNA and protein synthesis.
Department of Pathology, George Washington University Medical Center, Washington, DC 20037.
H
H
Sidransky
E
E
Verney
J W
JW
Cosgrove
A M
AM
Schwartz
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D005260:Female; D008099:Liver / Q000378:metabolism*; D009685:Nuclear Envelope / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014364:Tryptophan / Q000031:analogs & derivatives / Q000378:metabolism*
D000596:Amino Acids; D012313:RNA; D014364:Tryptophan