The metabolism of L-tryptophan by isolated rat liver cells. Effect of albumin binding and amino acid competition on oxidatin of tryptophan by tryptophan 2,3-dioxygenase.
1. Novel methods, using L-[ring-2-14C]tryptophan, are described for the measurement of tryptophan 2,3-dioxygenase activity and tryptophan accumulation in isolated rat liver cells. 2. The effects of bovine serum albumin, non-esterified fatty acids and neutral amino acids on tryptophan oxidation by hepatocytes and on the partition of tryptophan between free and albumin-bound forms were investigated. 3. Oxidation of physiological concentrations (0.1 mM) of tryptophan was inhibited by approx. 50% in the presence of 2% (w/v) bovine serum albumin; no effects were found at tryptophan concentrations of 0.5 mM and above. 4. Increases in free tryptophan concentrations produced by displacement of 0.1 mM-tryptophan from albumin-binding sites by palmitate resulted in increased flux through tryptophan dioxygenase. 5. Addition of a mixture of neutral amino acids, at plasma concentrations, to hepatocyte incubations had no effect on the rate of tryptophan oxidation. 6. It is concluded that alterations in free tryptophan concentrations consequent to changes in albumin binding may be an important factor in regulating tryptophan uptake and catabolism by the liver. The results are briefly discussed with reference to possible consequences on brain tryptophan metabolism.
D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D010169:Palmitic Acids / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D014364:Tryptophan / Q000378:metabolism*; D014366:Tryptophan Oxygenase / Q000378:metabolism*
D000596:Amino Acids; D005230:Fatty Acids, Nonesterified; D010169:Palmitic Acids; D012710:Serum Albumin, Bovine; D014364:Tryptophan; D014366:Tryptophan Oxygenase