File:Fmolb-09-897929-g006.jpg

English: Overview of the mechanism regulating TDO stability in the liver to control blood tryptophanemia. Protein intake increases the blood level of tryptophan, which accumulates in hepatocytes (red color). High tryptophan levels stabilize the tetrameric conformation of TDO through the binding of tryptophan in four exosites, thereby stimulating tryptophan catabolism. When tryptophan becomes scarce (blue color), the absence of tryptophan binding the exosites destabilizes the tetrameric structure of TDO in inactive monomers and dimers. Absence of tryptophan unmasks a degron in the exosites, which triggers TDO ubiquitination by SKP1-CUL1-F-box complexes. This finally induces TDO degradation by the proteasome, thereby stopping tryptophan catabolism.