Tryptophan pyrrolase oxygenase

The focus of this chapter is the reaction site of oxygenases (hemo-proteins) having heme as the prosthetic group. We discuss the oxygen activation in tryptophan pyrrolase (TPO) and cytochrome P-450 based on our experimental results using iron-porphyrin complexes as the model for the active site of these enzymes. 

The first enzyme of the pathway, tryptophtm dioxygenase (edso known as tryptophan oxygenase or tryptophan pyrrolase), is rate -limiting under normal conditions. In isolated hepatocytes, the control coefficient for flux through the pathway of tryptophan dioxygenase is 0.75 tmd that for tryptophan upttike into the cells is 0.25 (Salter et til., 1986). 

The dioxygenases, which incorporate two atoms of oxygen into one molecule of the substrate, are enzymes which are frequently involved in the cleavage of bonds in an aromatic ring. Typical of these are homogentisate oxidase and L-tryptophan oxidase (L-tryptophan pyrrolase) and two bacterial oxygenases pyrocatechase and metapyrocatechase. ... 

Tryptophan oxygenase (tryptophan pyrrolase) plays an important role in the metabolism of tryptophan and has been prepared from animal tissues (Knox and Mehler, 1950) and bacteria (Hayaishi and Stanier, 1951). Enzymes from the two sources were found to be comparable in many respects. Knox and Mehler named the enzyme tryptophan peroxidase-oxidase, since they had found that catalase inhibits the reaction and that this inhibition is reversed by hydrogen peroxide, suggesting the intermediate formation and the subsequent utilization of peroxide as shown in Eqs. (21) and (22). 

If the enzymes that oxidize indoleacetic acid are found in general to utilize nonspecific electron acceptors in the presence of hydrogen peroxide, it must be concluded that the mechanism of indoleacetic acid oxidation is primarily a peroxidation, not an oxygenation. At the present time, however, the possibility must also be considered that the role of hydrogen peroxide and substrate is to establish the ferrous state of the enzyme required for oxygenase activity, as in the case of tryptophan pyrrolase. 

---