Pyrrolooxygenases: A new type of oxidases
- 20 Downloads
A new type of oxygenases was isolated from plant and animal sources which oxidized pyrrole and indole derivatives. They had a broad substrate specificity and were called pyrrolooxygenases. Three different enzymes within the group were identified; skatole pyrrolooxygenase, tryptophan pyrrolooxygenase and porphobilinogen oxygenase. The first two oxidized the pyrrole ring of the various indole derivatives affording substituted o-formanidophenacyl derivatives as the main oxidation products. Tryptophan pyrrolooxygenase also oxidized the tryptophanyl residues of peptides and enzymes. When those residues were essential for the activity of the tryptophan containing enzymes, then inactive enzymes were obtained.
Porphobilinogen oxygenase oxidized porphobilinogen and related alkylpyrrole compounds affording 3-pyrrolin-2-one derivatives. The pyrrolooxygenases acted as mixed-function oxidases, since they required the presence of oxygen and of a reducing agent. The substrate, the oxygen and the reductant were consumed in equimolar amounts. The best artificial reducing agent was sodium dithionite. Illuminated active chloroplasts were the natural reducing agent of the plant enzymes and NADPH was the reducing agent of the animal enzymes. Pyrrolooxygenases were located in the chloroplasts of green leaves and in the microsomes in the case of the mammalian enzymes. The activity of the enzymes in the crude extracts was usually low, due to the presence in the same of a protein inhibitor. When the inhibitor was separated by protein fractionation methods, full enzymatic activity was recovered. Destruction of the inhibitor by aging or by temperature had the same effect. The very low oxygenase activity present in the microsomal rat liver preparations could be strongly enhanced by previous administration to the rats of phenobarbital or steroids. This induction of the oxygenase activity was coincident with a drop in the amount of inhibitor present in the extracts.
The properties and metabolic role of the pyrrolooxygenases are discussed.
KeywordsPyrrole Dithionite Sodium Dithionite Indole Derivative Porphobilinogen
Unable to display preview. Download preview PDF.
- D. G. Irvine, W. Bayne, H. Miyashita and J. B. Majer, Nature, 224, 811–813 (1969); D. G. Irvine and L. Wetterberg, Lancet, 1201 (1972).Google Scholar
- B. S. Deol, J. R. Alden, J. L. Still, J. Winkler and A. V. Robertson, Biochem. Biophys. Res. Comm., 47(6), 1378–1385 (1972).Google Scholar
- J. Awruch and B. Frydman, Tetrahedron Lett., 2611 (1973).Google Scholar
- G. B. Quistad and D. A. Lightner, Tetrahedron Lett., 46, 4417–4420 (1971).Google Scholar
- E. Hoft, A. R. Katrizky and M. R. Nesbit, Tetrahedron Lett., 32, 3041–3044 (1967).Google Scholar
- B. Witkop and H. Fiedler, Liebig's Ann. Chem., 558, 91–96 (1947).Google Scholar
- R. Tenhunen, H. Marver, N. R. Pimstone, W. F. Trager, D. Y. Cooper and R. Schmid, Biochemistry, 11 (9), 1716 (1972).Google Scholar
- F. Hirata and O. Hayaishi, Biochem. Biophys. Res. Comm., 47, 1112; and references therein (1972).Google Scholar
- R. B. Frydman, M. L. Tomaro and B. Frydman, FEBS (Fed. Europ. Biochem. Soc.) Lett. 15, 305–308 (1971).Google Scholar
- R. B. Frydman, M. L. Tomaro and B. Frydman, Biochim. Biophys. Acta, 284, 63–79 (1972).Google Scholar
- R. B. Frydman, M. L. Tomaro, A. Wanschelbaum and B. Frydman, FEBS (Fed. Europ. Biochem. Soc.) Lett., 26, 1, 203–206 (1972).Google Scholar
- G. A. Hamilton, Adv. in Enzymology, 32, 55–96 (1968).Google Scholar
- D. M. Jerina, J. W. Daly, B. Witkop, P. Zaltzman-Nirenberg and S. Udenfriend, Biochemistry, 9, 147–156 (1970).Google Scholar
- C. E. Dalgliesh, Biochem. J. 61, 334–337 (1955).Google Scholar
- H. Kaseda, T. Noguchi, R. Kido and Y. Matsumora, Experientia, 26, 828–829 (1970).Google Scholar
- H. Kaseda, T. Noguchi, N. Tonishi and R. Kido, Experientia, 27, 368–369 (1971).Google Scholar
- R. B. Frydman, M. L. Tomaro and B. Frydman, Biochim. Biophys. Acta, 284, 80–89 (1972).Google Scholar
- A. Patchornik, W. B. Lawson, E. Gross and B. Witkop, J. Am. Chem. Soc., 82, 5923–5927 (1960).Google Scholar
- R. B. Frydman and B. Frydman, Arch. Biochem. Biophys. 136, 193–202 (1970).Google Scholar
- R. B. Frydman and B. Frydman, Biochim. Biophys. Acta, 293, 506–513 (1973).Google Scholar
- H. Holzer and W. Duntze, Annu. Rev. Biochem., 40, 345–374 (1971).Google Scholar
- B. Peterkofsky and S. Udenfriend, J. Biol. Chem., 238, 3966–3977 (1963).Google Scholar
- D. G. Irvine, W. Bayne and H. Miyashita, Canadian Fed. of Biol. Soc.; in press (1973).Google Scholar
- F. De Matteis, Pharmacol. Rev., 19 (4), 523–538 (1967).Google Scholar
- L. Kaufman, A. L. Swanson and H. S. Marver, Science, 170, 320 (1970).Google Scholar