Dioxygenase, enzyme reactions

Oxygenation and hydroxylation of a wide variety of biological materials almost always involves the participation of a metal ion, usually iron and sometimes copper. In one unique case, tryptophane pyrrolase, the iron is present as heme (75). The only dioxygenase enzyme reaction in which a metal ion has not been implicated is one involved in the degradation of vitamin B6 (16). 

What is remarkable, however, is the stereochemical influence of a 13-hydroxyl group, p-hydroxycarbocations such as 31 are formed not only from arene oxide as precursors but from arene dihydrodiols. As shown for the parent benzene dihydrodiols in Scheme 23, arene dihydrodiols exist as cis-and /ra/rv-isomers. The m-isomers are obtained as products of the action on the aromatic molecule of dioxygenase enzymes and have been prepared on a large scale by fermentation.92 The trans-isomers are normally accessible by straightforward synthesis, for example, from the arene oxide. Both isomers undergo acid-catalyzed dehydration to the parent aromatic molecule, as is also shown in Scheme 23. It is clear that their reactions should involve a common carbocation intermediate,163 164 and in so far as there is little difference in the stabilities of the isomers,165 their difference in reactivities might have been expected to be small. 

These studies show that activated oxygen can effect the reactions catalyzed by the a-ketoacid dioxygenases and suggest that the ferrous ion may function as an activator of molecular oxygen in these enzyme reactions. 

The reaction of nonheme Fe complexes that are analogues of Rieske dioxygenase enzymes have been studied by the group of Que [234,235] (see Chapter 18). A possible mechanism has been suggested [241] (Fig. 1.31) for a bispidme ligand. An [Fe oOH] intermediate is formed initially, which undergoes 0-0 bond homolysis to form a ferryl [Fe =O] oxidant and HO. The oxidant was formed independently by reaction of the complex with lodosylbenzene as indicated by the appearance of an expected electronic transition in the near infrared of e = 400 M cm . This was able to epoxidize czs-cyclooctene in an Ar atmosphere. 

The dioxygenation of unsaturated a-diols (catechol and benzoin. Table 6-2) by the O2/Fe l(DPAH)2 system parallels that of the catechol dioxygenase enzymes, which are nonheme iron proteins. -l Hence, the reactive intermediate (1, Scheme 6-1) of the Feh(DPAH)2/O2 reaction may be a useful model and mimic for the activated complex of dioxygenase enzymes. ... 

In the reaction catalyzed by HPPD, the a-keto acid used for oxidative decarboxylation is in the substrate molecule. Interestingly, another dioxygenase enzyme also uses the same substrate to catalyze a different... 

The bacterial degradation of quinoline heterocycles proceeds via oxidation to 3-hydroxy-4-oxoquinolines, which are substrates for a novel family of dioxygenases. The reaction is similar to the copper-dependent quercetin dioxygenase (see Section 8.16.4.2), involving oxidative cleavage of two C—C bonds, and liberation of carbon monoxide however, remarkably, these enzymes have no cofactor requirement. Two dioxygenases QDO... 

In summary, a range of oxidative cleavage reactions, catalyzed by dioxygenase enzymes, have been identified, that are involved in catabolic and biosynthetic pathways. While the majority of these enzymes require nonheme iron as cofactor, several examples of copper-dependent or cofactor-independent dioxygenases have come to light, whose mechanisms for oxygen activation and catalytic mechanism share several features with the nonheme iron-dependent dioxygenases. 

Scheme 1. The reaction catalyzed by the heme dioxygenase enzymes.

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