Oxygenase enzymes

Enzymes that directly incorporate molecular oxygen into organic substrates play a crucial role in many fundamental biological processes such as degradation of natural products in the biosphere, biosynthesis and metabolism of amino acids, hormones, drugs, etc. A wide variety of enzymic oxygenases has been identified and isolated from microorganisms, plants and animals. A detailed description of these enzymes is beyond the scope of this chapter, but several books and review articles are available.1,58-62... 

Other experiments with Gibberellafujikuroi the fungus that produces gibbereUin, indicate that GA production is blocked by BAS 111. Very detailed and carehil experiments conducted with enzymes in ceU-free systems strongly support this mode of action, ie, using /-kaurene oxidase and cinnamate 4-mono-oxygenase isolated from pea apices and soybean suspension cells, and avanone-2-hydtoxylase and dibydroxypterocarpane 6-hydtoxylase from soybean suspension cells (31). 

Nothing is known about the identity of the iron species responsible for dehydrogenation of the substrate. Iron-oxo species such as FeIV=0 or Fem-OOH are postulated as the oxidants in most heme or non-heme iron oxygenases. It has to be considered that any mechanistic model proposed must account not only for the observed stereochemistry but also for the lack of hydroxylation activity and its inability to convert the olefinic substrate. Furthermore, no HppE sequence homo-logue is to be found in protein databases. Further studies should shed more light on the mechanism with which this unique enzyme operates. 

P450 Mono-Oxygenase System P450 Enzymes... 

Cytochrome P450 (CYP) mono-oxygenases, also called mixed function oxidases, are versatile hemoprotein enzymes that catalyze the cleavage of molecular oxygen to incoiporate one oxygen atom into a substrate molecule and one atom into water [1]. The general stoichiometry of the reaction is as follows (S-H, substrate) ... 

Oxygenases are concerned with the synthesis or degradation of many different types of metabolites. They catalyze the incorporation of oxygen into a substrate molecule in two steps (1) oxygen is bound to the enzyme at the active site, and (2) the bound oxygen is reduced or transferred to the substrate. Oxygenases may be divided into two subgroups, as follows. 

Catabohsm of the heme ring is initiated by the enzyme heme oxygenase, producing a hnear tetrapyr-role. 

These include the mitochondrial respiratory chain, key enzymes in fatty acid and amino acid oxidation, and the citric acid cycle. Reoxidation of the reduced flavin in oxygenases and mixed-function oxidases proceeds by way of formation of the flavin radical and flavin hydroperoxide, with the intermediate generation of superoxide and perhydroxyl radicals and hydrogen peroxide. Because of this, flavin oxidases make a significant contribution to the total oxidant stress of the body. 

The major mono oxygenases in the endoplasmic reticulum are cytochrome P450s—so named because the enzyme was discovered when it was noted that preparations of microsomes that had been chemically reduced and then exposed to carbon monoxide exhibited a distinct peak at 450 nm. Among reasons that this enzyme is important is the fact that approximately 50% of the drugs humans ingest are metabolized by isoforms of cytochrome P450 these enzymes also act on various carcinogens and pollutants. 

Carotene cleavage enzymes — Two pathways have been described for P-carotene conversion to vitamin A (central and eccentric cleavage pathways) and reviewed recently. The major pathway is the central cleavage catalyzed by a cytosolic enzyme, p-carotene 15,15-oxygenase (BCO EC 1.13.1.21 or EC 1.14.99.36), which cleaves p-carotene at its central double bond (15,15 ) to form retinal. Two enzymatic mechanisms have been proposed (1) a dioxygenase reaction (EC 1.13.11.21) that requires O2 and yields a dioxetane as an intermediate and (2) a monooxygenase reaction (EC 1.14.99.36) that requires two oxygen atoms from two different sources (O2 and H2O) and yields an epoxide as an intermediate. ... 

Wyss, A., Carotene oxygenases a new family of double bond cleavage enzymes, J. Nutr. 134, 246S, 2004. 

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