Oxygenase, mixed function type

Since the formation of the ethyleniminium ion is crucial for the cytotoxic activity of the nitrogen mustards, it is not surprising that stable ethylenimine derivatives have antitumor activity. Thiophospho-ramide or thiotepa is the best known compound of this type that has been used clinically. Both thiotepa and its primary metabolite, triethylenephos-phoramide (TEPA), to which it is rapidly converted by hepatic mixed-function oxygenases form crosslinks with DNA. It is mainly used as an intravesicu-lar agent in bladder cancer. Thiotepa produces little toxicity other than myelosuppression. 

Arachidonic acid can also be metabolized to a variety of mediators, depending on the cell type. For example, lipoxygenase catalyzes the production of leu-kotrienes, and mixed-function oxygenases catalyze the production of epoxyeicosatrienoic acids. Collectively, these oxygenated metabolites may play a critical role in NSAIEt-induced nephrotic syndrome by shunting arachidonic acid metabolism from prostaglandins to... 

The NADPH-cytochrome P-450 system, commonly known as the mixed-function oxygenase (MFO) system, is the most important enzyme system involved in the Phase I oxidation reactions. Cytochrome P-450 system, localized in the smooth endoplasmic reticulum of cells of most mammalian tissues, is particularly abundant in the liver. This system contains a number of isozymes which are versatile in that they catalyze many types of reactions including aliphatic and aromatic hydroxylations and epoxidations,... 

The second type of enzyme was, therefore, referred to as a mixed function oxygenase or mixed function oxidase because, as will be described later, these enzymes are bifunctional, carrying out oxidase activity on one site and oxygenase activity on the other. Recently the term hydroxylase has been preferred to mixed function oxidase or mixed function oxygenase, presumably because the former is more concise and convenient (Massart and Vercauteren, 1959). 

The term hydroxylase, or mixed function oxygenase, denotes an enzyme which catalyzes the incorporation of one atom of atmospheric oxygen into various substrates. As shown in Eq. (17), this type of reaction is characterized by a somewhat paradoxical pair of requirements (i) oxygen is necessary, as a specific oxidizing agent, and (ii) an election donor is needed, as a reductant. One of the oxygen atoms is incorporated into the substrate molecule, while the other atom is presumed to be simultaneously reduced to water. 

---