Steroid oxygenases

Oxidoreductases have a variety of functions in metabolism oxidases and dehydrogenases play major roles in respiration hydroperoxidases protect the body against damage by free radicals and oxygenases mediate the hydroxylation of drugs and steroids. 

LTB4 is a potent bronchoconstrictor, as are several other leukotrienes. A 5-lip-oxygenase inhibitor, Zileuton, is approved for therapy of asthma (though it is not much used for this purpose) as is a leukotriene blocker, montelukast, marketed as Singulair. Singulair is widely used by asthmatics as a preventive for asthma attacks. Certain corticosteroids are employed for the same purpose. Neither montelukast nor the steroids are effective in terminating an established asthmatic attack. Beta agonists are employed for that purpose (see chapter 17). 

Celecoxib, a non-steroidal anti-inflammatory drug, is a cyclo-oxygenase-2 selective inhibitor that is as effective as diclofenac and naproxen. It should be used for the shortest period required to control symptoms. Use is associated v/ith an increased risk of thrombotic events and the cyclo-oxygenase-2 selective inhibitors are contraindicated in cerebrovascular disease. Mobic is the proprietary preparation of meloxicam. 

Mobic is the proprietary preparation of meloxicam, a non-steroidal antiinflammatory drug, which is also a selective inhibitor of cyclo-oxygenase-2. It is therefore less likely to cause gastrointestinal side-effects than other nonsteroidal anti-inflammatory drugs. However, it is still best to administer meloxicam after food. 

Indometacin, which is a non-steroidal anti-inflammatory drug, inhibits the enzyme cyclo-oxygenase implicated in inflammatory reactions. Indometacin is more effective as an anti-inflammatory agent than ibuprofen and tends to have a higher side-effect profile, including headache, diarrhoea and gastrointestinal disturbances. Rectal administration reduces but does not prevent gastrointestinal tract disturbances. 

Naproxen, a non-steroidal anti-inflammatory drug, inhibits prostaglandin release through inhibition of the cyclo-oxygenase-2 enzyme, producing an analgesic and anti-inflammatory effect. 

Renal clearance is usually decreased. Renal blood flow in particular is often poised critically and the use of, for example, a non-steroidal anti-inflammatory drug may cause heart failure and/or renal failure in people with existing cardiac conditions or some preexisting degree of chronic renal failure. These non-selective inhibitors of the cyclo-oxygenase enzyme... 

Kearney PM, Baigent C, Godwin J, HaUs H, Emberson JR, Patrono C. Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis Meta-analysis of randomised trials. BMJ 2006 332(7553) 1302-8. 

The mono-oxygenases which catalyse a series of oxidations such as hydroxylation, epoxidation, heteroatom oxidation and Baeyer-Villiger oxidation (Figure 2.24), depend on NADH or NADPH and cofactors usually Fe or Cu. A particularly important reaction is the direct incorporation of molecular oxygen into non-activated carbon centres, such as in synthesis of important steroidal drags by microbial 11 dr-hydroxylation of... 

Graham, D. J., D. Campen, R. Hui, M. Spence, C. Cheetham, G. Levy, S. Shoor, and W. A. Ray. 2005. Risk of Acute Myocardial Infarction and Sudden Cardiac Death in Patients Treated With Cyclo-oxygenase 2 Selective and Non-selective Non-steroidal Anti-inflammatory Drugs Nested Case-control Study. Lancet 365 475M81. 

Other names Homoprotocatechuate oxygenase Protocatechuate 4,5-oxygenase Steroid 4,5-dioxygenase 3-Alkylcatechol 2,3-dioxygenase... 

Redox components of adrenal steroid hydroxylase. In biological and chemical aspects of oxygenases, p. 179. K. Bloch and O. Hayaishi, ed. Tokyo Maruzen 1966. 

Non-steroidal anti-inflammatory agents, including ibuprofen and selective Cox-2 inhibitors (cyclo-oxygenase 2), can increase plasma lithium concentrations add with caution to patients stabilized on lithium... 

The Baeyer-Villiger reaction is also effected by biochemical oxidation using the enzyme cyclohexanone oxygenase from Acinetobacter strain NCIB 9871. Cyclohexanone is thus converted into e-caprolactone [1043], and phenylacetone (l-phenyl-2-propanone) is transformed into benzyl acetate. The formation of benzyl acetate from phenylacetone involves the same migration as that in oxidation with peroxytrifluoroacetic acid (equation 387) [1034]. More examples of biochemical Baeyer-Villiger reactions occur in diketones and steroids see equation 397). 

Sawdy R, Slater D, Fisk N, Edmonds DK, Bennett P. Use of a cyclo-oxygenase type-2-selective non-steroidal antiinflammatory agent to prevent preterm delivery. Lancet 1997 350(9073) 265-6. 

Hippisley-Cox J, Coupland C, Hippisley-Cox J, Coupland C. Risk of myocardial infarction in patients taking cyclo-oxygenase-2 inhibitorsor conventional non-steroidal anti-inflammatory drugs population based nested case-control analysis.. BMJ 2005 330 1366. 

Mamdani M, JuurlinkDN, Lee DSetal. Cyclo-oxygenase-2 inhibitors versus non-selective non-steroidal anti-inflammatory drugs and congestive heart failure outcomes in elderly patients a population-based cohort study. Lancet 2004 363 1751-1756. 

Munkittrick, D.R., M.E. McMaster, C.B. Portt, G.J. Van Der Kraak, I.R. Smith and D.G. Dixon. Changes in maturity, plasma sex steroid levels, hepatic mixed function oxygenase activity, and the presence of external lesions in lake whitefish (Coregonus clupeaformis) exposed to bleached Kraft mill effluent. Can. J. Fish Aquat. Sci. 49 1560-1569, 1992. 

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