Copper containing monooxygenase

Analogous side-chain oxidations occur in various biosynthetic pathways. The neurotransmitter norepinephrine, for instance, is biosynthesized from dopamine by a benzylic hydroxylation reaction. The process is catalyzed by the copper-containing enzyme dopamine /3-monooxygenase and occurs by a radical mechanism. A copper-oxygen species in the enzyme first abstracts the pro-R benzylic hydrogen to give a radical, and a hydroxyl is then transferred from copper to carbon. 

H. H. T. Nguyen, S. J. Elliott, J. H. K. Yip, S. I. Chan (1998) The particulate methane monooxygenase from Methylococcus capsulatus (Bath) is a novel copper-containing three-subunit enzyme - Isolation and characterization. J. Biol. Chem., 273 7957-7966... 

Lieberman, R. L. Shrestha, D. B. Doan, P. E. Hoffman, B. M. Stemmier, T. L. Rosenzweig, A. C. Purified particulate methane monooxygenase from Methylococcus capsulatus (Bath) is a dimer with both mononuclear copper and a copper-containing cluster. Proc. Natl. Acad. Sci. USA 2003, 100(1), 3820-3825. 

In light of the accepted mechanism for cytochrome P-450 (97-100), a superoxo-Cu(II) intermediate is further reduced, leading to dioxygen activation. Accordingly, a monomeric peroxo or hydroperoxo copper(II) complex serves as a synthetic model for these intermediates of copper-containing monooxygenases. However, no well-characterized complexes of these types are available to date. Formation of a monomeric hydroperoxo or acylperoxo complex was reported to occur when a trans-/u-l,2-peroxo complex, [(Cu(TPA))2(02)]z+, was treated with H+ or RC(O)+, but no details of the structures and properties of the complexes were provided (101). A related complex, a monomeric acylperoxo cop-per(II) complex, was synthesized (102). Low-temperature reaction of a dimeric copper(II) hydroxide complex, [Cu(HB(3,5-iPr2pz)3)]2(OH)2, with 2 equivalents of m-CPBA (3-chloroperoxybenzoic acid) yielded a monomeric acylperoxo complex whose structure was characterized by... 

In vivo tolerance to copper is quite high, however, deficiency and excess are serious problems. Infants are particularly vulnerable as they take time to assimilate the correct levels and it is known that trace copper from cooking utensils or water pipes can cause childhood cirrhosis. Copper deficiency leads to arterial weakness and heart enlargement. This is probably caused by a decrease in catecholamine neurotransmitters derived from the biosynthesis of adrenaline which requires the copper-containing enzymes phenylalanine hydroxylase, dopamine P-monooxygenase and tyrosinase. 

Central Nervous System. Dopamine monooxygenase (DMO) is an enzyme that requires copper, as a cofactor and uses ascorbate as an electron donor. This enzyme catalyzes the conversion of dopamine to norepinephrine, the important neurotransmitter. There are soluble and membrane-bound forms of the enzyme, the latter being found in the chromaffin granules of the adrenal cortex. Monoamine oxidase, one of the numerous amine oxidases, is a copper-containing enzyme that catalyzes the degradation of serotonin in the brain and is also involved in the metabolism of the catecholamines. 

Iron- and Copper-Containing Monooxygenases V. Ullrich and W. Duppel... 

Tyrosinases (synonyms phenol oxidases, poly-phenolases or polyphenol oxidases) are copper-containing monooxygenases, which catalyze two consecutive reactions with molecular oxygen as cosubstrate, namely the ortho-hydroxylation of phenols and the oxidation of the resulting catechols to ortho-quinones (Fig. 16.3-4). 

In addition to these three, there are also monooxygenase enzymes containing single nonheme iron or copper ions, or nonheme iron plus an organic cofactor such as a reduced pterin at their active sites.Just as with the dioxygenase enzymes, we do not know how similar the mechanisms of the different metal-containing monooxygenase enzymes are to one another. The enzyme for which we have the most information is cytochrome P-450, and we will therefore focus our discussion on that system. Speculations about the mechanisms for the other systems are discussed at the end of this section. 

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