Monooxygenases P450, methane monooxygenase

Some indication of active-site acidic functionality in P450 dioxygen scission can be revealed by the comparative evaluation of kinetic parameters in protonated and deuterated waters. The use of kinetic solvent isotope effects (KSIEs) has been valuable in the determination of potential proton-linked dioxygen activating enzymes such as P450 -, methane monooxygenase (MMO), ... 

Guallar, V., Gherman, B. F., Lippard, S.J. and Friesner, R. A. (2002) Quantum chemical studies of methane monooxygenase comparison with P450, Current Opinion in Chemical Biology 6, 236-242. 

Figure 3 Illustration of possible partial reaction cycles of some oxygenase enzymes. Water molecules and protein ligands have sometimes been omitted for clarity, (a) P450 (18) (b) intradiol dioxygenase (7) (c) lipoxygenase (7) (d) a-KG-dependent non-heme Iron enzymes (14) (e) soluble methane monooxygenase (15) (f) uncoupled blnuclear copper (16) (g) coupled blnuclear copper (h) flavin monooxygenases (17).

In addition to their role in kinetics, radical clocks also serve an important mechanistic function in that the formation of the rearranged product provides evidence for radical involvement in the first place. The incorporation of a ring-opening probe into the substrate, followed by product analysis—specifically, a search for rearranged product—has been used in mechanistic studies of the action of some enzymes, such as cyt P450 [61] and methane monooxygenase [62]. 

P.F. Hollenberg, D.A. K.opp et al. (2002). Evaluation of norcarane as a probe for radicals in cyto-chome P450-and soluble methane monooxygenase-catalyzed hydroxylation reactions. J. Am. Chem. Soc. 124, 6879-6886. 

Cytochrome P450 and soluble methane monooxygenase components and general enzyme characteristics... 

The value k n decreases for normal alkanes with increasing n. This effect reflects the growth of steric barriers as a result of the hydrophobic molecule rolling itself up into a coil . For n-octane, almost half the carbon atoms do not participate in the reaction. It should be noted that the rate constant of the oxidation remains practically unchanged despite the increase of the number of carbon atoms from pentane to octane. This may mean that only the C-H bonds of the primary and secondary carbon atoms from the hydrocarbon are reactive, i.e., ti)- and CO-1-carbon atoms. If this is so, then steric factors in the alkane oxidation by platinum complexes produce the same effect as they do in the selective oxidation under the action of monooxygenase with participation of cytochrome P450 and methane monooxygenase. 

Non-heme iron-containing monooxygenases, such as methane monooxygenase and o-hydroxylase, analogously to cytochrome P450, can transfer the oxygen atom from molecular oxygen to the C-H bonds of alkanes [24],... 

Fe(IV) is an important intermediate in such heme enzymes as cytochrome c oxidase and cytochrome P450, as well as the nonheme enzymes methane monooxygenase and ribonucleotide reductase. Voltammetric studies on yeast cytochrome... 

Biomimetic oxidation of cyclohexane was performed by Fish et al. in aqueous micelle system with t-butyl hydroperoxide (TBHP) and in the presence of biomimetic methane monooxygenase (MMO) enzyme complex [Fe20( 7-H20) ( )-OAc)L2] +. While in biphasic systems or in microemulsions, obtained by vigorous stirring, the reaction did not occur, the use of cetyltrimethylammonium hydrogensulfate (CTAHS) accelerated the reaction up to the rate observed in acetonitrile. Monti and collaborators developed another biomimetic system related to cytochrome P450, based on a porphyrin derivative, and successfully used it for the... 

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