Oxygen transfer hemes

The bottom line is that for substrates larger than one or two atoms in size, steric restrictions imposed on the peroxidase active site prevent oxygen transfer reactions and confine substrate-enzyme interactions to the heme edge. 

Figure 3.14. Kinetics of arg hydroxylation. In NADPH-driven reaction, shown step in the transfer of an electron from the reductase flavins (FMNH2) to the ferric heme. Oxygen then binds to form the Fe"02 speicie, which receives an electron from H4B to form a heme-peroxo intermediate. Subsequent steps that lead to Arg hydroxylation are rapid and genetate ferric iNOSoxy contaning NOHA and the H,B radical (Wei, et al., 2001). Reproduced with permission.

This catalytic asymmetric oxidation yielded J -methylphenylsulfoxide with a productivity of30g/l/day andane.e. >98% [35]. Chloroperoxidase is the most versatile peroxidase with better stability compared to other peroxidases, because spontaneous oxidation can be suppressed in the presence of ascorbic acid or dihydroxyfu-maric acid, and with better enantioselectivity because substrate access to the heme iron and ferryl oxygen favors stereoselective oxygen transfer [36]. Chloroperoxidase has been used for catalyzing the oxidation of cis-cydopropylmethanols with much higher enantioselectivity than trans-isomers [37]. 

G. Yin, M. Buchalova, A. M. Danby, C. M. Perkins, D. Kitko, J. D. Carter, W. M. Scheper, D. H. Busch, Olefin epoxidation by the hydrogen peroxide adduct of a novel non-heme manga-nese(IV) complex Demonstration of oxygen transfer by multiple mechanisms, Inorg. Chem. 45 (2006) 3467. 

Table 12. Various types of cytochrome c oxidase. The index 3 indicates a heme which transfers electrons directly to oxygen. A hyphen indicates the lack of the corresponding group. According to van der Oost et al. 1994 [279] ...

Whereas oxygen binding in humans and many other animals involves heme units, not all life-forms bind and carry dioxygen in this way. Hemerythrin is a nonheme iron protein used by sipunculid and brachiopod marine invertebrates for oxygen transfer and/or storage. 

The current understanding of oxygen activation by P-450 is summarized as follows (Scheme II) (Ic, 5a, b) (i) incorporation of a substrate to the resting ferric state (1) of the active site of the enzyme to afford the ES complex (2) (//) one-electron reduction of the heme from NAD(P)H via an associated reductase enzyme (Hi) reaction of the reduced heme (3) with O2 to form an oxy complex (4a, 4b) (iv) one-electron reduction of the oxy complex to yield a peroxo complex (5) (v) protonation (or possibly acylation) of the peroxo oxygen (vi) the formation of active species, the so-called oxenoid [FeO + (7)], by heterolytic 0-0 bond cleavage of (6) (v/7) oxygen transfer to the substrate. Thus, the overall stoichiometry can be expressed as in Eq. (2), where R is orR C(0) ... 

In discussing the reaction cycle of the cytochrome P450s, it is useful to incorporate similar states which appear to be more or less stable in other heme-oxygen systems. The sequential steps of oxygen activation are those that follow the formation of the ferrous reduced iron-porphyrin state that is generated by electron transfer from the physiological redox donor. These steps are formally ... 

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