Heme enzymes activity

Studies on the oxygen activation mechanisms by new heme enzymes using hemoprotein mutants and synthetic heme models 96YGK1046. 

Achieving fast electron transfer to enzyme active sites need not be complicated. As mentioned above, many redox enzymes incorporate a relay of electron transfer centers that facilitate fast electron transfer between the protein surface and the buried active site. These may be iron-sulfur clusters, heme porphyrin centers, or mononuclear... 

A marked interference with heme synthesis results in a reduction of the hemoglobin concentration in blood. Decreased hemoglobin production, coupled with an increase in erythrocyte destruction, results in a hypochromic, normocytic anemia with associated reticulocytosis. Decreased hemoglobin and anemia have been observed in lead workers and in children with prolonged exposure at higher PbB levels than those noted as threshold levels for inhibition or stimulation of enzyme activities involved in heme synthesis (EPA 1986a). 

Que, L. and R. Y. N. Ho (1996). Dioxygen activation by enzymes with mononuclear non-heme iron active sites. Chem. Rev. 96(7) 2607-2624. 

Soluble forms of guanylyl cyclase are activated by nitric oxide. These enzymes are homologous to the catalytic domains of the membrane-bound forms of GC. They are considered heterodimers because they appear to exist, under physiological conditions, as complexes of a and P subunits, each with Mr of 70-80 kDa. Both types of soluble GC contain three primary domains an amino-terminus heme domain responsible for binding nitric oxide (NO), a dimerization domain and a carboxy terminus catalytic domain. The aP heterodimer is required for enzyme activity [35]. This can be seen as similar to the situation for AC, which contains two catalytic entities within a single polypeptide chain (Fig. 21-5). 

Figure 9.1 CYP catalytic cycle. The sequential two-electron reduction of CYP and the various transient intermediates were first described in the late 1960s [206], The sequence of events that make up the CYP catalytic cycle is shown. The simplified CYP cycle begins with heme iron in the ferric state. In step (i), the substrate (R—H) binds to the enzyme, somewhere nearthe distal region of the heme group and disrupts the water lattice within the enzymes active site [207], The loss of water elicits a change in the heme iron spin state (from low spin to high spin) [208]. Step (ii) involves the transfers of an electron from NADPH via the accessory flavoprotein NADPH-CYP reductase, with the electron flow going from the reductase prosthetic group FAD to FMN to the CYP enzyme [206,209]. The...

Peroxidases (E.C. 1.11.1.7) are ubiquitously found in plants, microorganisms and animals. They are either named after their sources, for example, horseradish peroxidase and lacto- or myeloperoxidase, or akin to their substrates, such as cytochrome c, chloro- or lignin peroxidases. Most of the peroxidases studied so far are heme enzymes with ferric protoporphyrin IX (protoheme) as the prosthetic group (Fig. 1). However, the active centers of some peroxidases also contain selenium (glutathione peroxidase) [7], vanadium (bromoperoxidase)... 

Removal of calcium from HRP C has a significant effect not only on enzyme activity and thermal stability, but also on the environment of the heme group. The calcium-depleted enzyme has optical, EPR, and H NMR spectra that are different from those of the native enzyme (211). Temperature dependence studies indicate that the heme iron exists as a thermal admixture of high- and low-spin states. Kinetic measurements at pH 7 show that ki, the rate constant for compound I formation, is only reduced marginally from 1.6 0.1 x 10 to 1.4 x lO M s , whereas k, the rate constant for compound II reduction, is reduced from 8.1 1.6 x 10 to 3.6 x lO M s (reducing substrate p-aminobenzoic acid), 44% of its initial value (211). There can be little doubt that this is the main reason for the loss of enzyme activity on calcium removal. 

Once the oxy complex is formed, a second electron transfer to the HO heme effectively reduces the oxy complex to the peroxide level. From this point many heme enzymes catalyze the heterolytic fission of the peroxide 0-0 bond, leaving behind the well known oxyferryl center, (Fe-0) +, characteristic of peroxidase compound 1 and similar to the active hydroxylating intermediate thought to operate in P450s. However, in HO the active oxidizing intermediate is peroxide. Peracids that form the (Fe-0) + intermediate do not support the HO reaction, whereas H2O2 addition to Fe + HO does support substrate hydroxylation 187, 188). EPR and ENDOR spectroscopy have been used to analyze the cryo-genically reduced oxy-HO complex 189). In these studies reduction of... 

In cellular smdies indium exposure has been associated with a general suppression of protein synthesis and the induction of heme oxygenase, which in turn is associated with the reduction of enzyme activities dependent on cytochrome P-450. The significance of these alterations in the synthesis and maintenance of various enzyme systems in relation to a possible carcinogenic response has not been determined. ... 

Dawson, J. H. and Sono, M. (1987) Cytochrome P450 chloroperoxidase thiolate-ligand heme enzymes. Spectroscopic determination of their active site structure and mechanistic implication of thiolate ligation. Chem. Rev. 87, 1255-1276. 

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