Cytochrome nature

J-C Marchon, T Mashiko, CA Reed. How does nature control cytochrome redox potentials In C Ho, ed. Electron Transport and Oxygen Utilization. New York Elsevier North-Holland, 1982, pp 67-72. 

Iwata, S., Ostermeier, C., Ludwig, B., Michel, H. Structure at 2.8 A resolution of cytochrome c oxidase from Paracoccus denitrificans. Nature 376 660-669, 1995. 

Why has nature chosen this rather convoluted path for electrons in Complex 111 First of all. Complex 111 takes up two protons on the matrix side of the inner membrane and releases four protons on the cytoplasmic side for each pair of electrons that passes through the Q cycle. The apparent imbalance of two protons in ior four protons out is offset by proton translocations in Complex rV, the cytochrome oxidase complex. The other significant feature of this mechanism is that it offers a convenient way for a two-electron carrier, UQHg, to interact with the bj and bfj hemes, the Rieske protein Fe-S cluster, and cytochrome C, all of which are one-electron carriers. 

Cytochrome P450 enzymes have been the subject of a number of recent reviews in which their mechanism and scope of action are covered in much detail [1, 6, 10, 11]. The reader is referred to these articles for a more thorough account of the mechanism and reactivity of cytochrome P450 enzymes, while we present a few representative examples of cytochrome P450-catalyzed epoxidation below. The enzymes we chose are all involved in the biosynthesis of polyketide natural products. Polyketides are a large, structurally diverse family of compounds and have provided a wealth of therapeutically useful drugs and drug leads. 

Atovaquone, a hydroxynaphthoquinone, selectively inhibits the respiratory chain of protozoan mitochondria at the cytochrome bcl complex (complex III) by mimicking the natural substrate, ubiquinone. Inhibition of cytochrome bcl disrupts the mitochondrial electron transfer chain and leads to a breakdown of the mitochondrial membrane potential. Atovaquone is effective against all parasite stages in humans, including the liver stages. 

Henry M, Jolivet JP, Livage J (1991) Aqueous Chemistry of Metal Cations Hydrolysis, Condensation and Complexation. 77 153-206 Hider RC (1984) Siderophores Mediated Absorption of Iron. 57 25-88 Hill HAO, Rdder A, Williams RJP (1970) The Chemical Nature and Reactivity of Cytochrome P-450. 8 123-151... 

Williams PA, Cosme J, Ward A, Angove HC, Matak Vinkovic D, Jhoti H. Crystal structure of human cytochrome P450 2C9 with bound warfarin. Nature 2003 424 464-8. 

Cytochrome c is a heme containing protein which occurs in muscle at lower concentrations than does myoglobin. It was demonstrated some time ago (18) that oxidized cytochrome c reacts with gaseous nitrite oxide to produce a nltrosyl compound. Recent work (19, 20, 21) has examined the reactions of cytochrome c with nitrite and the contribution of the product formed to cured meat color in considerably more detail. The general conclusion is that even at the pH normally encountered in meat, the reaction can take place in the presence of ascorbic acid but probably does not affect meat color because of the unstable nature of the reaction product and the low concentration. 

In some cases, small biological redox partner proteins such as heme-containing cytochromes, ferredoxins comprising an iron-sulfur cluster, or azurin with a mononuclear Cu site have been used as natural mediators to facilitate fast electron exchange with enzymes. A specific surface site on the redox protein often complements a region on the enzyme surface, and enables selective docking with a short electron tunneling... 

Biomimetic studies typically have one or more of the following objectives (i) to reproduce in a small synthetic molecule reactivity that was theretofore only observed in an enzyme (ii) to understand the mechanisms of an enzymatic reaction and the relationship between the stereoelectronic attributes of the catalytic site and its reactivity and (iii) to develop practical catalysts by exploiting and adopting solutions that evolved in Nature. Biomimetic studies of cytochrome c oxidase have been particularly impactfull in addressing aim (ii). On the other hand, this approach is... 

In the natural environment of water and air, biological oxygenations of organic compounds are catalyzed by cytochrome P-450. One of the... 

Hereditary methemoglobinemia is classified into three types a red blood cell type (type I), a generalized type (type II), and a blood cell type (type HI). Enzyme deficiency of type I is limited to red blood cells, and these patients show only the diffuse, persistent, slate-gray cyanosis not associated with cardiac or pulmonary disease. In type II, the enzyme deficiency occurs in all cells, and patients of this type have a severe neurological disorder with mental retardation that predisposes them to early death. Patients with type III show symptoms similar to those of patients with type I. The precise nature of type III is not clear, but decreased enzyme activity is observed in all cells (M9). It is considered that uncomplicated hereditary methemoglobinemia without neurological involvement arises from a defect limited to the soluble cytochrome b5 reductase and that a combined deficiency of both the cytosolic and the microsomal cytochrome b5 reductase occurs in subjects with mental retardation. Up to now, three missense mutations in type I and three missense mutations, two nonsense mutations, two in-frame 3-bp deletions, and one splicing mutation in type n have been identified (M3, M8, M31). 

IL-1 (17.5) Monocyte/macrophage, lymphocyte, neutrophil, endothelium, fibroblast keratinocyte Activation of T cells, B cells, natural killer cells, osteoblasts, and endothelium. Induces fever, sleep, anorexia, ACTH release, hepatic acute phase protein synthesis and HSPs. Leads to myocardial depression, hypercoagulability, hypotension/sbock, and death. Simulates production of TNF, IL-6, and IL-8 and stress hormone release. Suppression of cytochrome P-450, thyro-globulin, and lipoprotein synthesis. Procoagulant activity. Antiviral activity. 

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