Hemoprotein

Hemoproteins bound to the protein surface consist of iron-containing porphyrinic chromophores. By varying the oxidation state of the iron atom, these proteins participate in various biological reactions involving oxygen 

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HEMOPROTEINS. These proteins are actually a subclass of metalloproteins because their prosthetic group is heme, the name given to iron protoporphyrin IX (Figure 5.15). Because heme-containing proteins enjoy so many prominent biological functions, they are considered a class by themselves. 

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

The Specific Reactions of Iron in Some Hemoproteins Philip George... 

Heme (C34H3204N4Fe) represents an iron-porphyrin complex that has a protoporphyrin nucleus. Many important proteins contain heme as a prosthetic group. Hemoglobin is the quantitatively most important hemoprotein. Others are cytochromes (present in the mitochondria and the endoplasmic reticulum), catalase and peroxidase (that react with hydrogen peroxide), soluble guanylyl cyclase (that converts guanosine triphosphate, GTP, to the signaling molecule 3, 5 -cyclic GMP) and NO synthases. 

Cytochrome P450 (CYP) mono-oxygenases, also called mixed function oxidases, are versatile hemoprotein enzymes that catalyze the cleavage of molecular oxygen to incoiporate one oxygen atom into a substrate molecule and one atom into water [1]. The general stoichiometry of the reaction is as follows (S-H, substrate) ... 

Activation of oxygen by cytochrome P-450 and other hemoproteins. D. I. Metelitsa, Russ. Chem. Rev. (Engl. Transl), 1982, 51,1042-1059 (184). 

Spin state/stereochemical relationships in iron porphyrins implications for the hemoproteins. W. R. Scheidt and C. A. Reed, Chem. Rev., 1981, 81, 543-555 (111). 

Hemoglobin, nitrosyl-, 4, 1194 Hemoglobin, oxy-diamagnetism, 6,686 Hemoproteins, 4,259 dioxygen... 

Woolley RG (1982) Natural Optical Acitivity and the Molecular Hypothesis. 52 1-35 Wiithrich K (1970) Structural Studies of Hemes and Hemoproteins by Nuclear Magnetic Resonance Spectroscopy. 8 53-121... 

Rieske JS. 1967. The quantitative determination of mitochondrial hemoproteins. Methods Enzymol 10 448-493. 

The cytochromes are iron-containing hemoproteins in which the iron atom oscillates between Fe + and Fe + during oxidation and reduction. Except for cytochrome oxidase (previously described), they are classified as dehydrogenases. In the respiratory chain, they are involved as carriers of electrons from flavoproteins on the one hand to cytochrome oxidase on the other (Figure 12-4). Several identifiable cytochromes occur in the respiratory chain, ie, cytochromes b, Cp c, a, and (cytochrome oxidase). Cytochromes are also found in other locations, eg, the endoplasmic reticulum (cytochromes P450 and h, and in plant cells, bacteria, and yeasts. 

Catalase is a hemoprotein containing four heme groups. In addition to possessing peroxidase activity, it is able to use one molecule of H2O2 as a substrate electron donor and another molecule of H2O2 as an oxidant or electron acceptor. 

Knowledge of the biochemistry of the porphyrins and of heme is basic to understanding the varied functions of hemoproteins (see below) in the body. The porphyrias are a group of diseases caused by abnormalities in the pathway of biosynthesis of the various porphyrins. Although porphyrias are not very prevalent, physicians must be aware of them. A much more prevalent clinical condition is jaundice, due to elevation of bilirubin in the plasma. This elevation is due to overproduction of bilirubin or to failure of its excretion and is seen in numerous diseases ranging from hemolytic anemias to viral hepatitis and to cancer of the pancreas. 

Proteins that contain heme (hemoproteins) are widely distributed in nature. Examples of their importance in humans and animals are listed in Table 32-1. 

Table 32-1. Examples of some important human and animal hemoproteins. ...

Many drugs when administered to humans can result in a marked increase in ALASl. Most of these drugs are metabolized by a system in the liver that utilizes a specific hemoprotein, cytochrome P450 (see Chapter 53). During their metabolism, the utilization of heme by cytochrome P450 is greatly increased, which in turn diminishes the intracellular heme concentration. This latter event effects a derepression of ALASl with a corresponding increased rate of heme synthesis to meet the needs of the cells. 

Hemoproteins, such as hemoglobin and the cytochromes, contain heme. Heme is an iron-porphyrin compound (Fe -protoporphyrin IX) in... 

All cytochrome P450s are hemoproteins and generally have a wide substrate specificity, acting on many exogenous and endogenous substrates. They represent the most versatile biocatalyst known. 

Hemoproteins which engage in electron transport — the cytochromes — are much more widely dispersed among living species and occur in microorganisms, plants and animals (13). Again there are two types of iron proteins which can perform the task of electron transport, the heme and the non-heme. The latter term has become practically synonymous... 

Fig. 3 illustrates schematically the structures of some well characterized hemoproteins. In the cytochrome series the desired range of redox potentials is achieved by variations in the axial ligands, contributed by the porphyrin moiety, as well as by substitutions around the periphery of the tetrapyrrole nucleus with groups of differing electron-attracting ability. 

Fig. 3. Schematic illustration of the iron linked groups in hemoproteins. The porphyrin ring containing the four pyrrole nitrogen atoms is shown as an elipsoid. The iron atom is 0.5 A out of the prophyrin plane in the direction of X (54). The axial ligands confirmed by crystallography (55, 56) are ...

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