Cytochrome iron metabolism

Iron metabolism cytochrome c oxidase oxidation of cytochrome c... 

Fig. 1. Schematic overview of copper trafficking and homeostasis inside the yeast cell. The actions of Mad and Ace 1, copper-dependent metalloregulatory transcription factors, control the production of copper import [copper transporter (Ctr) and reductase (Fre)] and detoxification/sequestration [metallothionein (MT)] machineries, respectively. Three chaperone-mediated delivery pathways are shown. Atxl shuttles Cu(I) to the secretory pathway P-type ATPase Ccc2 (right). CCS delivers Cu(I) to the cytoplasmic enzyme copper-zinc superoxide dismutase (SOD) (left). Coxl7 shuttles Cu(I) to cytochrome c oxidase (CCO) in the mitochondria (bottom). Mitochondrial proteins Scol and Sco2 may also play a role in copper delivery to the CuA and CuB sites of CCO. Copper metabolism and iron metabolism are linked through the actions of Fet3, a copper-containing ferroxidase required to bring iron into the cell (lower right) (see text).

RNA secondary structure plays a role in the regulation of iron metabolism in eukaryotes. Iron is an essential nutrient, required for the synthesis of hemoglobin, cytochromes, and many other proteins. However, excess iron can be quite harmful because, untamed by a suitable protein environment, iron can initiate a range of free-radical reactions that damage proteins, lipids, and nucleic acids. Animals have evolved sophisticated systems for the accumulation of iron in times of scarcity and for the safe storage of excess iron for later use. Key proteins include transferrin, a transport protein that carries iron in the serum, transferrin receptor, a membrane protein that binds iron-loaded transferrin and initiates its entry into cells, and ferritin, an impressively efficient iron-storage protein found primarily in the liver and kidneys. Twenty-four ferritin polypeptides form a nearly spherical shell that encloses as many as 2400 iron atoms, a ratio of one iron atom per amino acid (Figure 31.37). 

One striking similarity between iron metabolism in animals and bacteria is that both contain ferritin (63). Bacterial ferritin, or bacfer, resembles ferritin in a number of respects (Section IV), but a key difference is that bacfer is also a 6-type cytochrome (129), cytochrome bi (126). Thus the question arises Is it primarily a cytochrome or primarily an iron storage protein This question opens up a large number of avenues of research, some of which are described in Section IV, that we believe will help define further how animal ferritin functions. One important area is that of genetic control of bacfer expression. 

The two metal ions also function in concert in proteins such as cytochrome oxidase, which catalyzes the transfer of four electrons to dioxygen to form water during respiration. Whether any types of biological reactions are unique to copper proteins is not clear. However, use of stored iron is reduced by copper deficiency, which suggests that iron metabolism may depend on copper proteins. 

Fig. 44.6. Iron metabolism. Iron is absorbed from the diet, transported in the blood in transferrin, stored in ferritin, and used for the synthesis of cytochromes, iron-containing enzymes, hemoglobin, and myoglobin. It is lost from the body with bleeding and sloughed-off cells, sweat, urine, and feces. Hemosiderin is the protein in which excess iron is stored. Small amounts of ferritin enter the blood and can be used to measure the adequacy of iron stores. RE = reticuloendothelial.

Cyt c has an important role in the production of ATP in the mitochondrial respiratory electron-transfer chain, cyt c transfers electrons from the transmembrane cyt bc complex to cytochrome c oxidase." " Cyt c also delivers electrons to cytochrome c peroxidase, which facilitates the reduction of hydrogen peroxide to water. In addition to its life-sustaining electron-transfer functions, cyt c is required for activation of the cell-death protease, caspase-3, in apoptosis." " Defects in cyt c biogensis have been implicated in pathogenic responses related to copper and iron metabolism, and prokaryotic heme biosynthesis. ... 

Ceruloplasmin (Cp), secreted into the blood stream, appears to be ubiquitous in vertebrates. There is extensive in vitro evidence that Cp efficiently catalyzes the oxidation of Fe to Fe under near physiological conditions. The role of Cp in iron metabolism is widely accepted and there is strong evidence for a secondary role in copper transport/regulation. Defects in hepatic biosynthesis of Cp may result in diseases such as Wilson s disease. There is conclusive evidence that Cp is the source for the copper found in cytochrome c oxidase and CuZn-SOD in cells. Cp inhibition of Fenton chemistry-induced oxidative damage of deoxyribose, lipids, and DNA points to an antioxidant role, which would explain the increase in Cp concentration in response to acute infection or inflammation. 

Low et al. (2004) have proposed a model to explain thioacetamide-induced hepatotox-icity and cirrhosis in rat livers. The pathways of thioacetamide-induced liver fibrosis were found to be initiated by thioacetamide S-oxide derived from the biotransformation of thioacetamide by the microsomal flavin-adenine nucleotide containing monooxygenase and cytochrome P450 systems and involve oxidative stress and depletion of succinyl-CoA, thus affecting heme and iron metabolism. Karabay et al. (2005) observed such hepatic damage in rats with elevation of total nitrite level in livers and decrease in arginase activity. The authors have reported that nitrosative stress was essentially the critical factor in thioacetamide-induced hepatic failure in rats. 

Hemoproteins are also involved in gene regulation, iron metabolism (cytochrome P450), drug metabolism, and hormone synthesis. Truly, where there is life there are porph)nlns. 

The iron-heme complex is present in another class of proteins called the cytochromes. Here too, the iron forms an octahedral complex, but both the fifth and sixth ligands are part of the protein structure [Figure 20.20(c)]. Because the ligands are firmly bound to the metal ion, they cannot be displaced by oxygen or other ligands. Instead, the cytochromes act as election carriers, which are essential to metabolic processes. In cytochromes, iron undetgoes rapid reversible redox processes ... 

FePc is a model for iron porphyrins, which are of central importance in binding oxygen to hemoglobin in blood, and as prosthetic groups in cytochromes. Iron porphyrins have been proposed as mediators in bio-dehalogenation27 and in metabolic activation of toxic chemicals in humans . By a related process, reduction of alkyl vicinal dibromides to alkenes can be accomplished by generating the Co(I) form of the macro-cyclic vitamin B12 complex at an electrode. The electrode serves a function similar to a redox enzyme by cycling Co(II) to Co(I). Such reactions are also catalyzed by CoPc and FePc. 

Cytochromes and Iron Sulfur Proteins in Bacterial Sulfur Metabolism (U. 

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