Sulfur Cluster Formation

Numerous Fe/S proteins are known in each of the three kingdoms of living organisms, i.e., in Eubacteria, Archaebacteria, and Eukaryotes, and their multiple functions in electron transport and catalysis are reviewed in Chapter 13. In contrast to most other cofactors, Fe/S clusters are essentially inorganic in nature, consisting simply 

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Although iron-sulfur proteins are found in various cellular localizations in eukaryotic cells, mitochondria are the major site of Fe-S cluster biosynthesis (Lill et ah, 1999). Deletions in nuclear genes involved in mitochondrial iron-sulfur cluster formation lead to massive accumulation of iron in mitochondria (Chapter 7). For example, deletion of ATM1, a mitochondrial ATPase, which seems to be responsible for the export of Fe-S clusters, leads to respiratory incompetence, excessive iron accumulation and leucine auxotrophy (Kispal et ah, 1999). In Ayfhl cells there is only partial loss of mitochondrial Fe-S enzymes and the cells are not leucine auxotrophs. 

Inspection of the citrate structure shows a total of four chemically equivalent hydrogens, but only one of these—the pro-/J H atom of the pro-i arm of citrate—is abstracted by aeonitase, which is quite stereospecific. Formation of the double bond of aconitate following proton abstraction requires departure of hydroxide ion from the C-3 position. Hydroxide is a relatively poor leaving group, and its departure is facilitated in the aeonitase reaction by coordination with an iron atom in an iron-sulfur cluster. 

The mimicking of the iron-sulfur clusters by synthetic chemistry has been quite successful over the years. One of the last synthetic clusters to be obtained was the [3Fe-4S] cluster (109, 110). This new synthetic compound was useful for the demonstration of interconversion pathways, as well as for the formation of different heterometal clusters beyond those produced in proteins (111). The [3Fe-4S] core... 

Tetranuclear iron-sulfur clusters of the type [Fe4S4(SR)4]2, where R = CH2C6H5 and C6H5, were found138 to catalyze the reduction of C02 in DMF solutions. Controlled-potential electrolyses were carried out in a C02-saturated 0.1 M tetrabutylammonium tetrafluoroborate (TBAT)-DMF solution at a mercury pool cathode. In the absence of a catalyst, C02 was substantially reduced only at potentials more negative than -2.4 V versus SCE, while in the presence of a cluster, the reduction took place at around -1.7 V thus, potential shift of ca. 0.7 V was achieved. The products were analyzed by means of gas chromatography and isotachophoresis. Without a catalyst, oxalate was the main product, and addition of small amounts of water to the DMF solution favored formate production, whereas in the presence of the catalyst, formate was produced predominantly even in a dry DMF solution. This result was interpreted in terms of indirect reduction of C02, proceeding by electron transfer from the reduced cluster to C02 in the bulk... 

Some metal-sulfur clusters have been used in anhydrous organic solvents as C02 electrocatalysts. They lead mainly to HCOO-,183-185 except when LiBF4 is used as electrolyte, where oxalate formation is observed.186,187... 

As previously mentioned, past studies used non-filtered air with unknown concentrations of trace gases at unknown relative humidities. Also, many of the studies used plastic aging chambers that may have introduced volatile monomers into the air. These unknown factors are important to determine in order to fully understand the nature of the ultrafine particle mode. According to the classical thermodynamic theory of ion cluster formation (Coghlan and Scott, 1983), the relative humidity and trace gases will affect the existence of condensation nuclei. Megaw and Wiffen (1961) observed an increase in nuclei formation with the presence of sulfur dioxide. 

NO formation, although this reaction occurred under aerobic conditions and was also observed with NOj (Stuehr and Nathan, 1989). It is important to point out, however, that individual iron-sulfur clusters do not exhibit uniform sensitivity to NO reaction, and inhibition of enzymatic activity can occur in either the absence or presence of the appearance of the g = 2.04 DNIC signal (Hyman and Arp, 1988 Hyman et al., 1992). It is thus unclear whether the loss of iron enzyme function is due to NO or oxidation products. 

Vanin et al. (1992) have performed a careful EPR study of the treatment of cells from a cultured macrophage line with NO. A 5-min treatment of these cells with low (—20 juM) NO results in the appearance of DNIC signals, but without concomitant decrease in the intensities of the signals from mitochondrial iron-sulfur clusters. These results indicate that under at least some conditions DNIC formation occurs with iron which is not part of the mitochondrial electron transfer chain, as suggested by Drapier et al., (1992) and Bergonia and co-workers... 

Salerno, J. C., Ohnishi, T., Lim, J., and King, T. E. (1976). Tetranuclear and binuclear iron-sulfur clusters in succinate dehydrogenase A method of iron quantitation by formation of paramagnetic complexes. Biochem. Biophys. Res. Commun. 73, 833-839. 

Suspension of the metal oxide (CuO, CofOH)2, 552 or Ni(OH)2) in a mixture of ethylene glycol, aniline, and sulfuric acid led to simultaneous metal cluster formation and polymerization... 

Johnson D, Dean D (2004) Structure, function, and formation of biological iron-sulfur clusters. Annu Rev Biochem 74 247-281... 

The current model for FeS cluster formation is based mainly on studies of Saccharomyces and human cells (reviewed in bill and Muhlenhoff 2006 Rouault and Tong 2005 Tachezy and Dolezal 2007). The pyridoxal phosphate-dependent cysteine desulfurase (IscS) is a central component catalyzing the production of sulfur from -cysteine (Ii et al. 1999 Schwartz et al. 2000). The released sulfur is transferred to IscU which constitutes a scaffold for the formation of a transient FeS cluster (Agar et al. 2000). Subsequently, the FeS cluster is transferred to mitochondrial apoproteins with the assistance of the... 

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