Liver sulfite oxidase

One-electron reduction of chicken liver sulfite oxidase produces a species in which the molybdenum centre is Mo(V) and the b-type heme is low-spin Fe(III).90... 

The folding pattern of cytochrome b5 is also found in the complex heme protein flavocytochrome b2 from yeast (Chapter 15)133 and probably also in liver sulfite oxidase134,135 Both are 58-kDa peptides which can be cleaved by trypsin to 11-kDa fragments that have spectroscopic similarities and sequence homology with cytochrome b5. Sulfite oxidase also has a molybdenum center (Section H). The 100-residue N-terminal portion of flavocytochrome b2 has the cytochrome b5 folding pattern but the next 386 residues form an eight-stranded (a / P)8 barrel that binds a molecule of FMN.133,136 All of these proteins pass electrons to cytochrome c. In contrast, the folding of cytochrome... 

Two other families of molybdoenzymes are the sulfite oxidase family6463 13 and the dimethylsulfoxide reductase family.632 641 Nitrogenase (Chapter 24) constitutes a fourth family. Sulfite oxidase (Eq. 16-60) is an essential human liver enzyme (see also Chapter... 

The first hint of an essential role of molybdenum in metabolism came from the discovery that animals raised on a diet deficient in molybdenum had decreased liver xanthine oxidase activity. There is no evidence that xanthine oxidase is essential for all life, but a human genetic deficiency of sulfite oxidase or of its molybdopterin coenzyme can be lethal.646,646a,b The conversion of molybdate into the molybdopterin cofactor in E. coli depends upon at least five genes.677 In Drosophila the addition of the cyanolyzable sulfur (Eq. 16-64) is the final step in formation of xanthine dehydrogenase.678 It is of interest that sulfur (S°) can be transferred from rhodanese (see Eq. 24-45), or from a related mercaptopyruvate sulfurtransferase679 into the desulfo form of xanthine oxidase to generate an active enzyme.680... 

Protein sequence homology suggests that sulfite oxidase and assimilatory nitrate reductase are members of the same molybdenum enzyme subfamily [31]. Consistent with this classification, the cofactors of sulfite oxidase and assimilatory nitrate reductase differ significantly from those in dmso reductase, aldehyde oxido-reductase, xanthine oxidase (see Section IV.E.), and even respiratory nitrate reductase (Section IV.D). The EXAFS of both sulfite oxidase [132-136] and assimilatory nitrate reductase [131,137,138] and x-ray studies of sulfite oxidase (chicken liver) [116] confirm that the molybdenum center is coordinated by two sulfur atoms from a single MPT ligand and by the sulfur atom of a cysteine side chain. The Movl state is bis(oxido) coordinated (Figure 14). 

Sulfite Oxidase. This enzyme, isolated from bovine (26, 27) and chicken liver (28), catalyzes the oxidation of sulfite to sulfate. This is possibly a crucial function in animals as S032" (or S02, its gaseous precursor) is toxic while S042" is relatively innocuous. For example, one of the first signs of molybdenum deficiency in rats is a greatly increased susceptibility to S02 poisoning (28). In addition, a human child bom without sulfite oxidase activity did not survive for very long (29). 

The chlorides of the product can be substituted by other ligands and mono(-dithiolene) complexes [MoO(AdS)2(S2C2Me2)], [MoO(SR)2(bdt)l (R = Ad or 2,4,6-/-Pr3CeH2) and [MoOCl(SC6H2-2,4,6- -Pr3)(bdt)] have been synthesized and characterized (90). These complexes represent the first examples of five-coordinate monodithiolene MovO complexes each has a square-pyramidal structure with an apical oxogroup. Representatives of these MovO centers exhibit rhombic EPR spectra that show some similarities to signals exhibited by the low- and high-pH forms of chicken liver sulfite oxidase (91). 

Sulfite and bisulfite ions can be oxidized to form plasma protein S-sulfonates. Bisulfite is further detoxified by sulfite oxidase, which is found primarily in liver mitochondria (Gunnison et al. 1987) and is excreted as sulfate ion in the urine. Sulfite oxidase also has been detected in other tissues, including kidney and heart (Cabre et al. 1990). 

Sulfite oxidase concentrations vary in animals and humans, and the efficiency of sulfite oxidation depends primarily on sulfite oxidase activity (Gunnison and Palmes 1974). Cohen et al. (1973) observed sulfite oxidase activity to be lower in the livers of young versus mature rats, sulfite oxidase activity in 1-d-old rats was one-tenth that of adults. Decreased activity of sulfite oxidase in sulfite-oxidase-deficient rats resulted in higher in vivo concentrations of sulfite, whereas sulfite-oxidase-competent rats exposed to sulfur dioxide lacked sulfite in the plasma (Gunnison et al. 1987). 

FIGURE 6. The structure of chicken liver sulfite oxidase (from Kisker et al., 1997). The heme domain is shown at left, the molybdenum-binding portion of the protein at right. The redox-active centers are rendered in wireframe representation. 

Brody, M. S., and Hille, R., 1995, The reaction of chicken liver sulfite oxidase with dimethyl-sulfite, Biochim. Biophys. Acta. 1253 133iil35. 

Sulfite Oxidase Family Sulfite oxidase Chicken liver 2, 106 Mo02(SCys)(MPT) 65-heme S03 " — S04 " ISOX... 

Figure 3 Active site of chicken liver sulfite oxidase. The apical group is a terminal 0x0 ligand, the second oxygen is an 0x0 ligand in the oxidized enzyme...

The postulated catalytic cycles for pterin-containing molybdenum enzymes involve a two-electron change at the molybdenum atom (Mo(VI) Mo(IV)). Microcoulometric titrations of nitrate reductase Chlorella vulgaris) (76), milk xanthine oxidase (77), and sulfite oxidase (78) show that their molybdenum centers are reduced by two electrons. The reduction potentials for the molybdenum center of chicken liver sulfite oxidase are strongly dependent upon pH and upon anion concentration (78). 

D DIGE MS Compound A Rat liver Chemical liver steatosis study T Acetyl CoA pathway enzymes 4- sulfite oxidase... 

Kessler DL, Rajagopalan KV (1972) Purification and properties of sulfite oxidase from chicken liver. J Biol Chem 247 6566-6573... 

Sulfite oxidase bovine liver, chicken liver, r ... 

Sulfite oxidase is a molybdoenzyme which catalyzes the conversion of sulfite derived from cysteine, methionine and related compounds to inorganic sulfate. Sulfite oxidase has been isolated from bovine, chicken, rat, and human liver. It is located in the intermembrane space of mitochondria, and its physiological electron acceptor is mitochondrial cytochrome c. The purified enzymes consist of two identical subunits with a molecular weight range of 55-60 kDa, containing each one atom Mo and one cytochrome b5-type heme. 

Garrett RM, Bellissimo DB and Rajagopaian KV (1995) Molecular cloning of human liver sulfite oxidase. Biochim Biophys Acta 1262 147-149. 

Garrett RM and Rajagopaian KV (1984) Molecular cloning of rat liver sulfite oxidase. Expression of a eukaryotic Mo-pterin-containing enzyme in Escherichia coli. J Biol Chem 269 272 - 276. 

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