Human sulfite oxidase

K. V. In vitro incorporation of nascent molybdenum cofactor into human sulfite oxidase, J Biol Chem 2001, 276, 1837-1844. 

Garrett, R. M., Johnson, J. M., Graf, T. N., Feigenbaum, A., and Rajagopalan, K.V., 1998, Human sulfite oxidase R160Q identification of the mutation in a sulfite oxidase-deficient patient and expression and characterization of the mutant enzyme, Proc. Natl. Acad. Sci. (USA) 95 6394116398. 

This family includes the sulfite oxidases and dehydrogenases of prokaryotes Thiobacilli sp.), plants, birds, and animals, and the assimilatory nitrate reductases from bacteria, algae, fungi, and plants. The sulfite oxidases of higher eukaryotes are 100-110kDa homodimers (Table 1) they are located in the mitochrondrial intermembrane space and catalyze the oxidation of toxic sulfite to innocuous sulfate (equation 7). Human sulfite oxidase deficiency leads to major neurological abnormalities, mental retardation, dislocation of the ocular lenses, and early death. ... 

The importance of the functional layer on an electrode to the interaction of an enzyme with the surface is brought out by Kudelski s studies with Cu-containing tyrosinase (a phenol oxidase) [305] and laccase [306]. Using w-functionalized thiols he showed that electron transfer was not prevented between the electrode and the enzyme. That the local environment of the enzyme is important has also been demonstrated in a recent study of human sulfite oxidase using SERRS and cychc... 

Millo, D., Leimkuehler, S., Mroginski, M.A., Wollenberger, U., Hildebrandt, P., and Weidinger, LM. (2010) Redox properties and catalytic activity of surface-bound human sulfite oxidase smdied by a combined surface enhanced... 

Enzymes of the sulfite oxidase family, such as human sulfite oxidase, plant nitrate reductase, or the E. coli YedY protein (sulfite oxidase homologue) bind the MPT form of Moco (54) without further modification. So far, YedY represents the only molybdoenzyme isolated from E. coli that is characterized by the presence of the MPT... 

Johnson JL, Jones HP and Rajagopaian KV (1977) In vitro reconstitution of demolybdosulfite oxidase by a molybdenum cofactor from rat liver and other sources. J Biol Chem 252 4994-5003. Johnson JL and Rajagopaian KV (1976) Human sulfite oxidase deficiency. Characterization of the molecular defect in a multicomponent system. J Clin Invest 58 551-556. 

Figure 4.11 MCA spectra from a single element of a Ge array detector showing the effects of including a Zr filter and Soller slit assembly. For the without filter data, the intensity of the incident beam was attenuated by approximately a factor of 20 by inserting an aluminum metal absorber into the upstream beam in order to maintain the detector at a non-saturating count-rate. The sample was an aqueous solution of human sulfite oxidase (0.2 mM Mo, 20 mM PIPES pH 7.0). The incident X-ray energy was 20900 eV, equivalent to the elastic scatter energy.

XAS and EPR redox titration of the Cys207— Ser mutant human sulfite oxidase. The Mo(v) EPR signal intensity is zero on the reductive half of the titration (open points) and climbs to 100% Mo(v) on the oxidative half-titration (filled points). The EXAFS Fourier transforms (Mo-S phase-corrected) of redox-poised samples are shown adjacent to the potentials above the redox titration and the structures derived from curve-fitting of the different oxidation states are shown above the transforms. The figure used the data of George et alf° replotted. 

Molybdenum is considered an ultra-trace element with an approximate amount of 5 mg in the adult human body. It is a cofactor for at least three enzymes in humans (sulfite oxidase, xanthine oxidase, and aldehyde oxidase) and is involved in the catabolism of sulfur-containing amino acids, purine, and pyrimidine. A better understanding of human molybdenum metabolism is needed in order to give evidence-based recommendations regarding optimal nutrition, although molybdenum deficiency and associated pathological symptoms have not yet been observed in humans [74]. 

Spricigo R, Dronov R, Lisdat F, Leimkuhler S, Scheller FW, Wollenberger U (2009) Electrocatalytic sulfite biosensor with human sulfite oxidase co-immobilized with cytochrome c in a polyelectrolyte-containing multilayer. Anal Bioanal Chem 393 225-233... 

Deficiency or Toxicity in Humans. Molybdenum deficiency in humans results in deranged metaboHsm of sulfur and purines and symptoms of mental disturbances (130). Toxic levels produce elevated uric acid in blood, gout, anemia, and growth depression. Faulty utiH2ation results in sulfite oxidase deficiency, a lethal inborn error. 

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... 

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). 

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). 

In humans, age-related differences have been observed in metabolism of sulfite to sulfate and in formation of sulfur trioxide (Constantin et al. 1996). Constantin et al. (1996) measured sulfur trioxide radicals and sulfite oxidase activity in polymorphonuclear leukocytes (PMNs) from four groups young adults (average age 25), older adults (average age 65), 3 centenarians (older than 100), and Down syndrome patients. They found significantly increased amounts of sulfur trioxide radicals in PMNs from healthy adults who had low sulfite oxidase activity. In centenarians and Down syndrome patients, generation of the sulfur trioxide radical was the primary mechanism for detoxification of sulfite. There was no correlation between the sulfur trioxide radical and sulfite oxidase activity. 

Three human redox enzymes, and a variety of bacterial enzymes, contain molybdenum chelated by two sulfur atoms in a modified pterin molybdopterin (see Figure 10.1). In sulfite oxidase, the other two chelation sites of the molybdenum are occupied by oxygen in xanthine oxidase / dehydrogenase (Section 7.3.7) and aldehyde oxidase, one site is occupied by oxygen and one by sulfur. In some bacterial enzymes, molybdopterin occurs as a guanine dinucleotide rather than free. In others, tungsten rather than molybdopterin is the chelated metal there is no evidence that any mammalian enzymes contain tungsten. 

Several important mammalian enzymes, such as sulfite oxidase, xanthine dehydrogenase, and aldehyde oxidase, require molybdenum as a cofactor. This organic component is a molybdopterin complex.Sulfite oxidase is probably the most important enzyme in relation to human health. This enzyme catalyzes the last step in the degradation of sulfur amino acids, oxidizing sulfite to sulfate and transferring electrons to cytochrome c. Xanthine dehydrogenase and aldehyde oxidase hydroxylate a number of heterocyclic substances, such as purines, pteridines, and others. ... 

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