Disease relevance of SUOX

• Molybdenum cofactor deficiency and isolated sulfite oxidase deficiency are autosomal recessive inborn errors of metabolism with severe neurological symptoms resulting from a lack of sulfite oxidase activity [1].
• MPT-free human sulfite oxidase apoprotein was obtained by heterologous expression in an Escherichia coli mutant with a defect in the early steps of MPT biosynthesis [2].
• Cerebral atrophy and cystic encephalomalacia were observed with neuroradiologic imaging and were noted in all 3 postmortem reports of isolated sulfite oxidase deficiency [3].
• We report a case of a newborn infant boy with isolated sulfite oxidase deficiency who presented with generalized seizures on his fourth day of life [3].
• Sulfite oxidase deficiency is characterized by severe neurologic dysfunction, dislocation of the lenses, and the accumulation and excretion of inorganic sulfite, thiosulfate, and S-sulfocysteine [4].

Psychiatry related information on SUOX

• Isolated sulfite oxidase deficiency is a rare autosomal recessive disease, characterized by severe neurological abnormalities, seizures, mental retardation, and dislocation of the ocular lenses, that often leads to death in infancy [5].

High impact information on SUOX

• The premier discoveries to emanate from my laboratory have been the sulfite oxidase, the several superoxide dismutases, the manganese catalase, and the catalase/peroxidase [6].
• Sulfite oxidase activity in skin fibroblasts average 1.07 nmol of cytochrome d reduced per milligram of protein per minute in control lines; it was not detectable (less than 5 per cent) in the patient [7].
• Molybdenum cofactor deficiency is a devastating disease with affected patients displaying the symptoms of a combined deficiency of sulfite oxidase and xanthine dehydrogenase [8].
• Use of conditioned media indicated that a relatively stable, diffusible precursor produced by group B cells could be used to repair sulfite oxidase in group A recipient cells [8].
• The ability of the patient's liver to synthesize the specific molybdenum cofactor required for activation of de-molybdo sulfite oxidase also appears to have been unimpaired [9].

Chemical compound and disease context of SUOX

• Human sulfite oxidase expressed in E. coli moeA(-) could be activated in vitro in the presence of MoeA and low concentrations of molybdate [10].
• Thiobacillus novellus shows a maximum induction of sulfite oxidase activity and a maximum growth rate as a result of supplementing the autotrophic growth medium with 4.0 microM ammonium molybdate [11].
• Therefore, the present study used SOX deficient rats since they are a more appropriate model for studying sulfite toxicity [12].
• To the contrary, sulfite oxidase deficiency is known in man, bisulfite is mutagenic for several test organisms, and the atmospheric SO2 level is positively correlated with death rates for several chronic diseases among some human populations [13].

Biological context of SUOX

• Point mutations were found in two alleles of the sulphite oxidase (SUOX) gene [14].
• Sulfite oxidase contains three domains: an N-terminal cytochrome b(5) domain, a central domain harboring the molybdenum cofactor (Moco) and a C-terminal dimerization domain [15].
• The resultant severe phenotype, which includes progressive neurological damage leading in most cases to early childhood death, results primarily from the deficiency of sulfite oxidase [16].
• To do so, we designed oligonucleotide primers for amplification of the predicted exons and intron-exon boundaries of the SUOX gene obtained from the completed draft version of the human genome [5].
• The mutation in the sulfite oxidase gene responsible for sulfite oxidase deficiency in a 5-year-old girl was identified by sequence analysis of cDNA obtained from fibroblast mRNA to be a guanine to adenine transition at nucleotide 479 resulting in the amino acid substitution of Arg-160 to Gln [17].

Anatomical context of SUOX

• The deficiencies can be diagnosed prenatally by monitoring sulfite oxidase activity in chorionic villus sampling (CVS) tissue [1].
• This precedes severe cystic encephalomalacia and suggests that the energy failure associated with neuronal dysfunction and myelin disintegration occurs early in isolated sulfite oxidase deficiency [18].
• Effect of sulfite on red blood cell deformability ex vivo and in normal and sulfite oxidase-deficient rats in vivo [19].
• Expressions of N-methyl-D: -aspartate receptors NR2A and NR2B subunit proteins in normal and sulfite-oxidase deficient rat's hippocampus: effect of exogenous sulfite ingestion [20].
• Liver tissue and hepatocytes, however, exhibit high activities of sulfite oxidase [21].

Associations of SUOX with chemical compounds

• The molybdenum- and iron-containing enzyme sulfite oxidase catalyzes the physiologically vital oxidation of sulfite to sulfate [15].
• Native sulfite oxidase was rapidly inactivated by phenylglyoxal, yielding a modified protein with kinetic parameters mimicking those of the R160Q mutant [17].
• These results demonstrate that the Tyr(343) residue is important for both substrate binding and oxidation of sulfite by sulfite oxidase [22].
• In the crystal structure of chicken sulfite oxidase, the residue Tyr(322) (Tyr(343) in human sulfite oxidase) was found to directly interact with a bound sulfate molecule and was proposed to have an important role in mediating the substrate specificity and catalytic activity of this molybdoprotein [22].
• The conversion of MPT into Moco by molybdate chelation apparently occurs concomitantly with the insertion of MPT into sulfite oxidase [2].

Other interactions of SUOX

• Molybdenum cofactor deficiency in humans results in the loss of the activity of molybdoenzymes sulfite oxidase, xanthine dehydrogenase, and aldehyde oxidase [16].
• The squash sequence has significant similarity to the amino acid sequences of sulfite oxidase, cytochrome b5, and NADH:cytochrome b5 reductase [23].
• The molybdenum cofactor is essential for the activity of the three molybdenum-containing enzymes, sulfite oxidase, xanthine oxidase and aldehyde oxidase [24].
• For ELISA, the pyruvate dehydrogenase or the ATPase-associated antigen fraction (M2), the sulfite oxidase fraction (M4), and the chromatographically purified M8-fraction should be used [25].
• In the second disorder of sulfite oxidase deficiency, the clinical presentation with progressive dystonia and dislocated lenses in an infant should suggest further laboratory investigations for this disorder which would not be detected by conventional laboratory screening procedures [26].

Analytical, diagnostic and therapeutic context of SUOX

• Prenatal diagnosis of molybdenum cofactor deficiency and isolated sulfite oxidase deficiency [1].
• Molecular cloning of human liver sulfite oxidase [27].
• The main alternative in the differential diagnosis of isolated sulfite oxidase deficiency is molybdenum cofactor deficiency [3].
• The relationship of these findings to a second patient recently identified as sulfite oxidase deficient and to an animal model of the disease are discussed [9].
• Coculture of group A and group B cells, without heterokaryon formation, led to the appearance of active sulfite oxidase [8].

References