Sulfites Abstracts 2

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Tungsten, the surprisingly positively acting heavy metal element for prokaryotes

            (Andreesen and Makdessi 2008) Download

The history and changing function of tungsten as the heaviest element in biological systems is given. It starts from an inhibitory element/anion, especially for the iron molybdenum-cofactor (FeMoCo)-containing enzyme nitrogenase involved in dinitrogen fixation, as well as for the many "metal binding pterin" (MPT)-, also known as tricyclic pyranopterin- containing classic molybdoenzymes, such as the sulfite oxidase and the xanthine dehydrogenase family of enzymes. They are generally involved in the transformation of a variety of carbon-, nitrogen- and sulfur-containing compounds. But tungstate can serve as a potential positively acting element for some enzymes of the dimethyl sulfoxide (DMSO) reductase family, especially for CO(2)-reducing formate dehydrogenases (FDHs), formylmethanofuran dehydrogenases and acetylene hydratase (catalyzing only an addition of water, but no redox reaction). Tungsten even becomes an essential element for nearly all enzymes of the aldehyde oxidoreductase (AOR) family. Due to the close chemical and physical similarities between molybdate and tungstate, the latter was thought to be only unselectively cotransported or cometabolized with other tetrahedral anions, such as molybdate and also sulfate. However, it has now become clear that it can also be very selectively transported compared to molybdate into some prokaryotic cells by two very selective ABC-type of transporters that contain a binding protein TupA or WtpA. Both proteins exhibit an extremely high affinity for tungstate (K(D) < 1 nM) and can even discriminate between tungstate and molybdate. By that process, tungsten finally becomes selectively incorporated into the few enzymes noted above.

Asthma with sulfite intolerance in children: a blocking study with cyanocobalamin

            (Anibarro, Caballero et al. 1992) Download

Sulfites have been implicated as the cause of bronchospasm in some subjects with asthma. However, there is still no universally accepted explanation of the pathogenesis of these reactions. We have studied five children with asthma with metabisulfite intolerance confirmed by oral challenge testing. The challenge test with metabisulfite was repeated after premedication of all the patients with 1.5 mg of oral cyanocobalamin. In four of the five patients treated with cyanocobalamin, bronchospasm did not develop in the second metabisulfite challenge. The possible mechanisms are discussed.

Sulfite oxidizing enzymes

            (Feng, Tollin et al. 2007) Download

Sulfite oxidizing enzymes are essential mononuclear molybdenum (Mo) proteins involved in sulfur metabolism of animals, plants and bacteria. There are three such enzymes presently known: (1) sulfite oxidase (SO) in animals, (2) SO in plants, and (3) sulfite dehydrogenase (SDH) in bacteria. X-ray crystal structures of enzymes from all three sources (chicken SO, Arabidopsis thaliana SO, and Starkeya novella SDH) show nearly identical square pyramidal coordination around the Mo atom, even though the overall structures of the proteins and the presence of additional cofactors vary. This structural information provides a molecular basis for studying the role of specific amino acids in catalysis. Animal SO catalyzes the final step in the degradation of sulfur-containing amino acids and is critical in detoxifying excess sulfite. Human SO deficiency is a fatal genetic disorder that leads to early death, and impaired SO activity is implicated in sulfite neurotoxicity. Animal SO and bacterial SDH contain both Mo and heme domains, whereas plant SO only has the Mo domain. Intraprotein electron transfer (IET) between the Mo and Fe centers in animal SO and bacterial SDH is a key step in the catalysis, which can be studied by laser flash photolysis in the presence of deazariboflavin. IET studies on animal SO and bacterial SDH clearly demonstrate the similarities and differences between these two types of sulfite oxidizing enzymes. Conformational change is involved in the IET of animal SO, in which electrostatic interactions may play a major role in guiding the docking of the heme domain to the Mo domain prior to electron transfer. In contrast, IET measurements for SDH demonstrate that IET occurs directly through the protein medium, which is distinctly different from that in animal SO. Point mutations in human SO can result in significantly impaired IET or no IET, thus rationalizing their fatal effects. The recent developments in our understanding of sulfite oxidizing enzyme mechanisms that are driven by a combination of molecular biology, rapid kinetics, pulsed electron paramagnetic resonance (EPR), and computational techniques are the subject of this review.

Pyridoxal 5'-phosphate in cerebrospinal fluid; factors affecting concentration

            (Footitt, Heales et al. 2011) Download

Analysis of pyridoxal 5'-phosphate (PLP) concentration in 256 cerebrospinal fluid (CSF) samples from patients with neurological symptoms showed that the variance is greater than indicated by previous studies. The age-related lower reference limit has been revised to detect inborn errors of metabolism that lead to PLP depletion without a high false positive rate: < 30 days, 26 nmol/L; 30 days to 12 months, 14 nmol/L; 1-2 years, 11 nmol/L; > 3 years, 10 nmol/L. Inborn errors leading to PLP concentrations below these values include pyridoxine-dependent epilepsy due to antiquitin deficiency, and molybdenum cofactor deficiency that leads to the accumulation of sulfite, a nucleophile capable of reacting with PLP. Low PLP levels were also seen in a group of children with transiently elevated urinary excretion of sulfite and/or sulfocysteine, suggesting that there may be other situations in which sulfite accumulates and inactivates PLP. There was no evidence that seizures or the anticonvulsant drugs prescribed for patients in this study led to significant lowering of CSF PLP. A small proportion of patients receiving L-dopa therapy were found to have a CSF PLP concentration below the appropriate reference range. This may have implications for monitoring and treatment. A positive correlation was seen between the CSF PLP and 5-methyl-tetrahydrofolate (5-MTHF) and tetrahydrobiopterin (BH(4)) concentrations. All are susceptible to attack by nucleophiles and oxygen-derived free-radicals, and CSF has relatively low concentrations of other molecules that can react with these compounds. Further studies of CSF PLP levels in a wide range of neurological diseases might lead to improved understanding of pathogenesis and possibilities for treatment.

Crystal structure of the S-adenosylmethionine-dependent enzyme MoaA and its implications for molybdenum cofactor deficiency in humans

            (Hanzelmann and Schindelin 2004) Download

The MoaA and MoaC proteins catalyze the first step during molybdenum cofactor biosynthesis, the conversion of a guanosine derivative to precursor Z. MoaA belongs to the S-adenosylmethionine (SAM)-dependent radical enzyme superfamily, members of which catalyze the formation of protein and/or substrate radicals by reductive cleavage of SAM by a [4Fe-4S] cluster. A defined in vitro system is described, which generates precursor Z and led to the identification of 5'-GTP as the substrate. The structures of MoaA in the apo-state (2.8 angstroms) and in complex with SAM (2.2 angstroms) provide valuable insights into its mechanism and help to define the defects caused by mutations in the human ortholog of MoaA that lead to molybdenum cofactor deficiency, a usually fatal disease accompanied by severe neurological symptoms. The central core of each subunit of the MoaA dimer is an incomplete triosephosphate isomerase barrel formed by the N-terminal part of the protein, which contains the [4Fe-4S] cluster typical for SAM-dependent radical enzymes. SAM is the fourth ligand to the cluster and binds to its unique Fe as an N/O chelate. The lateral opening of the incomplete triosephosphate isomerase barrel is covered by the C-terminal part of the protein containing an additional [4Fe-4S] cluster, which is unique to MoaA proteins. Both FeS clusters are separated by approximately 17 angstroms, with a large active site pocket between. The noncysteinyl-ligated unique Fe site of the C-terminal [4Fe-4S] cluster is proposed to be involved in the binding and activation of 5'-GTP.

Human sulfite oxidase deficiency. Characterization of the molecular defect in a multicomponent system

            (Johnson and Rajagopalan 1976) Download

Frozen liver tissue from an individual identified several years ago as sulfite oxidase deficient has been reexamined in light of new knowledge which has been obtained regarding the enzyme. It has been established that hepatic molybdenum levels and xanthine oxidase activity were within normal values and comparable to those observed in control samples preserved from the original study along with the deficient tissue sample. 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. Using an antibody preparation directed against rat liver sulfite oxidase which also inhibits and precipitates the human enzyme, it has been determined that cross-reacting material with determinants recognized by inhibiting antibodies is absent in the liver sample from the deficient patient. Immunodiffusion experiments gave strong precipitin bands against the control liver extracts, but showed no detectable precipitin reaction between the deficient liver extract and the antibody preparation. 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.

Iron-sulfur proteins as initiators of radical chemistry

            (Marquet, Bui et al. 2007) Download

Iron-sulfur proteins are very versatile biological entities for which many new functions are continuously being unravelled. This review focus on their role in the initiation of radical chemistry, with special emphasis on radical-SAM enzymes, since several members of the family catalyse key steps in the biosynthetic pathways of cofactors such as biotin, lipoate, thiamine, heme and the molybdenum cofactor. It will also include other examples to show the chemical logic which is emerging from the presently available data on this family of enzymes. The common step in all the (quite different) reactions described here is the monoelectronic reductive cleavage of SAM by a reduced [4Fe-4S](1+) cluster, producing methionine and a highly oxidising deoxyadenosyl radical, which can initiate chemically difficult reactions. This set of enzymes, which represent a means to perform oxidation under reductive conditions, are often present in anaerobic organisms. Some other, non-SAM-dependent, radical reactions obeying the same chemical logic are also covered.

Cell biology of molybdenum

            (Mendel 2009) Download

The transition element molybdenum (Mo) is an essential micronutrient that is needed as catalytically active metal during enzyme catalysis. In humans four enzymes depend on Mo: sulfite oxidase, xanthine oxidoreductase, aldehyde oxidase, and mitochondrial amidoxime reductase. In addition to these enzymes, plants harbor a fifth Mo-enzyme namely nitrate reductase. To gain biological activity and fulfill its function in enzymes, Mo has to be complexed by a pterin compound thus forming the molybdenum cofactor. This article will review the way that Mo takes from uptake into the cell, via formation of the molybdenum cofactor and its storage, up to the final insertion of the molybdenum cofactor into apometalloenzymes.

Biology of the molybdenum cofactor

            (Mendel 2007) Download

The transition element molybdenum (Mo) is an essential micronutrient for plants where it is needed as a catalytically active metal during enzyme catalysis. Four plant enzymes depend on molybdenum: nitrate reductase, sulphite oxidase, xanthine dehydrogenase, and aldehyde oxidase. However, in order to gain biological activity and fulfil its function in enzymes, molybdenum has to be complexed by a pterin compound thus forming the molybdenum cofactor. In this article, the path of molybdenum from its uptake into the cell, via formation of the molybdenum cofactor and its storage, to the final modification of the molybdenum cofactor and its insertion into apo-metalloenzymes will be reviewed.

Heavy metal ions inhibit molybdoenzyme activity by binding to the dithiolene moiety of molybdopterin in Escherichia coli

            (Neumann and Leimkuhler 2008) Download

Molybdenum insertion into the dithiolene group on the 6-alkyl side-chain of molybdopterin is a highly specific process that is catalysed by the MoeA and MogA proteins in Escherichia coli. Ligation of molybdate to molybdopterin generates the molybdenum cofactor, which can be inserted directly into molybdoenzymes binding the molybdopterin form of the molybdenum cofactor, or is further modified in bacteria to form the dinucleotide form of the molybdenum cofactor. The ability of various metals to bind tightly to sulfur-rich sites raised the question of whether other metal ions could be inserted in place of molybdenum at the dithiolene moiety of molybdopterin in molybdoenzymes. We used the heterologous expression systems of human sulfite oxidase and Rhodobacter sphaeroides dimethylsulfoxide reductase in E. coli to study the incorporation of different metal ions into the molybdopterin site of these enzymes. From the added metal-containing compounds Na(2)MoO(4), Na(2)WO(4), NaVO(3), Cu(NO(3))(2), CdSO(4) and NaAsO(2) during the growth of E. coli, only molybdate and tungstate were specifically inserted into sulfite oxidase and dimethylsulfoxide reductase. Other metals, such as copper, cadmium and arsenite, were nonspecifically inserted into sulfite oxidase, but not into dimethylsulfoxide reductase. We showed that metal insertion into molybdopterin occurs beyond the step of molybdopterin synthase and is independent of MoeA and MogA proteins. Our study shows that the activity of molybdoenzymes, such as sulfite oxidase, is inhibited by high concentrations of heavy metals in the cell, which will help to further the understanding of metal toxicity in E. coli.

Demonstration of autoantibodies to recombinant human sulphite oxidase in patients with chronic liver disorders and analysis of their clinical relevance

            (Preuss, Berg et al. 2007) Download

It has been shown previously that sera from patients with cholestatic liver diseases react with sulphite oxidase (SO) prepared from chicken liver. In order to analyse this reactivity and the clinical relevance of anti-SO antibodies in more detail, we produced human recombinant SO. Human recombinant SO (60 kDa) was expressed in Escherichia coli and applied to enzyme-linked immunosorbent assay and Western blot. Sera from patients with autoimmune liver disorders [primary biliary cirrhosis (PBC) n = 96; autoimmune hepatitis (AIH) n = 77; primary sclerosing cholangitis (PSC) n = 39], and from patients with other hepatic (n = 154) and non-hepatic chronic inflammatory disorders (n = 113) were investigated. Highest incidence and activities of IgG-anti-SO antibodies were observed in PSC patients. Nine of 16 untreated (56%) and four of 23 PSC patients treated with ursodeoxycholic acid (UDCA) (17%) were positive. Antibody activity decreased significantly during UDCA treatment. Five per cent of PBC and 9% of AIH patients, but also 15% of patients with alcoholic liver disease, were IgG anti-SO-positive. In patients with viral hepatitis and non-hepatic disorders they could be hardly detected. Anti-SO antibodies are further anti-mitochondrial antibodies in chronic liver diseases. They occur predominantly in PSC, and UDCA treatment seams to decrease antibody activity. Whether these antibodies are primary or secondary phenomena and whether they are related to the aetiology or pathogenesis, at least in a subgroup of patients with chronic liver diseases, has still to be evaluated.

Protein Radical Formation Resulting from Eosinophil Peroxidase-catalyzed Oxidation of Sulfite

            (Ranguelova, Chatterjee et al. 2010) Download

Eosinophil peroxidase (EPO) is an abundant heme protein in eosinophils that catalyzes the formation of cytotoxic oxidants implicated in asthma, allergic inflammatory disorders, and cancer. It is known that some proteins with peroxidase activity (horseradish peroxidase and prostaglandin hydroperoxidase) can catalyze oxidation of bisulfite (hydrated sulfur dioxide), leading to the formation of sulfur trioxide anion radical ((.)SO(3)(-)). This free radical further reacts with oxygen to form peroxymonosulfate anion radical ((-)O(3)SOO(.)) and the very reactive sulfate anion radical (SO(4)()), which is nearly as strong an oxidant as the hydroxyl radical. However, the ability of EPO to generate reactive sulfur radicals has not yet been reported. Here we demonstrate that eosinophil peroxidase/H(2)O(2) is able to oxidize bisulfite, ultimately forming the sulfate anion radical (SO(4)()), and that these reactive intermediates can oxidize target proteins to protein radicals, thereby initiating protein oxidation. We used immuno-spin trapping and confocal microscopy to study protein oxidation by EPO/H(2)O(2) in the presence of bisulfite in a pure enzymatic system and in human promyelocytic leukemia HL-60 clone 15 cells, maturated to eosinophils. Polyclonal antiserum raised against the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) detected the presence of DMPO covalently attached to the proteins resulting from the DMPO trapping of protein free radicals. We found that sulfite oxidation mediated by EPO/H(2)O(2) induced the formation of radical-derived DMPO spin-trapped human serum albumin and, to a lesser extent, of DMPO-EPO. These studies suggest that EPO-dependent oxidative damage may play a role in tissue injury in bisulfite-exacerbated eosinophilic inflammatory disorders.

Santamaria-Araujo 2004 - The tetrahydropyranopterin structure of the sulfur-free and metal-free molybdenum cofactor precursor

            (Santamaria-Araujo, Fischer et al. 2004) Download

The molybdenum cofactor (Moco), a highly conserved pterin compound coordinating molybdenum (Mo), is required for the activity of all Mo-dependent enzymes with the exception of nitrogenase. Moco is synthesized by a unique and evolutionary old multi-step pathway with two intermediates identified so far, the sulfur-free and metal-free pterin derivative precursor Z and molybdopterin, a pterin with an enedithiolate function essential for Mo ligation. The latter pterin component is believed to form a tetrahydropyranopterin similar to the one found for Moco in the crystal structure of Mo as well as tungsten (W) enzymes. Here we report the spectroscopic characterization and structure elucidation of precursor Z purified from Escherichia coli overproducing MoaA and MoaC, two proteins essential for bacterial precursor Z synthesis. We have shown that purified precursor Z is as active as precursor Z present in E. coli cell extracts, demonstrating that no modifications during the purification procedure have occurred. High resolution electrospray ionization mass spectrometry afforded a [M + H]+ ion compatible with a molecular formula of C10H15N5O8P. Consequently 1H NMR spectroscopy not allowed structural characterization of the molecule but confirmed that this intermediate undergoes direct oxidation to the previously well characterized non-productive follow-up product compound Z. The 1H chemical shift and coupling constant data are incompatible with previous structural proposals and indicate that precursor Z already is a tetrahydropyranopterin system and carries a geminal diol function in the C1' position.

Molybdenum cofactors, enzymes and pathways.

            (Schwarz, Mendel et al. 2009) Download

The trace element molybdenum is essential for nearly all organisms and forms the catalytic centre of a large variety of enzymes such as nitrogenase, nitrate reductases, sulphite oxidase and xanthine oxidoreductases. Nature has developed two scaffolds holding molybdenum in place, the iron-molybdenum cofactor and pterin-based molybdenum cofactors. Despite the different structures and functions of molybdenum-dependent enzymes, there are important similarities, which we highlight here. The biosynthetic pathways leading to both types of cofactor have common mechanistic aspects relating to scaffold formation, metal activation and cofactor insertion into apoenzymes, and have served as an evolutionary 'toolbox' to mediate additional cellular functions in eukaryotic metabolism.

Molybdenum cofactor biosynthesis and deficiency

            (Schwarz 2005) Download

The molybdenum cofactor (Moco) forms the active site of all molybdenum (Mo) enzymes, except nitrogenase. Mo enzymes catalyze important redox reactions in global metabolic cycles. Moco consists of Mo covalently bound to one or two dithiolates attached to a unique tricyclic pterin moiety commonly referred to as molybdopterin (MPT). Moco is synthesized by an ancient and conserved biosynthetic pathway that can be divided into four steps, according to the biosynthetic intermediates precursor Z (cyclic pyranopterin monophosphate), MPT and adenylated MPT. In a fifth step modifications such as attachment of nucleotides, sulfuration or bond formation between Mo and the protein result in different catalytic Mo centers. A defect in any of the steps of Moco biosynthesis results in the pleiotropic loss of all Mo enzyme activities. Human Moco deficiency is a hereditary metabolic disorder characterized by severe neurodegeneration resulting in early childhood death. Recently, a first substitution therapy was established.

Genetic studies of a cluster of acute lymphoblastic leukemia cases in Churchill County, Nevada

            (Steinberg, Relling et al. 2007) Download

OBJECTIVE: In a study to identify exposures associated with 15 cases of childhood leukemia, we found levels of tungsten, arsenic, and dichlorodiphenyldichloroethylene in participants to be higher than mean values reported in the National Report on Human Exposure to Environmental Chemicals. Because case and comparison families had similar levels of these contaminants, we conducted genetic studies to identify gene polymorphisms that might have made case children more susceptible than comparison children to effects of the exposures. DESIGN: We compared case with comparison children to determine whether differences existed in the frequency of polymorphic genes, including genes that code for enzymes in the folate and purine pathways. We also included discovery of polymorphic forms of genes that code for enzymes that are inhibited by tungsten: xanthine dehydrogenase, sulfite oxidase (SUOXgene), and aldehyde oxidase. PARTICIPANTS: Eleven case children were age- and sex-matched with 42 community comparison children for genetic analyses. Twenty parents of case children also contributed to the analyses. RESULTS: One bilalleleic gene locus in SUOX was significantly associated with either case or comparison status, depending on which alleles the child carried (without adjusting for multiple comparisons). CONCLUSIONS: Although genetic studies did not provide evidence that a common agent or genetic susceptibility factor caused the leukemias, the association between a SUOXgene locus and disease status in the presence of high tungsten and arsenic levels warrants further investigation. RELEVANCE: Although analyses of community clusters of cancer have rarely identified causes, these findings have generated hypotheses to be tested in subsequent studies.

Asthma and anaphylactoid reactions to food additives

            (Tarlo and Sussman 1993) Download

Presumed allergic reactions to hidden food additives are both controversial and important. Clinical manifestations include asthma, urticaria, angioedema, and anaphylactic-anaphylactoid events. Most adverse reactions are caused by just a few additives, such as sulfites and monosodium glutamate. Diagnosis is suspected from the history and confirmed by specific challenge. The treatment is specific avoidance.

Successful treatment of molybdenum cofactor deficiency type A with cPMP

            (Veldman, Santamaria-Araujo et al. 2010) Download

Molybdenum cofactor deficiency (MoCD) is a rare metabolic disorder characterized by severe and rapidly progressive neurologic damage caused by the functional loss of sulfite oxidase, 1 of 4 molybdenum-dependent enzymes. To date, no effective therapy is available for MoCD, and death in early infancy has been the usual outcome. We report here the case of a patient who was diagnosed with MoCD at the age of 6 days. Substitution therapy with purified cyclic pyranopterin monophosphate (cPMP) was started on day 36 by daily intravenous administration of 80 to 160 microg of cPMP/kg of body weight. Within 1 to 2 weeks, all urinary markers of sulfite oxidase (sulfite, S-sulfocysteine, thiosulfate) and xanthine oxidase deficiency (xanthine, uric acid) returned to almost normal readings and stayed constant (>450 days of treatment). Clinically, the infant became more alert, convulsions and twitching disappeared within the first 2 weeks, and an electroencephalogram showed the return of rhythmic elements and markedly reduced epileptiform discharges. Substitution of cPMP represents the first causative therapy available for patients with MoCD. We demonstrate efficient uptake of cPMP and restoration of molybdenum cofactor-dependent enzyme activities. Further neurodegeneration by toxic metabolites was stopped in the reported patient. We also demonstrated the feasibility to detect MoCD in newborn-screening cards to enable early diagnosis.

Complex biotransformations catalyzed by radical S-adenosylmethionine enzymes

            (Zhang and Liu 2011) Download

The radical S-adenosylmethionine (AdoMet) superfamily currently comprises thousands of proteins that participate in numerous biochemical processes across all kingdoms of life. These proteins share a common mechanism to generate a powerful 5'-deoxyadenosyl radical, which initiates a highly diverse array of biotransformations. Recent studies are beginning to reveal the role of radical AdoMet proteins in the catalysis of highly complex and chemically unusual transformations, e.g. the ThiC-catalyzed complex rearrangement reaction. The unique features and intriguing chemistries of these proteins thus demonstrate the remarkable versatility and sophistication of radical enzymology.


Andreesen, J. R. and K. Makdessi (2008). "Tungsten, the surprisingly positively acting heavy metal element for prokaryotes." Ann N Y Acad Sci 1125: 215-29.

Anibarro, B., T. Caballero, et al. (1992). "Asthma with sulfite intolerance in children: a blocking study with cyanocobalamin." J Allergy Clin Immunol 90(1): 103-9.

Feng, C., G. Tollin, et al. (2007). "Sulfite oxidizing enzymes." Biochim Biophys Acta 1774(5): 527-39.

Footitt, E. J., S. J. Heales, et al. (2011). "Pyridoxal 5'-phosphate in cerebrospinal fluid; factors affecting concentration." J Inherit Metab Dis 34(2): 529-38.

Hanzelmann, P. and H. Schindelin (2004). "Crystal structure of the S-adenosylmethionine-dependent enzyme MoaA and its implications for molybdenum cofactor deficiency in humans." Proc Natl Acad Sci U S A 101(35): 12870-5.

Johnson, J. L. and K. V. Rajagopalan (1976). "Human sulfite oxidase deficiency. Characterization of the molecular defect in a multicomponent system." J Clin Invest 58(3): 551-6.

Marquet, A., B. T. Bui, et al. (2007). "Iron-sulfur proteins as initiators of radical chemistry." Nat Prod Rep 24(5): 1027-40.

Mendel, R. R. (2007). "Biology of the molybdenum cofactor." J Exp Bot 58(9): 2289-96.

Mendel, R. R. (2009). "Cell biology of molybdenum." Biofactors 35(5): 429-34.

Neumann, M. and S. Leimkuhler (2008). "Heavy metal ions inhibit molybdoenzyme activity by binding to the dithiolene moiety of molybdopterin in Escherichia coli." FEBS J 275(22): 5678-89.

Preuss, B., C. Berg, et al. (2007). "Demonstration of autoantibodies to recombinant human sulphite oxidase in patients with chronic liver disorders and analysis of their clinical relevance." Clin Exp Immunol 150(2): 312-21.

Ranguelova, K., S. Chatterjee, et al. (2010). "Protein Radical Formation Resulting from Eosinophil Peroxidase-catalyzed Oxidation of Sulfite." J Biol Chem 285(31): 24195-205.

Santamaria-Araujo, J. A., B. Fischer, et al. (2004). "The tetrahydropyranopterin structure of the sulfur-free and metal-free molybdenum cofactor precursor." J Biol Chem 279(16): 15994-9.

Schwarz, G. (2005). "Molybdenum cofactor biosynthesis and deficiency." Cell Mol Life Sci 62(23): 2792-810.

Schwarz, G., R. R. Mendel, et al. (2009). "Molybdenum cofactors, enzymes and pathways." Nature 460(7257): 839-47.

Steinberg, K. K., M. V. Relling, et al. (2007). "Genetic studies of a cluster of acute lymphoblastic leukemia cases in Churchill County, Nevada." Environ Health Perspect 115(1): 158-64.

Tarlo, S. M. and G. L. Sussman (1993). "Asthma and anaphylactoid reactions to food additives." Can Fam Physician 39: 1119-23.

Veldman, A., J. A. Santamaria-Araujo, et al. (2010). "Successful treatment of molybdenum cofactor deficiency type A with cPMP." Pediatrics 125(5): e1249-54.

Zhang, Q. and W. Liu (2011). "Complex biotransformations catalyzed by radical S-adenosylmethionine enzymes." J Biol Chem 286(35): 30245-52.