molybdenum-cofactor and urothion

Urothione was isolated as an excretion product of Hydrogenophaga pseudoflava and other bacteria at amounts approaching 253 micrograms/l of culture corresponding to 44 micrograms/g bacterial dry mass. The compound was identified as urothione by co-chromatography with urothione isolated from human urine, its characteristic ultraviolet and visible absorption spectra, oxidation to pterin-6-carboxylic-7-sulfonic acid by alkaline permanganate, 1H-NMR spectroscopy, double-quantum-filtered Fourier-transform 1H correlated spectroscopy, circular-dichroism spectroscopy and mass spectroscopy. A metabolic relationship between urothione and the carbon monoxide dehydrogenase molybdenum cofactor was suggested by a 1.1:0.5 molar ratio between urothione excreted and degradation of carbon monoxide dehydrogenase, a coincidence of urothione excretion and induction of carbon monoxide dehydrogenase with different species of carboxidotrophic bacteria, a structural relationship between molybdopterin cytosine dinucleotide of the carbon monoxide dehydrogenase molybdenum cofactor and urothione, and the demonstrated conversion of the carbon monoxide dehydrogenase molybdenum cofactor to urothione in vitro. A pathway for the conversion of the H. pseudoflava carbon monoxide dehydrogenase molybdenum cofactor to urothione has been proposed which involves molybdopterin cytosine dinucleotide, molybdopterin, phospho-norurothione and norurothione.

Topics: Aldehyde Oxidoreductases; Coenzymes; Magnetic Resonance Spectroscopy; Metalloproteins; Molecular Structure; Molybdenum Cofactors; Multienzyme Complexes; Pseudomonas; Pteridines

Molybdenum cofactor deficiency was diagnosed in a 3-month-old girl who presented with microcephaly, developmental delay, severe irritability, and lactic acidosis. Dietary methionine restriction, with cysteine supplementation, was associated with moderate short-term clinical improvement, including a resumption in predicted head growth, modest developmental progress, and a reduction in irritability. Clinical relapse was associated with noncompliance of dietary therapy 2 months later. Urinary sulfite levels measured by commercial dipsticks were useful in following therapy. Molybdenum cofactor deficiency is probably frequently underdiagnosed due to the lack of specific clinical or laboratory features. Screening of infants at risk for the presence of urinary sulfites or serum hypouricemia, or both, is both rapid and inexpensive.

Topics: Acidosis, Lactic; Coenzymes; Cysteine; Developmental Disabilities; Female; Food, Fortified; Humans; Infant; Lactates; Metabolism, Inborn Errors; Metalloproteins; Methionine; Microcephaly; Molybdenum Cofactors; Pteridines

Topics: Biomarkers; Coenzymes; Humans; Metabolism, Inborn Errors; Metalloproteins; Molybdenum; Molybdenum Cofactors; Pteridines; Pterins

A girl aged eight months, who presented with developmental delay and dislocated optic lenses, was diagnosed as having combined sulfite oxidase and xanthine dehydrogenase deficiencies consistent with molybdenum cofactor deficiency. The diagnosis was confirmed by demonstrating the absence in urine of urothione, a molybdenum cofactor metabolite. Prenatal diagnosis excluded the disease in the mother's second pregnancy. A summary of an in vitro study of molybdenum cofactor synthesis in the patient is given.

Topics: Coenzymes; Female; Humans; Infant; Male; Metalloproteins; Molecular Structure; Molybdenum Cofactors; Oxidoreductases Acting on Sulfur Group Donors; Pregnancy; Prenatal Diagnosis; Pteridines; Xanthine Dehydrogenase

Increased urinary excretion of xanthine, hypoxanthine, sulphite, thiosulphate and decreased serum uric acid were observed in an infant with profound failure to thrive. Other clinical findings included refractory seizures, spastic quadriplegia and profound psychomotor retardation. The patient died at 20 months of age. There were no detectable activities for xanthine oxidase and sulphite oxidase in the postmortem liver. Urothione, which is the metabolic excretory product of the molybdenum cofactor for molybdoenzymes was not present in the urine. A deficiency of the molybdenum cofactor which is common to both xanthine and sulphite oxidase is presumed to be the metabolic defect responsible for the absent activities of both enzymes.

Topics: Coenzymes; Humans; Infant, Newborn; Liver; Male; Metabolism, Inborn Errors; Metalloproteins; Molybdenum Cofactors; Oxidoreductases; Oxidoreductases Acting on Sulfur Group Donors; Pteridines; Sulfites; Xanthine; Xanthine Oxidase; Xanthines

The molybdenum cofactor isolated from sulfite oxidase (sulfite: ferricytochrome c oxidoreductase, EC 1.8.2.1) and xanthine dehydrogenase (xanthine:NAD+ oxidoreductase, EC 1.2.1.37) in the presence of iodine and KI (form A) has been shown to contain a pterin nucleus with an unidentified substituent in the 6 position [Johnson, J. L., Hainline, B. E. & Rajagopalan, K. V. (1980) J. Biol. Chem. 255, 1783-1786]. A second inactive form of the cofactor was isolated aerobically but in the absence of iodine and KI. The latter cofactor derivative (form B) is highly fluorescent, has a visible absorption band at 395 nm and, like form A, contains a phosphate group. Cleavage of the phosphate ester bond with alkaline phosphatase exposes a glycol function that is sensitive to periodate. Oxidation of form B with alkaline permanganate yields a highly polar compound with properties of a sulfonic acid, suggesting that the active molybdenum cofactor might contain sulfur. The sulfur-containing pterin urothione characterized by Goto et al. [Goto, M., Sakurai, A., Ohta, K. & Yamakami, H. (1969) J. Biochem. 65, 611-620] had been isolated from human urine. The permanganate oxidation product of urothione, characterized by Goto et al. as pterin-6-carboxylic-7-sulfonic acid, is identical to that obtained from form B. Because urothione also contains a periodate-sensitive glycol substituent, a structural relationship is suggested. The finding that urine samples from patients deficient in the molybdenum cofactor are devoid of urothione demonstrates a metabolic link between the two molecules.

Topics: Animals; Chickens; Coenzymes; Liver; Metalloproteins; Molybdenum; Molybdenum Cofactors; Oxidation-Reduction; Oxidoreductases; Oxidoreductases Acting on Sulfur Group Donors; Pteridines; Spectrometry, Fluorescence; Spectrophotometry