allopurinol and Deficiency-Diseases

Topics: Aldehyde Oxidoreductases; Animals; Binding Sites; Biological Transport, Active; Ceruloplasmin; Copper; Cytochrome c Group; Deficiency Diseases; Erythropoiesis; Ferritins; Humans; Intestinal Absorption; Iron; Liver; Molybdenum; Nutritional Requirements; Oxidation-Reduction; Rats; Xanthine Oxidase

Topics: Alkaline Phosphatase; Animals; Bone and Bones; Catalase; Deficiency Diseases; Germ-Free Life; Intestinal Absorption; Intestines; Iron; Liver; Male; Oxidation-Reduction; Rabbits; Rats; Xanthine Oxidase; Zinc

Topics: Alcohol Oxidoreductases; Alkaline Phosphatase; Animals; Binding Sites; Carboxypeptidases; Catalysis; Deficiency Diseases; Dogs; Enzymes; Metals; Molybdenum; Nutritional Physiological Phenomena; Xanthine Oxidase; Zinc

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.

Topics: Antibody Formation; Antigen-Antibody Complex; Autopsy; Cross Reactions; Deficiency Diseases; Female; Heme; Humans; Liver; Molybdenum; Oxidoreductases; Pregnancy; Xanthine Oxidase

The administration of tungsten to rats maintained on a low molybdenum diet resulted in a dose- and time-dependent loss of sulfite oxidase (EC 1.8.3.1) and xanthine oxidase (EC 1.2.3.2) activities and hepatic molybdenum. These tungsten-treated animals appeared healthy, but were more susceptible to bisulfite toxicity. The median lethal dose for intraperitoneal bisulfite was found to be 181 mg of NaHSO(3) per kg for the animals deficient in sulfite oxidase, compared to 473 mg/kg for normal rats. The survival time of rats exposed to SO(2) at concentrations of 590 ppm and higher was seen to be inversely related to the level of SO(2). At 590 ppm and 925 ppm, control animals displayed symptoms of severe respiratory toxicity before death. At 2350 ppm of SO(2), death was preceded by seizures and prostration, symptoms observed with the systemic toxicity of injected bisulfite. At 590 ppm, animals deficient in sulfite oxidase were indistinguishable from control animals. However, at 925 ppm and 2350 ppm, the deficient animals displayed symptoms of systemic toxicity and had much shorter survival times. It is concluded that sulfite oxidase is instrumental in counteracting the toxic systemic effects of bisulfite, either injected or derived from respired SO(2). Respiratory death probably results from the toxicity of gaseous SO(2) before absorption as bisulfite and cannot be alleviated by sulfite oxidase. Sulfite oxidase does not appear to be inducible by either bisulfite or SO(2).

Topics: Animals; Biotransformation; Deficiency Diseases; Dose-Response Relationship, Drug; Liver; Male; Molybdenum; Oxidoreductases; Rats; Sulfites; Sulfur Dioxide; Tungsten; Xanthine Oxidase

Certain gouty subjects with excessive de novo purine synthesis are deficient in hypoxanthineguanine phosphoribosyltransferase (HG-PRTase [EC 2.4.2.8]). The mechanism of accelerated uric acid formation in these patients was explored by measuring the incorporation of glycine-(14)C into various urinary purine bases of normal and enzyme-deficient subjects during treatment with the xanthine oxidase inhibitor, allopurinol. In the presence of normal HG-PRTase activity, allopurinol reduced purine biosynthesis as demonstrated by diminished excretion of total urinary purine or by reduction of glycine-(14)C incorporation into hypoxanthine, xanthine, and uric acid to less than one-half of control values. A boy with the Lesch-Nyhan syndrome was resistant to this effect of allopurinol while a patient with 12.5% of normal enzyme activity had an equivocal response. Three patients with normal HG-PRTase activity had a mean molar ratio of hypoxanthine to xanthine in the urine of 0.28, whereas two subjects who were deficient in HG-PRTase had reversal of this ratio (1.01 and 1.04). The patterns of (14)C-labeling observed in HG-PRTase deficiency reflected the role of hypoxanthine as precursor of xanthine. The data indicate that excessive uric acid in HG-PRTase deficiency is derived from hypoxanthine which is insufficiently reutilized and, as a consequence thereof, catabolized inordinately to uric acid. The data provide evidence for cyclic interconversion of adenine and hypoxanthine derivatives. Cleavage of inosinic acid to hypoxanthine via inosine does not contribute significantly to the formation of uric acid in either normal man or in patients with HG-PRTase deficiency.HG-PRTase was not completely absent in red blood cells from a boy with the Lesch-Nyhan syndrome; with hypoxanthine as substrate, the activity in erythrocyte hemolysates was 0.64% of normal values.

Topics: Adult; Allopurinol; Athetosis; Carbon Isotopes; Child; Chorea; Compulsive Behavior; Deficiency Diseases; Glycine; Gout; Guanine; Humans; Hypoxanthines; Inositol; Intellectual Disability; Metabolism, Inborn Errors; Nucleosides; Purines; Self Mutilation; Transferases; Uric Acid

Topics: Animals; Deficiency Diseases; Diet; Enzyme Induction; Female; Growth; In Vitro Techniques; Intestines; Kidney; Liver; Lung; Male; Mitochondria, Liver; Oryza; Rats; Spleen; Succinate Dehydrogenase; Sweetening Agents; Tryptophan Oxygenase; Xanthine Oxidase

Topics: Alanine Transaminase; Alcohol Oxidoreductases; Alkaline Phosphatase; Animals; Aspartate Aminotransferases; Catalase; Deficiency Diseases; Glutamate Dehydrogenase; Intestinal Mucosa; Kidney; Liver; Rats; Uric Acid; Xanthine Oxidase; Zinc