ascorbic-acid and Metabolism--Inborn-Errors

We report a child with an isolated complex III respiratory chain deficiency and global developmental delay who had severe pruritus with elevated plasma bile acid levels. A liver biopsy showed micronodular cirrhosis, and enzymologic evaluation demonstrated an isolated complex III deficiency in both liver and muscle. His pruritus improved and serum bile acid levels decreased after treatment with menadione and vitamin C.

Topics: Anemia, Iron-Deficiency; Ascorbic Acid; Bile Acids and Salts; Child, Preschool; Developmental Disabilities; Drug Therapy, Combination; Electron Transport; Electron Transport Complex III; Humans; Male; Metabolism, Inborn Errors; Pruritus; Vitamin K

Topics: Ascorbic Acid; Diet; Glyoxylates; Humans; Hyperoxaluria; Hyperoxaluria, Primary; Intestinal Absorption; Kidney; Metabolism, Inborn Errors; Oxalates

Topics: Ascorbic Acid; Humans; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Metabolism, Inborn Errors; Oxalates; Oxalic Acid; Peritoneal Dialysis, Continuous Ambulatory; Renal Dialysis; Thiamine Deficiency; Vitamin B 6 Deficiency

This monograph on the clinical chemistry of vitamin B12 reviews the literature on daily requirements, methods for measurement, the effects of drugs on vitamin B12 metabolism absorption, pregnancy, clinical conditions associated with vitamin B12 deficiency, errors of metabolism, and reactions to vitamin therapy. Although only very small quantities of vitamin B12 are required to satisfy the daily requirement, a sufficient supply is stored in the liver to meet normal requirements for at least a 3-year period. A number of drugs are known to affect the absorption of vitamin B12, including neomycin, potassium chloride, p-aminosalicylic acid, and colchicine. Significantly reduced serum concentrations of vitamin B12 have been noted in users of oral contraceptives (OCs), although concentrations still remain within the limits of normal. It appears that the vitamin B12 level in OC users reestablishes itself at a different and somewhat lower level. Vitamin B12 binding protein appears to remain unchanged. A vitamin B12 deficiency is unusual in pregnant women who consume a normal, varied diet. On the other hand, lactating women whose diets are low in animal protein and dairy products may have problems providing enough vitamin B12 to meet their own and their infant's needs; supplementary oral vitamins should be considered.

Topics: Absorption; Adult; Alcoholism; Anemia, Pernicious; Ascorbic Acid; Autoantibodies; Biguanides; Biological Transport; Chemical Phenomena; Chemistry; Chlorpromazine; Contraceptives, Oral; Diet; Female; Gastrectomy; Gastritis; Humans; Intrinsic Factor; Malabsorption Syndromes; Male; Metabolism, Inborn Errors; Middle Aged; Neoplasms; Nervous System Diseases; Nitrous Oxide; Nutritional Requirements; Pancreatic Diseases; Parasitic Diseases; Pregnancy; Pregnancy Complications; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adrenal Glands; Ascorbic Acid; Centrifugation; Cyclic AMP; Gastric Mucosa; Histological Techniques; Luminescent Measurements; Metabolism, Inborn Errors; Microbiological Techniques; Microchemistry; Peptide Hydrolases; Prenatal Diagnosis; Radioimmunoassay; Spectrometry, Fluorescence; Spectrophotometry; Subcellular Fractions

Topics: Animals; Ascorbic Acid; Calcium; Chemical Phenomena; Chemistry; Child, Preschool; Diet; Glycine; Glycolates; Humans; Hydrogen-Ion Concentration; Isoenzymes; L-Lactate Dehydrogenase; Male; Metabolism, Inborn Errors; Mitochondria, Liver; Nutritional Physiological Phenomena; Oxalates; Rats; Solubility; Urinary Calculi

Topics: Ascorbic Acid; Bone and Bones; Calcium; Cell Membrane Permeability; Erythrocytes; Feces; Glycine; Humans; Intestinal Absorption; Intestinal Mucosa; Kidney; Kidney Diseases; Kidney Function Tests; Liver; Metabolism, Inborn Errors; Microsomes; Mitochondria; Muscles; Oxalates; Plants, Edible; Urinary Calculi

It is thought that vitamin C has protective roles on stress-induced heart damage and the development of cardiovascular diseases, but its precise role and mechanisms are unclear. In the present study, we investigated the specific mechanisms by which vitamin C leads to protecting the heart from stress-induced damage in the Gulo(-/-) mice which cannot synthesize vitamin C like humans. By exposure to stress (1h/day), the heartbeat and cardiac output in vitamin C-insufficient Gulo(-/-) mice were definitely decreased, despite a significant increase of adrenaline (ADR) and noradrenaline (NA) production. A change of cardiac structure caused by the death of cardiomyocytes and an increased expression of matrix metalloprotease (MMP)-2 and -9 were also found. Moreover, lipid peroxidation and the production of tumor necrosis factor-alpha (TNF-α) in the heart were increased. Finally, all vitamin C-insufficient Gulo(-/-) mice were expired within 2 weeks. Interestingly, all of the findings in vitamin C-insufficient Gulo(-/-) mice were completely prevented by the supplementation of a sufficient amount of vitamin C. Taken together, vitamin C insufficiency increases the risk of stress-induced cardiac damage with structural and functional changes arising from the apoptosis of cardiomyocytes.

Topics: Animals; Ascorbic Acid; Catecholamines; Down-Regulation; Echocardiography; Enzyme-Linked Immunosorbent Assay; Fluorescent Antibody Technique; Heart; Immunoblotting; Metabolism, Inborn Errors; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocytes, Cardiac; Oxidative Stress; Reactive Oxygen Species; Stress, Psychological; Tumor Necrosis Factor-alpha

A 45-month-old girl with 5-oxoprolinuria (pyroglutamic aciduria), hemolysis, and marked glutathione depletion caused by deficiency of glutathione synthetase was followed before and during treatment with ascorbate or N-acetylcysteine. High doses of ascorbate (0.7 mmol/kg per day) or N-acetylcysteine (6 mmol/kg per day) were given for 1 to 2 weeks without any obvious deleterious side effects. Ascorbate markedly increased lymphocyte (4-fold) and plasma (8-fold) levels of glutathione. N-Acetylcysteine also increased lymphocyte (3.5-fold) and plasma (6-fold) levels of glutathione. After these treatments were discontinued, lymphocyte and plasma glutathione levels decreased rapidly to pretreatment levels. Ascorbate treatment was extended for 1 year, and lymphocyte (4-fold) and plasma (2- to 5-fold) glutathione levels remained elevated above baseline. In parallel, the hematocrit increased from 25.4% to 32.6%, and the reticulocyte count decreased from 11% to 4%. The results demonstrate that ascorbate and N-acetylcysteine can decrease erythrocyte turnover in patients with hereditary glutathione deficiency by increasing glutathione levels.

Topics: Acetylcysteine; Ascorbic Acid; Child, Preschool; Female; Glutathione Synthase; Humans; Lymphocytes; Metabolism, Inborn Errors; Vitamin E

The bioenergetic capacity of skeletal muscle in a 17-year-old patient with a severe defect in complex III of the electron transport chain has been examined by 31P NMR measurements of the molar ratio of phosphocreatine to inorganic phosphate (PCr/Pi). Resting ratios were 1.3-2.5, which can be compared with roughly 8.6 for a young, normal female control at rest. Quantitative evaluation of the activity of oxidative metabolism was afforded by the rate of recovery of PCr/Pi from exercise and was found to be 2.5% of normal. After administration of menadione and ascorbate, we found a 21-fold increase of the recovery rate relative to the pretherapy value, to within 56% of the recovery rate of the young female control. Thus, NMR examinations of skeletal muscle at rest and in recovery from activity document marked improvement to specific drug therapy in the electron transport capabilities and the ATP synthesis rate of a patient with a deficiency in a cytochrome b-containing complex III. Improvements in functional ability, although not as dramatic as biochemical changes, are also apparent.

Topics: Adenosine Triphosphate; Ascorbic Acid; Electron Transport; Humans; Magnetic Resonance Spectroscopy; Metabolism, Inborn Errors; Mitochondria, Muscle; Oxidative Phosphorylation; Phosphocreatine; Vitamin K

The clinical and biochemical findings in a four-year-old girl with prolidase deficiency, treated with L-proline, manganese and ascorbic acid, are presented.

Topics: Ascorbic Acid; Child, Preschool; Collagen; Dipeptidases; Dipeptides; Female; Humans; Manganese; Metabolism, Inborn Errors; Proline; Skin

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Female; Guinea Pigs; Humans; L-Gulonolactone Oxidase; Lactones; Metabolism, Inborn Errors; Nutritional Requirements; Sugar Alcohol Dehydrogenases

Large amounts of ascorbic acid occur occasionally in the urine of children being investigated for possible inherited metabolic disease and may give a positive ninhydrin reaction after thin-layer chromatography. As this compound is unstable in urine and runs with valine in a solvent system commonly used for preliminary screening, it is a possible source of confusion.

Topics: Ascorbic Acid; Child; Child, Preschool; Chromatography, Thin Layer; Genetic Testing; Humans; Infant; Metabolism, Inborn Errors; Ninhydrin; Specimen Handling; Valine

Topics: Amino Acids, Sulfur; Ascorbic Acid; Aspirin; Cysteamine; Cystinosis; Dipyridamole; Glutathione; Glutathione Synthase; Homocystinuria; Humans; Metabolism, Inborn Errors; Pyridoxine; Vitamin E

Topics: Adolescent; Adult; Ascorbic Acid; Child; Female; Humans; Male; Metabolism, Inborn Errors; Oxalates

Topics: Amines; Amino Acid Metabolism, Inborn Errors; Ascorbic Acid; Carbohydrate Metabolism, Inborn Errors; Female; Glucose; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Lipid Metabolism, Inborn Errors; Male; Metabolism, Inborn Errors; Peptides; Phosphatidylcholines; Ribose

Topics: Ascorbic Acid; Deficiency Diseases; Diet; Humans; Infections; Metabolism, Inborn Errors; Vitamins

Topics: Ascorbic Acid; Cyanosis; Dihydrolipoamide Dehydrogenase; Erythrocytes; Female; Heterozygote; Humans; Intestines; Kinetics; Metabolism, Inborn Errors; Methemoglobin; Methemoglobinemia; Middle Aged; NAD; Neomycin

Topics: Adult; Amino Acids; Anemia, Hemolytic; Ascorbic Acid; Cerebellar Diseases; Cyanides; Electroencephalography; Electromyography; Erythrocytes; Female; Glutathione; Humans; Leukocytes; Male; Metabolism, Inborn Errors; Muscles; Neural Conduction; Peptide Synthases; Potassium; Renal Aminoacidurias; Spinal Cord Diseases; Syndrome

Thyroxine (T(4)) and triiodothyronine (T(9)) are rapidly degraded by a purified preparation of myeloperoxidase (MPO) and H(2)O(2) with the formation of iodide and material which remains at the origin on paper chromatography. Deiodination by MPO and H(2)O(2) occurs more readily at pH 7.0 than at pH 5.0 in contrast to iodination by this system which is known to occur more readily at pH 5.0 than at pH 7.0. Degradation is inhibited by azide, cyanide, ascorbic acid, and propylthiouracil. Methimazole stimulates deiodination by MPO and H(2)O(2) but inhibits this reaction when MPO is replaced by lactoperoxidase or horseradish peroxidase.Intact human leukocytes, in the resting state, degrade T(4) and T(3) slowly: degradation, however, is increased markedly during phagocytosis of preopsonized particles. Serum inhibits this reaction. T(3) can be detected as a minor product of T(4) degradation. Proteolytic digestion of the reaction products increases the recovery of monoiodotyrosine. The fixation of iodine in the cytoplasm of leukocytes which contain ingested bacteria was detected radioautographically. Chronic granulomatous disease leukocytes, which are deficient in H(2)O(2) formation, degrade T(4) and T(3) poorly during phagocytosis. MPO-deficient leukocytes degrade the thyroid hormones at a slower rate than do normal leukocytes although considerable degradation is still observed. Azide, cyanide, ascorbic acid, and propylthiouracil which inhibit certain peroxidasecatalyzed reactions inhibit degradation by normal leukocytes; however, inhibition is incomplete. Formation of iodinated origin material is inhibited to a greater degree by azide, cyanide, and propylthiouracil than is deiodination. Methimazole inhibits the formation of iodinated origin material by both normal and MPO-deficient leukocytes. However, deiodination by normal leukocytes is stimulated and that of MPO-deficient leukocytes is unaffected by methimazole. Hypoxia inhibits the degradation of T(4) and T(3) by untreated normal or MPO-deficient leukocytes and by normal leukocytes treated with azide or methimazole. These data suggest that both MPO-dependent and MPO-independent systems are involved in the degradation of T(4) and T(3) by phagocytosing leukocytes. The role of leukocytic degradation of T(4) and T(3) in thyroid hormone economy and in leukocytic microbicidal activity is considered.

Topics: Ascorbic Acid; Azides; Chromatography, Gel; Chromatography, Paper; Cyanides; Electrophoresis, Paper; Humans; Hydrogen Peroxide; In Vitro Techniques; Iodine Isotopes; Lactobacillus acidophilus; Leukocytes; Metabolism, Inborn Errors; Methimazole; Oxygen; Peroxidases; Phagocyte Bactericidal Dysfunction; Phagocytosis; Propylthiouracil; Thyroid Hormones; Thyroxine; Triiodothyronine

Topics: Ascorbic Acid; Austria; Birth Weight; Humans; Infant, Newborn; Mass Screening; Metabolism, Inborn Errors; Tyrosine

Topics: Anemia, Hemolytic; Ascorbic Acid; Carbon Radioisotopes; Cell Survival; Chromium Radioisotopes; Erythrocytes; Glucose; Glucosephosphate Dehydrogenase Deficiency; Heinz Bodies; Hemolysis; Hexosephosphates; Humans; Metabolism, Inborn Errors; Primaquine; Renal Dialysis; Sulfonamides; Uremia; Water

Topics: Ascorbic Acid; Birth Weight; Breast Feeding; Gastroenteritis; Humans; Hypernatremia; Infant Food; Infant Nutrition Disorders; Infant Nutritional Physiological Phenomena; Infant, Newborn; Infant, Newborn, Diseases; Metabolism, Inborn Errors; Respiratory Tract Infections; Tetany; Vitamin A; Vitamin D; Vitamin K; Vomiting

Topics: Ascorbic Acid; Dihydrolipoamide Dehydrogenase; Female; Heterozygote; Humans; Infant, Newborn; Infant, Newborn, Diseases; Metabolism, Inborn Errors; Methemoglobinemia; Methylene Blue; Pedigree

Topics: Ascorbic Acid; Follow-Up Studies; Humans; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature, Diseases; Mass Screening; Metabolism, Inborn Errors; Tyrosine

Topics: Ascorbic Acid; Catecholamines; Epinephrine; Humans; Infant, Newborn; Infant, Premature, Diseases; Metabolism, Inborn Errors; Norepinephrine; Nutritional Requirements; Tyrosine; Vanilmandelic Acid

Topics: Adult; Ascorbic Acid; Blood Protein Electrophoresis; Clinical Enzyme Tests; Hematocrit; Hemoglobinometry; Humans; Male; Metabolism, Inborn Errors; Methemoglobin; Methemoglobinemia; Oxidoreductases; Spectrophotometry; Thailand

Topics: Ascorbic Acid; Chronic Disease; Dopamine; Humans; Metabolism, Inborn Errors; Methyldopa; Schizophrenia; Thalamus; Tyrosine

Topics: Adult; Ascorbic Acid; Autoimmune Diseases; Ceruloplasmin; Chronic Disease; Copper; Diet; Humans; Male; Mathematics; Metabolism, Inborn Errors; Middle Aged; Schizophrenia; Time Factors

The ability of several species of birds to synthesize L-ascorbic acid is correlated with their phylogeny. In the more primitive species, synthesis of L-ascorbic acid occurs in the kidney. Among the highly evolved passeriform species, kidney and liver can synthesize L-ascorbic acid in some, whereas in others synthesis occurs in the liver. In still others, the capacity for the synthesis of L-ascorbic acid is apparently lost. The pattern of evolution of the ascorbic acid pathway among birds is thus similar to that among mammals.

Topics: Animals; Ascorbic Acid; Biological Evolution; Birds; Kidney; Liver; Mammals; Metabolism, Inborn Errors; Microsomes; Oxidoreductases; Physiology, Comparative; Stereoisomerism

Topics: Ascorbic Acid; Body Weight; Child, Preschool; Diet Therapy; Humans; Intellectual Disability; Male; Metabolism, Inborn Errors; Nervous System Diseases; Obsessive-Compulsive Disorder; Pedigree; Self Mutilation; Uric Acid

Topics: Alcohol Oxidoreductases; Ascorbic Acid; Humans; Liver; Metabolism, Inborn Errors; Scurvy

Topics: Ascorbic Acid; Humans; Metabolism, Inborn Errors; Scurvy

Topics: Anemia; Anemia, Sickle Cell; Ascorbic Acid; Counseling; Eugenics; Galactosemias; Genetics, Medical; Humans; Immunity; Malaria; Metabolism, Inborn Errors; Phenylketonurias; Preventive Medicine

Topics: Acatalasia; Anemia; Anemia, Hemolytic; Ascorbic Acid; Azides; Catalase; Cyanides; Erythrocyte Aging; Erythrocytes; Ethylmaleimide; Genetics, Medical; Glucose; Glucosephosphate Dehydrogenase Deficiency; Glucosephosphates; Glutathione; Hemoglobins; Hemolysis; Hexosephosphates; Humans; Metabolism, Inborn Errors; Methemoglobin; Peroxides; Pharmacology; Phenylhydrazines; Primaquine; Sulfhemoglobin; Sulfhydryl Compounds

Topics: Ascorbic Acid; Child; Child, Preschool; Glycine; Glyoxylates; Humans; In Vitro Techniques; Metabolism, Inborn Errors; Oxalates; Urinary Calculi; Urine

Topics: Ascorbic Acid; Dihydrolipoamide Dehydrogenase; Drug Therapy; Erythrocytes; Humans; Metabolism, Inborn Errors; Methemoglobin; Methemoglobinemia; Methylene Blue; NAD; Sulfites; Vitamin K; Vitamin K 3