RESUMEN
The periplasmic reduction of the electron acceptors nitrate (Em +420 mV) and trimethylamine-N-oxide (TMAO; Em +130 mV) by Nap and Tor reductases is widespread in Gram-negative bacteria and is usually considered to be driven by non-energy conserving quinol dehydrogenases. The Epsilonproteobacterium Campylobacter jejuni can grow by nitrate and TMAO respiration and it has previously been assumed that these alternative pathways of electron transport are independent of the proton-motive menaquinol-cytochrome c reductase complex (QcrABC) that functions in oxygen-linked respiration. Here, we show that a qcrABC deletion mutant is completely deficient in oxygen-limited growth on both nitrate and TMAO and is unable to reduce these oxidants with physiological electron donors. As expected, the mutant grows normally on fumarate under oxygen-limited conditions. Thus, the periplasmic Nap and Tor reductases receive their electrons via QcrABC in C. jejuni, explaining the general absence of NapC and TorC quinol dehydrogenases in Epsilonproteobacteria. Moreover, the specific use of menaquinol (Em -75 mV) coupled with a Qcr complex to drive reduction of nitrate or TMAO against the proton-motive force allows the process to be electrogenic with a H+/2e- ratio of 2. The results have general implications for the role of Qcr complexes in bacterial oxygen-independent respiration and growth.
Asunto(s)
Campylobacter jejuni/enzimología , Campylobacter jejuni/metabolismo , Reductasas del Citocromo/metabolismo , Transporte de Electrón , Metilaminas/metabolismo , Nitratos/metabolismo , Campylobacter jejuni/crecimiento & desarrollo , Reductasas del Citocromo/deficiencia , Eliminación de Gen , Oxidación-ReducciónRESUMEN
A 17-year-old patient had a progressive hypokinetic-rigid syndrome and several other signs and symptoms that indicated central nervous system involvement. Biochemical studies revealed a reduced form of nicotinamide-adenine dinucleotide dehydrogenase deficiency in skeletal muscle. Clinical signs and symptoms, and their association with an established defect of energy metabolism, led us to classify this disorder as a mitochondrial encephalomyopathy of Leigh's type.
Asunto(s)
Encefalopatías Metabólicas/enzimología , Reductasas del Citocromo/deficiencia , Enfermedad de Leigh/enzimología , Mitocondrias Musculares/enzimología , Enfermedades Musculares/enzimología , NADH Deshidrogenasa/deficiencia , Adolescente , Metabolismo Energético , Humanos , Enfermedad de Leigh/fisiopatología , Masculino , Enfermedades Musculares/fisiopatologíaRESUMEN
A 37-yr-old woman with nontoxic goiter is presented. The thyroid 131I uptake at 3 and 24 hr were, respectively, 77.1% and 81.4% dose. Thiocyanate discharged 65.5% of the accumulated 131I in 30 min. In vitro organification of iodine in the thyroid homogenate from the patient was impaired and it was restored to normal by the addition of H2O2, glucose, and glucose oxidase system, FAD, or reduced cytochrome b5. Riboflavin, FMN, oxidized cytochrome b5, oxidized or reduced cytochrome c, NAD(H), and NADP(H) were ineffective in the reaction. The microsomal NADH-cytochrome b5 reductase activity was definitely low in the patient's thyroid. It was augmented to a normal level by incubation of the microsomes with FAD for 30 min or more. The activities of thyroid peroxidase, G6-PD, 6-PGD, catalase, protease, and NADPH-cytochrome c reductase were within normal limits. The major thyroid protein was normal thyroglobulin which could be readily iodinated in the presence of H2O2 and horse radish peroxidase. These findings suggest the correlation of an iodide organification defect with a cytochrome b5 reductase deficiency. Administration of high doses of FAD led to the restoration of thyroidal iodide organification mechanism associated with an increased thyroid hormone production and to a marked decrease of the goiter. Riboflavin was given without effect even at a high dosage level. Consequently, it seems likely that the deficient cytochrome b5 reductase activity in this patient is due to a defect in the biosynthesis of FAD, the coenzyme of the reductase, from riboflavin.
Asunto(s)
Reductasas del Citocromo/deficiencia , Bocio/enzimología , Yodo/metabolismo , Adulto , Catalasa/metabolismo , Femenino , Flavina-Adenina Dinucleótido/biosíntesis , Flavina-Adenina Dinucleótido/uso terapéutico , Glucosafosfato Deshidrogenasa/metabolismo , Bocio/tratamiento farmacológico , Bocio/etiología , Humanos , Microsomas/enzimología , Péptido Hidrolasas/metabolismo , Peroxidasas/metabolismo , Fosfogluconato Deshidrogenasa/metabolismo , Riboflavina/metabolismo , Tiroglobulina/metabolismo , Glándula Tiroides/enzimologíaRESUMEN
This paper presents biochemical data upon a young male with a mitochondrial myopathy characterised by weakness, severe exercise intolerance, muscle wasting and exercise-induced lactic acidaemia. Two similar cases have been previously documented (Morgan-Hughes et al. 1979). This report more precisely locates the mitochondrial defect. In vitro mitochondrial studies show markedly decreased respiratory rates with all NAD-linked substrates whilst that with flavin-linked succinate is normal. Oxidative phosphorylation is normally coupled. Mitochondrial cytochrome components as determined by low temperature spectroscopy are normal. NADH-ferricyanide reductase and primary dehydrogenase activities are present at levels far in excess of that required to support normal NAD-linked substrate oxidation rates. Intramitochondrial NAD levels are similar to those found in other mammalian muscle. It is proposed therefore that the mitochondrial defect is situated between NADH dehydrogenase and the CoQ--Cytochrome b complex; possibly being a derangement of a non-haem iron sulphur centre.
Asunto(s)
Reductasas del Citocromo/deficiencia , Mitocondrias Musculares/enzimología , Atrofia Muscular/enzimología , NADH Deshidrogenasa/deficiencia , Enfermedades Neuromusculares/enzimología , Adulto , Humanos , Lactatos/sangre , Masculino , NAD/metabolismo , Esfuerzo FísicoRESUMEN
This paper presents data on two sisters with a mitochondrial myopathy characterised by weakness, marked exercise intolerance and a fluctuating lactic acidaemia. Both patients also experienced episodes of increased weakness which could be brought on by unaccustomed activity, going without food or by taking small quantities of alcohol. Metabolic studies during exercise showed a marked and sudden rise in blood lactate and pyruvate levels. Biochemical studies in one case showed that mitochondrial respiratory rates were markedly decreased with all NAD-linked substrates tested but were normal with succinate and with TMPD + ascorbate. The mitochondrial cytochrome components were normal as determined by low temperature spectroscopy and the addition of uncoupler did not enhance state 3 respiratory rates utilising NAD-linked substrates. It was concluded, therefore, that the mitochondrial lesion was located at the level of the NADH-CoQ reductase complex.
Asunto(s)
Reductasas del Citocromo/deficiencia , Mitocondrias Musculares/enzimología , Enfermedades Musculares/enzimología , NADH NADPH Oxidorreductasas/deficiencia , Quinona Reductasas/deficiencia , Adulto , Fenómenos Químicos , Química , Transporte de Electrón , Femenino , Humanos , Mitocondrias Musculares/ultraestructura , Enfermedades Musculares/genética , Enfermedades Musculares/patología , Esfuerzo Físico , UbiquinonaRESUMEN
Two siblings with succinic acidemia, a hitherto unreported organic acidemia, were investigated. Succinic acidemia, lactic acidosis and respiratory distress were observed in one of the siblings, who died 37 days after birth, and succinic acidemia was also detected in the next sibling at the fetal stage. NADH-cytochrome c reductase activity was significantly low in both cases and NADH-ferricyanide reductase activity was also low in the fetal case, suggesting a complex I deficiency of the electron transport system in the mitochondrial membrane.
Asunto(s)
Acidosis Láctica/congénito , Reductasas del Citocromo/deficiencia , NADH Deshidrogenasa/deficiencia , Succinatos/sangre , Acidosis Láctica/enzimología , Acidosis Láctica/metabolismo , Líquido Amniótico/análisis , Transporte de Electrón , Femenino , Enfermedades Fetales/enzimología , Humanos , Recién Nacido , Mitocondrias Hepáticas/análisis , Embarazo , Ácido SuccínicoRESUMEN
The lipid compositions of liver, kidney, spleen and muscle in a case of generalized deficiency of cytochrome b5 reductase in congenital methemoglobinemia with mental retardation were analyzed and compared with age-matched controls. The contents of cholesterol and phospholipids (mumol/g) in each organ were within the normal range. Diminished proportions of unsaturated fatty acids were observed in ethanolamine phosphoglycerides (EPG) of the liver. The proportion of linoleic acid decreased to less than half of the normal level in EPG of liver, kidney and spleen.
Asunto(s)
Reductasas del Citocromo/deficiencia , Discapacidad Intelectual/complicaciones , Lípidos/análisis , Metahemoglobinemia/metabolismo , Citocromo-B(5) Reductasa , Ácidos Grasos/análisis , Humanos , Riñón/análisis , Hígado/análisis , Metahemoglobinemia/complicaciones , Músculos/análisis , Bazo/análisisRESUMEN
The lipid classes and fatty acid compositions of myelin, white matter and gray matter were analyzed in a case of generalized deficiency of cytochrome b5 reductase in congenital methemoglobinemia with mental retardation. When compared with normal data, the percentage of 24:1 was considerably decreased and diminished unsaturation was observed in cerebrosides, whereas the sum of 24:0 and 24:1 was the same as in normals. The ratio of hydroxy fatty acids to total fatty acids in cerebrosides was low. The contents of cholesterol and phospholipids in white matter were reduced to 80% of the normal, whereas cerebroside was reduced to 48% of the normal.
Asunto(s)
Química Encefálica , Reductasas del Citocromo/deficiencia , Discapacidad Intelectual/metabolismo , Lípidos/análisis , Metahemoglobinemia/metabolismo , Vaina de Mielina/análisis , Cerebrósidos/análisis , Niño , Preescolar , Colesterol/análisis , Citocromo-B(5) Reductasa , Femenino , Humanos , Masculino , Fosfolípidos/análisis , Valores de Referencia , Ácidos Siálicos/análisis , Esfingolípidos/análisisRESUMEN
A patient with cyanosis due to methaemoglobinaemia caused by cytochrome b5 reductase deficiency is described. Investigation of his family confirmed transmission of this disorder as an autosomal recessive trait. The consequences of this rare condition are discussed.
Asunto(s)
Cianosis/etiología , Reductasas del Citocromo/deficiencia , Anciano , Cianosis/enzimología , Citocromo-B(5) Reductasa , Humanos , Masculino , LinajeRESUMEN
Continuing progress has been made in the exploration of the biochemical causes of mental illness. Recent research has indicated that selected abnormalities of specific isoenzymes play an important role in the pathogenesis of heritable metabolic disorders such as phenylketonuria and Niemann-Pick disease. The roles of "animal lectins" and glycosidic enzymes in brain development and synaptogenesis appear to have received important substantiation within the past year. In additions, it has been shown that the blood-brain barrier can be temporarily altered so that exogenous enzymes can enter the central nervous system, and imperative consideration for enzyme replacement therapy in mental disorders. Less satisfactory progress has been made concerining potential anabolic disorders of lipids affecting the nervous system. Finally, novel experimental directions concerning energy metabolism by the brain offer considerable hope for the elucidation of some of the causes of mental retardation.
Asunto(s)
Discapacidad Intelectual/metabolismo , Errores Innatos del Metabolismo/metabolismo , Errores Innatos del Metabolismo de los Aminoácidos/metabolismo , Animales , Encéfalo/metabolismo , Errores Innatos del Metabolismo de los Carbohidratos/metabolismo , Reductasas del Citocromo/deficiencia , Desoxiglucosa/metabolismo , Dihidrolipoamida Deshidrogenasa/deficiencia , Metabolismo Energético , Gangliósidos/metabolismo , Humanos , Discapacidad Intelectual/etiología , Errores Innatos del Metabolismo Lipídico/metabolismo , Errores Innatos del Metabolismo/complicaciones , Fenilalanina/metabolismo , Enfermedad por Deficiencia del Complejo Piruvato DeshidrogenasaRESUMEN
Individuals with methemoglobin exceeding 1.5 g/dl have clinically obvious central cyanosis. Hereditary methemoglobinemia is due either to autosomal dominant M hemoglobins or to autosomal recessive enzymopenic methemoglobinemia. Four types of enzymopenic methemoglobinemia have been described. In addition to methemoglobinemia, individuals with type II, which is the generalized cytochrome b5 reductase deficiency, have severe and progressive neurological disabilities. Here we report a 3-year-old Thai boy with type II hereditary enzymopenic methemoglobinemia. He was born to a second-cousin couple. His central cyanosis was first observed around 10 months of age. His neurological abnormalities were seizures beginning at 1 year of age, microcephaly, and inability to hold his head up. His cardiovascular and pulmonary evaluations were unremarkable. Methemoglobin level by spectral absorption pattern was 18 per cent. A qualitative enzymatic assay confirmed the deficiency of the cytochrome b5 reductase enzyme. With this definite diagnosis, a prenatal diagnosis for the next child of this couple will be possible.
Asunto(s)
Reductasas del Citocromo/deficiencia , Metahemoglobinemia/diagnóstico , Preescolar , Citocromo-B(5) Reductasa , Hemoglobinas/fisiología , Humanos , Masculino , Metahemoglobina/metabolismo , Metahemoglobinemia/genética , Metahemoglobinemia/terapia , Azul de Metileno/uso terapéutico , Oxígeno/metabolismo , Linaje , Índice de Severidad de la Enfermedad , TailandiaRESUMEN
Autosomal recessive hereditary methemoglobinemia associated with mental retardation is a rare syndrome caused by a deficiency of the enzyme NADH cytochrome b5 reductase. A patient suffering from this disorder is described. The etiology of the syndrome and the (im)possibilities of treatment and prenatal diagnosis are discussed.