Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two brothers with Progressive myoclonic epilepsy and Juvenile bulbar and spinal atrophy had clinical, neurophysiological study and muscle biopsy. The EEG and polygraphic findings included progressive slowing of the background activity, spontaneous fast generalised spike- and wave discharges and photosensitivity. The EMG revealed pathological spontaneous activity as well as motor unit potentials diminished in number and increased in amplitude and duration; while VDCS and VDCM were normal. Results of muscle biopsy showed no represented "ragged red fibers" with the modified Trichrome stain, while grouped small caliber angular fibers of both histochemical type were visible with the myofibrillar ATPase reaction, but type 2 fibers predominated amongst the atrophic ones. Serum and urine metabolic measurement and lysosomal enzyme activities in leukocytes were all normal. We feel that the reported case might represent a familial syndrome not previously recognized showing non-specific degenerative changes with neuropathological examination. This disorder is similar only to the case reported by Lance J.W. and Ewans W.A. in 1984 "Progressive myoclonic epilepsy, nerve deafness and muscular atrophy".
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PMID:[Progressive familial myoclonic epilepsy with bulbo-spinal amyotrophy. Clinical, electrophysiological study, and biopsy of a case]. 215 3

The influences of iron deficiency on the cochlear iron enzymes and adenosine triphosphatase were studied in 68 iron-deficient rats and 68 control rats (normal and with chronic anemia). A disorderly or topographic distribution and reduction or disappearance of the cochlear succinic dehydrogenase and peroxidase reaction products were found in 37.8% of the rats fed on a basic iron-deficient diet for 14 to 100 days. The activity of cochlear sodium-potassium-dependent adenosine triphosphatase in iron-deficient rats was slightly increased, compared to that in normal controls. These results suggest that iron deficiency would produce significant abnormalities of succinic dehydrogenase and peroxidase activity, which in turn would disturb cell respiration and initiate peroxidative damage to the inner ear cells, result in sensorineural hearing loss, or provide a pathologic basis for cochlear deafness.
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PMID:Changes in the cochlear iron enzymes and adenosine triphosphatase in experimental iron deficiency. 217 94

Thirty patients with functional and/or morphological abnormalities of respiratory tract cilia were identified. The diagnosis of primary ciliary dyskinesia was based on observed abnormalities of ciliary ultrastructure or beating in vitro (beat pattern, beat frequency or percentage of motile cilia). Beat frequency and motility indices approached the normal range in some cases and suggests that the term 'immotile cilia syndrome' is not appropriate. Morphological abnormalities were most commonly due to deficiency of dynein arms, affecting the outer arms (n = 7), inner arms (n = 3) or both (n = 10). Examples of radial spoke and microtubular defects were also identified but in seven subjects ciliary ultrastructure was normal. In six patients paired samples of nasal and bronchial cilia were obtained and showed consistent abnormalities of motility and ultrastructure. Adenosine triphosphate and adenosine triphosphatase did not restore in vitro motility when added to dynein deficient cilia. The clinical picture was of life-long sinusitis and recurrent bronchial infection but the spectrum was broader than that encompassed by Kartagener's triad (dextrocardia, sinusitis and bronchiectasis). Fourteen patients had normal cardiac situs and definite or highly suggestive evidence of bronchiectasis was present in only 17 patients. Radiological evidence of sinusitis was common but absence of frontal sinuses was not universal. Chronic serous otitis media was a frequent finding but deafness was rarely profound. Fertility problems were common but were not universal in female subjects. Lung function testing revealed evidence of airflow obstruction but this was mild in most cases.
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PMID:Primary ciliary dyskinesia: cytological and clinical features. 297 7

Mice homozygous for mutations at the viable dominant spotting (Wv) and Steel-dickie (Sld) loci exhibit a similar phenotype which includes deafness. The auditory dysfunction derives from failure of the stria vascularis to develop normally and to generate a high positive endocochlear potential (EP). Because strial function is driven by Na,K-ATPase its expression was investigated in inner ears of Wv/Wv and Sld/Sld mice and their wild-type littermates by immunostaining with antisera against four of the enzyme's subunit isoforms. Wild-type mice from two different genetic backgrounds showed an identical distribution of subunit isoforms among inner ear transport cells. Several epithelial cell types coexpressed the alpha 1 and beta 1 subunits. Vestibular dark cells showed no reactivity for beta 1 but expressed abundant beta 2, whereas, strial marginal cells stained strongly for both beta isoforms. The only qualitative difference between mutant and wild-type mice was the absence of beta 1 subunit in marginal cells of the mutant's stria. However, it is unlikely that this difference accounts for failure of mutants to generate a high EP because the beta 1 subunit is not present in the stria vascularis of either rats or gerbils with normal EP values. Strong immunostaining for Na,K-ATPase in lateral wall fibrocytes of normal mice along with diminished immunoreactivity in the mutants supports the concept that these strategically located transport fibrocytes actively resorb K+ leaked across Reissner's membrane into scala vestibuli or effluxed from hair cells and nerves into scala tympani. It is further speculated that the resorbed K+ normally is siphoned down its concentration gradient into the intrastrial space through gap junctions between fibrocytes and strial basal and intermediate cells where it is recycled back to endolymph via marginal cells. Thus, failure of mutants to generate a positive EP could be explained by the absence of intermediate cells which may form the final link in the conduit for moving K+ from perilymph to the intrastrial compartment.
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PMID:Expression of alpha and beta subunit isoforms of Na,K-ATPase in the mouse inner ear and changes with mutations at the Wv or Sld loci. 796 Nov 79

The Drosophila melanogaster white gene is a member of the ABC transporter superfamily of ATPase transmembrane proteins and is involved in the cellular uptake of guanine and tryptophan. We have cloned and sequenced human and mouse homologs of white which share 55-58% amino acid similarity with the Drosophila protein. Northern analysis reveals that the mammalian homolog is highly expressed in several tissues, including brain, spleen, lung and placenta. We have localized the gene to human chromosome 21q22.3 by means of fluorescence in situ hybridization and linkage analysis using a (CA)n polymorphism. The human homolog maps to the interval between D21S212 and D21S171, a region which includes loci for bipolar affective disorder and a recessive form of deafness. Since tryptophan is a precursor for the neurotransmitter serotonin and neurotoxic metabolites of the kynurenine pathway, we propose that the human homolog of white is a suitable candidate gene for these neurological disorders in humans.
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PMID:Isolation and characterization of a mammalian homolog of the Drosophila white gene. 903 16

The multi-subunit H+-ATPase pump is present at particularly high density on the apical (luminal) surface of -intercalated cells of the cortical collecting duct of the distal nephron, where vectorial proton transport is required for urinary acidification. The complete subunit composition of the apical ATPase, however, has not been fully agreed upon. Functional failure of -intercalated cells results in a group of disorders, the distal renal tubular acidoses (dRTA), whose features include metabolic acidosis accompanied by disturbances of potassium balance, urinary calcium solubility, bone physiology and growth. Mutations in the gene encoding the B-subunit of the apical pump (ATP6B1) cause dRTA accompanied by deafness. We previously localized a gene for dRTA with preserved hearing to 7q33-34 (ref. 4). We report here the identification of this gene, ATP6N1B, which encodes an 840 amino acid novel kidney-specific isoform of ATP6N1A, the 116-kD non-catalytic accessory subunit of the proton pump. Northern-blot analysis demonstrated ATP6N1B expression in kidney but not other main organs. Immunofluorescence studies in human kidney cortex revealed that ATP6N1B localizes almost exclusively to the apical surface of -intercalated cells. We screened nine dRTA kindreds with normal audiometry that linked to the ATP6N1B locus, and identified different homozygous mutations in ATP6N1B in eight. These include nonsense, deletion and splice-site changes, all of which will truncate the protein. Our findings identify a new kidney-specific proton pump 116-kD accessory subunit that is highly expressed in proton-secreting cells in the distal nephron, and illustrate its essential role in normal vectorial acid transport into the urine by the kidney.
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PMID:Mutations in ATP6N1B, encoding a new kidney vacuolar proton pump 116-kD subunit, cause recessive distal renal tubular acidosis with preserved hearing. 1097 52

The diagnosis and classification of renal tubular acidosis (RTA) have traditionally been made on the basis of functional studies. On these grounds, RTA has been separated into three main categories: (1) proximal RTA, or type 2; (2) distal RTA, or type 1; and (3) hyperkalemic RTA, or type 4. In recent years significant advances have been made in our understanding of the subcellular mechanisms involved in renal bicarbonate (HCO3-) and H+ transport. Application of molecular biology techniques has also opened a completely new perspective to the understanding of the pathophysiology of inherited cases of RTA. Mutations in the gene SLC4A4, encoding Na+-HCO3- cotransporter (NBC-1), have been found in proximal RTA with ocular abnormalities; in the gene SLC4A1, encoding Cl(-)-HCO3- exchanger (AE1), in autosomal dominant distal RTA; in the gene ATP6B1, encoding B1 subunit of H+-ATPase, in autosomal recessive distal RTA with sensorineural deafness; and in the gene CA2, encoding carbonic anhydrase II, in autosomal recessive osteopetrosis. Syndromes of aldosterone resistance have been also characterized molecularly and mutations in the gene MLR, encoding mineralocorticoid receptor, and in the genes SNCC1A, SNCC1B, and SCNN1G, encoding subunits of the epithelial Na+ channel, have been found in dominant and recessive forms of pseudohypoaldosteronism type 1, respectively. It can be concluded that, although functional studies are still necessary, a new molecular era in the understanding of disorders of renal acidification has arrived.
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PMID:New insights into the pathogenesis of renal tubular acidosis--from functional to molecular studies. 1104

The primary or hereditary form of distal renal tubular acidosis (dRTA), although rare, has received increased attention recently because of dramatic advances in the understanding of its genetic basis. The final regulation of renal acid excretion is effected by various acid/base transporters localized in specialized cells in the cortical collecting and outer medullary collecting tubules. Inherited defects in two of the key acid/base transporters involved in distal acidification, as well as mutations in the cytosolic carbonic anhydrase gene, can cause dRTA. The syndrome is inherited in both autosomal dominant and recessive patterns; patients with recessive dRTA present with either acute illness or growth failure at a young age, sometimes accompanied by deafness, whereas dominant dRTA is usually a milder disease and involves no hearing loss. The AE1 gene encodes two Cl-/HCO3- exchangers that are expressed in the erythrocyte and in the acid-secreting intercalated cells of the kidney. AE1 contributes to urinary acidification by providing the major exit route for HCO3- across the basolateral membrane. Several mutations in the AE1 gene cosegregate with dominant dRTA. The modest degree of hypofunction exhibited in vitro by these mutations, however, does not explain the abnormal distal acidification phenotype. Other AE1 mutations have been linked to a recessive syndrome of dRTA and hemolytic anemia in which hypofunction can be discerned by in vitro studies. Several mutations in the carbonic anyhdrase II gene are associated with the autosomal recessive syndrome of osteopetrosis, renal tubular acidosis, and cerebral calcification. Some of these individuals present with deafness of the conductive type. By contrast, more recent studies have shown that mutations in ATP6B1, encoding the B-subtype unit of the apical H(+) ATPase, are responsible for a group of patients with autosomal recessive dRTA associated with sensorineural deafness. Thus, the presence of deafness and the type provide an important clue to the genetic lesion underlying hereditary dRTA.
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PMID:Hereditary distal renal tubular acidosis: new understandings. 1116 Jul 90

Pendrin is an anion transporter encoded by the PDS/Pds gene. In humans, mutations in PDS cause the genetic disorder Pendred syndrome, which is associated with deafness and goiter. Previous studies have shown that this gene has a relatively restricted pattern of expression, with PDS/Pds mRNA detected only in the thyroid, inner ear, and kidney. The present study examined the distribution and function of pendrin in the mammalian kidney. Immunolocalization studies were performed using anti-pendrin polyclonal and monoclonal antibodies. Labeling was detected on the apical surface of a subpopulation of cells within the cortical collecting ducts (CCDs) that also express the H(+)-ATPase but not aquaporin-2, indicating that pendrin is present in intercalated cells of the CCD. Furthermore, pendrin was detected exclusively within the subpopulation of intercalated cells that express the H(+)-ATPase but not the anion exchanger 1 (AE1) and that are thought to mediate bicarbonate secretion. The same distribution of pendrin was observed in mouse, rat, and human kidney. However, pendrin was not detected in kidneys from a Pds-knockout mouse. Perfused CCD tubules isolated from alkali-loaded wild-type mice secreted bicarbonate, whereas tubules from alkali-loaded Pds-knockout mice failed to secrete bicarbonate. Together, these studies indicate that pendrin is an apical anion transporter in intercalated cells of CCDs and has an essential role in renal bicarbonate secretion.
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PMID:Pendrin, encoded by the Pendred syndrome gene, resides in the apical region of renal intercalated cells and mediates bicarbonate secretion. 1127 45

Neuropathy, ataxia, and retinitis pigmentosa (NARP) syndrome and maternally inherited Leigh's syndrome have been associated with T8993G point mutations in the mitochondrial adenosine triphosphatase 6 gene. Typically, NARP syndrome is characterized by developmental delay, seizures, dementia, retinitis pigmentosa, ataxia, sensory neuropathy, and proximal weakness. Usually, there is a correlation between the percentage of mutated mitochondrial DNA and clinical severity, and when mutated mitochondrial DNA is > 90%, it is often seen with Leigh's syndrome. We now report a family with mitochondrial DNA T8993G mutation in eight living members, five with mutant mitochondrial DNA >90% and one with 20% mutant mitochondrial DNA. However, their clinical features include variable combinations of seizures, behavior problems, learning disability, mental retardation, sensorineural deafness, cerebellar ataxia, and proximal muscle weakness. No retinitis pigmentosa was found in all eight living members, including a 56-year-old grandmother. Only one dead female relative was diagnosed with Leigh's syndrome on the neuropathologic examination at age 22 years, when she died of an accident. High mitochondrial DNA T8993G mutation is not always associated with typical features of Leigh's and NARP syndromes.
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PMID:High mitochondrial DNA T8993G mutation (<90%) without typical features of Leigh's and NARP syndromes. 1145 54


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