Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eleven patients with porphyria cutanea tarda were studied. Biochemical confirmation of the clinical diagnosis required only determination of the total urine porphyrin concentration in a sample of urine voided on rising in the morning. The patients were divided for convenience of discussion into four groups differing in age, sex and etiologic factors. Of the six patients in whom a liver biopsy was done one was shown to have micronodular cirrhosis. Except for a modest elevation in the serum glutamic oxaloacetic transaminase values when the patients were first seen, no evidence was found for liver disease apart from the presence of porphyria cutanea tarda. One patient recovered solely by abstaining from alcohol consumption. Five patients underwent phlebotomy; their iron stores had been found to be between 2 and 3 g. Decreasing urine porphyrin values correlated well with decreasing serum ferritin values during the course of phlebotomy. Porphyria cutanea tarda, which is due to a deficiency of uroporphyrinogen decarboxylase, is manifested in association with alcohol abuse, estrogen therapy, exposure to chlorinated hydrocarbons or increased tissue iron stores, or a combination of these factors. Although relatively uncommon, this condition raises important and unresolved issues regarding the hepatotoxicity of alcohol, estrogens, chlorinated hydrocarbons and iron.
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PMID:Porphyria cutanea tarda: clinical and laboratory features. 42 87

Porphyria cutanea tarda (PCT) and experimental porphyria are characterized by a decreased activity of the enzyme uroporphyrinogen decarboxylase, and accumulation of uroporphyrins and heptacarboxylporphyrins in the liver. Iron (Fe) plays an important role in PCT and experimental porphyria. Biochemically and electron microscopically, we examined the relationship between Fe and porphyrins in liver tissue of C57BL/10 mice made porphyric by administration of iron dextran as Imferon (IMF), and in liver biopsies of patients with symptomatic PCT. Accumulation of uroporphyrins and heptacarboxylporphyrins, and an increased amount of Fe were observed in livers of mice treated with IMF and in liver biopsies of patients with PCT. In mice treated with IMF, the activity of uroporphyrinogen decarboxylase was decreased. Both in livers of mice treated with IMF and in livers of patients with PCT, needle-like structures, representing uroporphyrin crystals, were observed by electron microscopy. Uroporphyrin crystals and Fe (as ferritin) were observed in the same hepatocyte. Moreover, there was a striking morphological correlation between uroporphyrin crystals and ferritin-Fe, suggesting a role for (ferritin-)Fe in the pathogenesis of porphyria.
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PMID:The role of iron in experimental porphyria and porphyria cutanea tarda. 138 28

Sideroblastic anemia is an extremely rare disorder in children. This report describes a 9-year 4-month-old girl with severe refractory anemia with ringed sideroblasts (RARS) that progressed to severe bone marrow aplasia. Ultrastructural studies revealed the presence of abundant intramitochondrial deposits of iron in erythroblasts similar to that observed in adults with this disorder. Although acid ferrocyanide staining confirmed the ferric valence of the iron deposits, they lacked morphologic and cytochemical characteristics associated with ferritin and hemosiderin. Bone marrow culture showed decreased or absent CFU-GEMM, CFU-GM, CFU-E, and BFU-E. Erythrocyte uroporphyrinogen I synthase, aminolevulinic acid dehydratase, uroporphyrinogen decarboxylase, urinary porphyrins, porphobilinogen, and aminolevulinic acid were normal. Free red cell protoporphyrin was increased. Therapy with corticosteroid and androgens was totally ineffective. The aplastic bone marrow in this child appeared to represent the end stage of RARS and differed from adults with RARS, who more frequently demonstrate a chronic course, often with the onset of leukemia as a terminal sequela. Although this case documents the occurrence of RARS in a child, additional reports of children with this disorder will be required to determine the prognosis and natural history of RARS in children.
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PMID:Severe refractory anemia with ringed sideroblasts and bone marrow aplasia in a child. 155 Feb 66

Studies were carried out to elucidate if in the hexachlorobenzene (HCB) porphyria, total, nonhaem and haem iron contents in liver are altered and if any relation exists between these alterations and the hepatic porphyrinogen carboxy-lyase (PCL) decrease in rats treated with the drug. It was observed that in porphyric livers total and non-haem iron levels increased significantly as a consequence of HCB intoxication while this treatment produced a non significant decrease in the haem iron content. Enzymic preparations of porphyric livers filtered through Sephadex G-25 columns which separate the free iron and that has a content of iron-protein greater than those in normals, exhibited a strong inhibition of PCL. Chelating agents, alpha' alpha' bipyridyl and 8-hydroxyquinoline do not revert such inhibition. The effect in vitro of ferritin, haemin and inorganic iron at different concentrations on normal PCL activity was also assayed. So, it could be observed that inorganic iron and haemin produce slight inhibition of PCL when added in concentrations higher than those corresponding to a porphyric liver (0.08 mM and 10(-6) M, respectively, as mean in the incubation media). So, they have not physiological significance. Ferritin does not modify the decarboxylation process. From these results it arises that iron does not play a direct role in the decrease of PCL activity in the experimental porphyria by HCB, not being the inhibitor made evident by heating assays. Iron could perhaps stimulate the metabolization of HCB, giving rise to active metabolite.
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PMID:The role of iron in the hexachlorobenzene induced porphyria. I. Studies on different types of iron and its relation with porphyrinogen carboxy-lyase decrease. 294 Aug 9

The hypothesis that the accumulation of uroporphyrin, characteristic of uroporphyria, arises at least in part from oxidation of uroporphyrinogen and the molecular basis for the potentiation of the disorder by iron have been investigated. The iron chelates of ethylenediaminetetraacetic acid (EDTA) and nitrilotriacetic acid were very active at promoting the hydrogen peroxide-dependent oxidation of porphyrinogens, and a similar role of iron was found for the NADPH-dependent oxidation of porphyrinogens by liver microsomes in vitro. In contrast, neither the iron chelate of desferrioxamine (DES) nor ferritin iron possessed prooxidant activity, but the latter could be mobilized in an active form by incubation with EDTA. Iron was also found to promote further modification of the porphyrin pigment, leading to marked loss of its Soret absorbance. This latter effect, which could also be inhibited by DES, suggested further oxidative conversion of the accumulating uroporphyrin, but further work is necessary to establish the relevance of this (or similar) reaction to the inhibitor of uroporphyrinogen decarboxylase which has recently been reported. These results suggest a possible mechanism for the exacerbation of uroporphyria by excess iron and also for its marked improvement when the iron stores are diminished, for example, by DES treatment.
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PMID:Role of iron in the hydrogen peroxide-dependent oxidation of hexahydroporphyrins (porphyrinogens): a possible mechanism for the exacerbation by iron of hepatic uroporphyria. 312 28

This study was designed to determine whether iron contents are altered in hexachlorobenzene (HCB)-induced porphyria, and whether there is any relation between these alterations and the effects of the drug on several enzymes of the haem pathway. To this end, the effect of HCB administration on total, non-haem and haem iron levels was studied. Further, the effects of the addition of: both heated and non-heated HCB-porphyric liver preparations, iron as sulfate, ferritin and haemin and alpha alpha'-bipyridyl and 8-hydroxyquinoline were studied on the following enzymes: delta-aminolaevulinic acid synthase, delta-aminolaevulinic acid dehydratase, porphobilinogenase and porphyrinogen carboxy-lyase. Total and non-haem iron levels increased significantly as a result of HCB intoxication, but there was a non-significant decrease in haem iron content. The increased iron levels did not appear to be directly involved in the increased activities of delta-aminolaevulinic acid synthase and delta-aminolaevulinic acid dehydratase observed in HCB-induced porphyria, since it was not possible to detect any activation in heating and crossed assays nor by the addition of inorganic iron, protein-iron or haemin. Results from heating and crossed assays suggested the existence of an activator for porphobilinogenase and an inhibitor for porphyrinogen carboxy-lyase, while results obtained with chelating agents suggested that iron could partly account for the activation of porphobilinogenase. Iron was not directly involved with the decreased activity of porphyrinogen carboxy-lyase, since neither iron chelators nor different types of iron produced physiologically significant effects.
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PMID:Studies on the role of iron in the alterations observed in hexachlorobenzene-induced porphyria. 359 48

The review describes the structural and biochemical properties of the haem biosynthetic enzyme, uroporphyrinogen decarboxylase (UROD), which sequentially catalyzes the removal of the four carboxyl groups from the acetate side chains of octacarboxylic uroporphyrinogen to form coproporphyrinogen, and the possible biochemical mechanism of the genesis of porphyria cutanea tarda (PCT). The disease is caused when the activity of UROD is significantly reduced. PCT is a multifactorial disease where both inherent and environmental factors such as alcohol, estrogens, halogenated aromatic hydrocarbons and viral infection (mainly hepatitis C) are involved in biochemical and clinical expression. In PCT, hepatic iron plays a key role. Alcohol intake could induce mobilization of iron from protein-bound ferritin. PCT should be managed by avoidance of these toxins and removal of iron by vigorous phlebotomy. Such iron-reduction therapy would provide additional benefit for hepatitis C patients by interferon therapy.
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PMID:Haem biosynthesis and human porphyria cutanea tarda: effects of alcohol intake. 1121 4

Haemochromatosis is a hereditary iron-overload syndrome caused by increased intestinal iron absorption and characterised by accumulation of potentially toxic iron in the tissues. Sometimes this disease presents as a cutanea porphyria. We describe a patient with joint complaints and blistering skin lesions on sun-exposed skin. After identifying the porphyria cutanea tarda by urine analysis we found that the serum activity of uroporphyrinogen decarboxylase (UROD) was normal, meaning a partial inactivation of UROD in liver tissue due to external factors. Further investigation showed the homozygous Cys282Tyr missense mutation and high levels of serum ferritin. It is important to recognise the symptoms of iron overloading at an early stage because hereditary haemochromatosis needs to be treated immediately. We therefore advocate routine sampling of ferritin levels in patients with unexplained joint complaints.
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PMID:Sporadic porphyria cutanea tarda due to haemochromatosis. 1699 Jun 95

Porphyria cutanea tarda (PCT) is a vesiculobullous skin disorder characterized by a defect in heme biosynthesis. Reduced activity of the hepatic enzyme uroporphyrinogen decarboxylase (URO-D) results in accumulation of photosensitive porphyrins; this ultimately leads to the skin fragility and blistering that is characteristic of this disease. The majority of cases of PCT are associated with acquired deficiencies of the enzyme URO-D, secondary to hepatic injury precipitated by medications or infections. Less commonly, PCT has been documented in patients with end-stage renal disease. The pathogenesis of PCT in long-term hemodialysis (HD) has been attributed to many factors, but the following mechanisms have been implicated: (i) decreased hepatic URO-D activity due to suppressive effects of iron and other hepatotoxins and (ii) poor porphyrin clearance by renal replacement therapies. We report a case of PCT that developed in a patient on maintenance HD for 4 years. He had a history of hepatitis C and evidence of iron overload. However, as the patient was anemic, therapeutic phlebotomy was problematic and therefore erythrocyte-stimulating agents were maximized to mobilize iron stores and allow phlebotomy. With this treatment, the patient's skin lesions improved in conjunction with decreasing ferritin levels.
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PMID:Bullous skin lesions in a patient undergoing chronic hemodialysis. 2033 20

Tuberculosis is caused by Mycobacterium tuberculosis, one of the most successful and deadliest human pathogen. Aminoglycosides resistance leads to emergence of extremely drug resistant strains of M. tuberculosis. Iron is crucial for the biological functions of the cells. Iron assimilation, storage and their utilization is not only involved in pathogenesis but also in emergence of drug resistance strains. We previously reported that iron storing proteins (bacterioferritin and ferritin) were found to be overexpressed in aminoglycosides resistant isolates. In this study we performed the STRING analysis of bacterioferritin & ferritin proteins and predicted their interactive partners [ferrochelatase (hemH), Rv1877 (hypothetical protein/probable conserved integral membrane protein), uroporphyrinogen decarboxylase (hemE) trigger factor (tig), transcriptional regulatory protein (MT3948), hypothetical protein (MT1928), glnA3 (glutamine synthetase), molecular chaperone GroEL (groEL1 & hsp65), and hypothetical protein (MT3947)]. We suggested that interactive partners of bacterioferritin and ferritin are directly or indirectly involved in M. tuberculosis growth, homeostasis, iron assimilation, virulence, resistance, and stresses.
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PMID:Role of Bacterioferritin & Ferritin in M. tuberculosis Pathogenesis and Drug Resistance: A Future Perspective by Interactomic Approach. 2864 44


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