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Query: UMLS:C0240066 (iron deficiency)
 7,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ten patients with manifest iron deficiency and without documented relationship to phenylketonuria patients were orally loaded with 25 mg/kg of L-(2H5)phenylalanine. Before loading, the fasting phenylalanine-tyrosine plasma ratio was determined and after loading, the concentrations of labeled and nonlabeled phenylalanine and tyrosine were determined in five consecutive plasma samples. With respect to the fasting phenylalanine-tyrosine ratio and to the post-load ratios of labeled phenylalanine over labeled tyrosine, the iron-deficient patients showed data intermediate between those of normals and heterozygotes for phenylketonuria. Compared to a 100% in vivo activity of phenylalanine hydroxylase in normals and a circa 37% activity in heterozygotes for classic phenylketonuria, iron-deficient patients with an average hemoglobin of 8.6 +/- 1 g/dl showed an activity of circa 56%. After normalization of their iron status, four patients were subjected again to the L-(2H5)phenylalanine-loading test. For three of these individuals, test results shifted into the range of normal.
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PMID:Impaired phenylalanine-tyrosine conversion in patients with iron-deficiency anemia studied by a L-(2H5)phenylalanine-loading test. 376 33

The effects of dietary-induced iron deficiency on fetal and maternal metabolism were studied in the rat. Concentrations of phenylalanine, but not tyrosine, were significantly elevated in plasma from iron-deficient maternal and fetal rats at day 20 of gestation with individual fetal plasma levels of phenylalanine as high as 10 mg per 100 ml. Concentrations of total 5-hydroxyindole compounds were significantly decreased in brain tissue from iron-deficient fetuses (day 20 of gestation), suggesting that synthesis of the compounds may be inhibited by iron deficiency. Mitochondrial NADH oxidase activity was markedly decreased (60%) in homogenates of fetuses at day 14 of gestation and may account for the high fetal resorption rate and small fetal size observed in the rat in iron deficiency.
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PMID:Iron deficiency in the rat: biochemical studies of fetal metabolism. 663 89

Homochiral-cis-cyclohexa-3,5-diene-1,2-diols are important synthons. We found a way to produce trans-configured homochiral diols using recombinant Klebsiella pneumoniae 62-1. Transformation of this mutant (Phe- Trp- Tyr-) with plasmids carrying genes involved in chorismic and isochorismic acid metabolism leads to the production of either (+)-trans-(2S,3S)-2,3-dihydroxycyclohexa-4,6-dienecarboxylic acid or (-)-trans-(3R,4R)-3,4-dihydroxycyclohexa-1,5-dienecarboxylic acid, with a yield of 70 or 90 mg (1 culture broth)-1, respectively. The metabolic shift from one diene to the other is caused by a change in activity of isochorismate hydroxymutase and/or isochorismatase which in turn results from growth under iron deficiency or overexpression of genes (entC and/or entB) involved in chrismate metabolism.
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PMID:Bacterial production of transdihydroxycyclohexadiene carboxylates by metabolic pathway engineering. 893 26

The enzyme ferric reductase catalyses the reduction of Fe(III) as a prerequisite to its transportation across the cell membrane. Duodenal mucosal biopsies from iron overloaded patients with genetic haemochromatosis (GH) have increased ferric reductase activity and iron absorption compared with controls, yet the GH mucosa is iron deficient. A similar GH-related iron deficiency is also seen in macrophages. The aim of this study was to investigate whether macrophage ferric reductase activity is altered in GH, and to determine ferric reductase activity in monocytes and differentiated macrophages. The erythroleukaemic K562 cell line was studied as a clonal reference cell line. The basal K562 ferric reductase activity is characteristic of a membrane bound enzyme, being both temperature and protease sensitive. Ferric reductase activity was also demonstrated in human leucocyte, monocyte and macrophage preparations. Assays of K562 and macrophage cell supernatants confirmed that the ferric reductase activity was not due to a secreted factor. Assay of ferric reductase in normalized-iron and iron-enriched (100 microM ferric citrate) conditions showed no significant difference between Cys282Tyr (Cys282-->Tyr) homozygous GH macrophages and Cys282-Tyr negative control activities (P>0.05). However, a 900% increase in ferric reductase activity was observed during monocyte to macrophage differentiation (P<0.05), possibly reflecting the co-ordinate up-regulation of iron metabolism in these cells. The demonstration of approx. 25% activity after macrophage differentiation at high free-iron concentrations compared with 'normalized' iron is consistent with repression of human ferric reductase activity by iron. The identification of the human ferric reductase gene and its protein will ultimately provide insight into its regulation and role in mammalian iron metabolism.
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PMID:Monocyte-macrophage ferric reductase activity is inhibited by iron and stimulated by cellular differentiation. 984 63

We describe a case of homozygosity due to the substitution of aspartic acid with histidine at position 63 of the protein encoded by the gene (known as HFE) associated with hereditary hemochromatosis. Liver biopsy did not disclose stainable iron accumulation; serum ferritin was elevated (639 ng/mL), while the transferrin saturation index was within the normal range (38.1%). As the patient was affected by chronic hepatitis C virus, the high serum ferritin could be attributed to this disease, a frequent occurrence. We also describe a case of heterozygosity for both the substitution of tyrosine with cysteine at position 282 and the substitution of histidine to aspartic acid at position 63 (so-called "compound heterozygosity"). The patient had the typical biochemical abnormalities of iron overload: transferrin saturation index of 53.1% and elevated serum ferritin (658 ng/mL). The removal of > 5 g of iron by phlebotomies did not precipitate iron deficiency. Although the patient refused to undergo liver biopsy, clinical evidence alone enabled a diagnosis of hemochromatosis. These two cases concord with the present scientific orientation, i.e.: 1) homozygosity for the major mutation is associated with the phenotypical (clinical) picture of hemochromatosis, but compound heterozygosity also determines significant iron metabolism abnormalities; 2) homozygosity for the minor mutation does not appear to determine important phenotypical abnormalities.
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PMID:[Significance of "minor" genetic mutations in hereditary hemochromatosis: 2 case reports]. 1105 64

Thy-1, a glycosyl-phosphatidylinositol (GPI)-linked integral membrane protein, may play a role in stabilizing synapses. Thy1 was identified in a gene expression analysis as iron responsive, and subsequent cell culture and animal models of iron deficiency expanded this finding to the protein. The importance of Thy1 in influencing neurotransmitter feedback mechanisms led to this study to determine the relative effects of Thy1 deficiency and dietary iron deficiency on the dopaminergic system in the mouse striatum. The model for this analysis was the Thy1 null mutant mouse in the presence or absence of dietary iron deficiency. The results revealed significant differences in dopaminergic profiles associated with Thy1 and iron deficiency and also a sex effect. For example, both iron deficiency and the absence of Thy1 are associated with increased dopamine in both sexes, but the dopamine transporter is increased in these experimental groups only in female mice. In male mice, the increase in dopamine transporter is found only in the Thy1 null mutants. Increases in vesicular monoamine transporter and phosphorylated tyrosine hydroxlyase are found only in iron-deficient mice. In contrast decreased release of dopamine from synaptosomes is found only in the Thy1 null mutant animals. In general, these results indicate that a loss of Thy1 can influence the dopaminergic profile in the striatum. Furthermore, the results reveal consistent differences in the dopaminergic profile in Thy1 knockout mice compared with iron-deficient mice, indicating that the effects of iron deficiency are not due only to a change in Thy1 expression.
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PMID:Comparative study of the influence of Thy1 deficiency and dietary iron deficiency on dopaminergic profiles in the mouse striatum. 1861 41

Fetal-neonatal iron deficiency alters hippocampal neuronal morphology, reduces its volume, and is associated with acute and long-term learning impairments. However, neither the effects of early-life iron deficiency anemia on growth, differentiation, and survival of hippocampal neurons nor regulation of the neurotrophic factors that mediate these processes has been investigated. We compared hippocampal expression of neurotrophic factors in male rats made iron deficient (ID) from gestational d 2 to postnatal d (P) 7 to iron-sufficient controls at P7, 15, and 30 with quantitative RT-PCR, Western analysis, and immunohistology. Iron deficiency downregulated brain-derived neurotrophic factor (BDNF) expression in the hippocampus without compensatory upregulation of its specific receptor, tyrosine-receptor kinase B. Consistent with low overall BDNF activity, we found lower expression of early-growth response gene-1 and -2, transcriptional targets of BDNF signaling. Doublecortin expression, a marker of differentiating neurons, was reduced during peak iron deficiency, suggesting impaired neuronal differentiation in the ID hippocampus. In contrast, iron deficiency upregulated hippocampal nerve growth factor, epidermal growth factor, and glial-derived neurotrophic factor accompanied by an increase in neurotrophic receptor p75 expression. Our findings suggest that fetal-neonatal iron deficiency lowers BDNF function and impairs neuronal differentiation in the hippocampus.
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PMID:Early-life iron deficiency anemia alters neurotrophic factor expression and hippocampal neuron differentiation in male rats. 1902 78

Although the neurophysiological correlates of sleep have been thoroughly described, genetic mechanisms that control sleep architecture, long surmised from ethological studies, family histories and clinical observations, have only been investigated during the past decade. Key contributions to the molecular understanding of sleep have come from studies in Drosophila, benefitting from a strong history of circadian rhythm research. For instance, a number of recent papers have highlighted the role of the E3 ubiquitin ligase Cullin-3 in the regulation of circadian rhythm and sleep. We propose that different Cullin-3 substrate adaptors may affect specific molecular pathways and diverse aspects of circadian rhythm and sleep. We have previously shown that mutations in BTBD9, a risk factor for Restless Legs Syndrome (RLS) encoding a Cullin-3 substrate adaptor, lead to reduced dopamine, increased locomotion and sleep fragmentation. Here, we propose that Cullin-3 acts together with BTBD9 to limit the accumulation of iron regulatory proteins in conditions of iron deficiency. Our model is consistent with clinical observations implicating iron homeostasis in the pathophysiology of RLS and predicts that lack of BTBD9 leads to misregulation of cellular iron storage, inactivating the critical biosynthetic enzyme Tyrosine Hydroxylase in dopaminergic neurons, with consequent phenotypic effects on sleep.
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PMID:An emerging role for Cullin-3 mediated ubiquitination in sleep and circadian rhythm: insights from Drosophila. 2345 37

We report the case of a 73-year-old man with massive swelling of the lower extremities, with a chronic and rather uncommon form of stasis dermatitis - stasis papillomatosis. The patient was also diagnosed with severe heart failure, including dilated cardiomyopathy, hypothyroidism that required a substantial dose of exogenous tyrosine, microcytic and megaloblastic anemia, iron deficiency, and type 2 diabetes. The cause of stasis dermatitis lesions is not completely understood. It may be caused by the allergic reaction to some epidermal protein antigen formation or chronic damage to the dermal-epidermal barrier that makes the skin more sensitive to irritants or trauma. It has, however, been suggested that the term stasis dermatitis should be used to refer only to cases caused by chronic venous insufficiency, which belongs to a group of lifestyle diseases and affects both women and men more and more frequently.
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PMID:Stasis papillomatosis with cardiac complications and vein insufficiency. 2622 26

In this study, we investigated whether alterations in plasticity markers such as brain-derived neurotrophic factor (BDNF), p75 neurotrophin receptor (p75NTR) and tyrosine receptor kinase B (TrkB) are underlying iron deficiency (ID)-induced cognitive impairments in iron depleted piglets. Newborn piglets were either fed an iron-depleted diet (21mg Fe/kg) or an iron-sufficient diet (88mg Fe/kg) for four weeks. Subsequently, eight weeks after iron repletion (190-240mg Fe/kg) we found a significant decrease in mature BDNF (14kDa) and proBDNF (18kDa and 24kDa) protein levels in the ventral hippocampus, whereas we found increases in the dorsal hippocampus. The phosphorylation of cAMP response element binding protein (CREB) follows the mature BDNF protein level pattern. No effects were found on BDNF and CREB protein levels in the prefrontal cortex. The protein levels of the high affinity BDNF receptor, TrkB, was significantly decreased in both dorsal and ventral hippocampus of ID piglets, whereas it was increased in the prefrontal cortex. Together, our data suggest a disrupted hippocampal plasticity upon postnatal ID.
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PMID:Early-postnatal iron deficiency impacts plasticity in the dorsal and ventral hippocampus in piglets. 2833 Aug 28


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