Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
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Treatment of growing cultures of Mycobacterium smegmatis with alkylating agents (methyl methanesulphonate, ethyl methanesulphonate, nitrogen mustard, or mitomycin C) or with ultraviolet light resulted in enhanced specific activities of a DNA polymerase and of an ATP-dependent deoxyribonuclease. Similar results had previously been obtained with hydroxyurea and with iron limitation. The three of these treatments which were tested (methyl methanesulphonate, mitomycin C and hydroxyurea) produced strand breaks or alkali-labile regions in the DNA of this organism. The increased enzyme activities could be prevented by simultaneous treatment with inhibitors of protein synthesis. In contrast, treatment of the cultures with intercalating agents (ethidium bromide, acridine orange, or proflavine), 5-fluorouracil, caffeine, or nalidixic acid, inhibited DNA synthesis without increasing the enzyme activities. These treatments did not produce strand breaks in the DNA of this organism. The results support the hypothesis that, in M. smegmatis, damage to DNA induces increased synthesis of enzymes associated with DNA repair.
Mol Gen Genet 1977 Feb 15
PMID:Increased DNA polymerase and ATP-dependent deoxyribonuclease activities following DNA damages in mycobacterium smegmatis. 84 85

1. We have studied activity of delta-aminolaevulinate synthase in needle liver biopsy specimens obtained from 12 human cirrhotic subjects, five subjects who had ingested anticonvulsants and from control subjects. Liver iron concentrations and quantitative urinary excretions of porphyrins plus their precursors were also determined. 2. In liver homogenates from subjects of each group, addition of an exogenous system for generation of succinyl-coenzyme A (CoA), including succinic thiokinase, resulted in appreciable enhancement of activity beyond that obtained without this system. 3. Mean activities for delta-aminolaevulinate synthease were not significantly different among patient groups when assayed without the exogenous succinyl-CoA-generating system, but liver homogenates from cirrhotic patients and subjects ingesting anticonvulsants had significantly higher activities than control subjects in the presence of the succinyl-CoA-generating system. 4. Although mean liver iron concentration in the cirrhotic group was slightly higher than in control subjects, and in control subjects there was some correlation between liver iron concentration and activity of delta-aminolaevulinate synthase, variations in this activity could not be accounted for solely on the basis of chronic hepatic deposition. Nor were these variations ascribable to differences among subjects in ingestion of ethanol before biopsy or severity of hepatic inflammation as judged biochemically and histologically. 5. Cirrhotic subjects excreted more uro- and copro-porphyrin than control subjects, whereas subjects ingesting anticonvulsants excreted more delta-aminolaevulinic acid and porphobilinogen than control subjects. However, these increases were small and not sufficient to account for all the increased delta-aminolaevulinic acid which potentially could have been formed by these subjects. 6. These considerations raise the possibilities that in vivo: (a) rate of human hepatic synthesis of delta-aminolaevulinic acid is modulated by the supply of succinyl-CoA; (b) the rate of hepatic synthesis of haem is increased in cirrhotic patients and subjects ingesting anticonvulsants; (c) other important routes exist for disposition of haem precursors in these subjects, besides utilization for haem synthesis.
Clin Sci Mol Med 1977 May
PMID:Human hepatic delta-aminolaevulinate synthase: requirement of an exogenous system for succinyl-coenzyme A generation to demonstrate increased activity in cirrhotic and anticonvulsant-treated subjects. 86 44

The sequences of two rubredoxins isolated from the sulfate reducing bacteria: Desulfovibrio vulgaris and Desulfovibrio gigas have been elucidated. They have similar sequences but many more differences occur than would be expected from two bacteria of the same genus. Of the 52 sites, only 37 are occupied by identical residues. The primary structures are compared with those of the anaerobic bacteria rubredoxins of Clostridium pasteurianum, Micrococcus aerogenes, Pseudomonas oleovorans and Peptostreptococcus elsdenii: only 12 identities are found, mostly in the two clusters that contain two iron-bound cysteines each. A phylogenetic tree based on the primary structures is presented and possible relations with plant and bacterial ferredoxins are discussed. A secondary and tertiary structure stereochemically compatible with the sequence data, is proposed.
J Mol Evol 1977 Apr 29
PMID:Phylogenetic studies of two rubredoxins from sulfate reducing bacteria. 86 18

1. A new method for the measurement of uroporphyrinogen decarboxylase (EC 4. 1.1.37) in rat liver homogenates, with 5- carboxyl porphyrinogen as substrate, is described. 2. The administration of a diet containing 0-3% (w/w) hexachlorobenzene produces porphyria in female Wistar rats after a delay of at least 4 weeks. The development of porphyria is accompanied by a progressive fall in hepatic uroporphyrinogen decarboxylase activity to 18% of control values after 11 weeks. The features of hexachlorobenzene prophyria are consequences of this enzyme defect. 3. Feeding with hexachlorobenzene did not lead to the accumulation of iron in the liver. It is suggested that hexachlorobenzene or a metabolite acts directly to decrease the activity of the enzyme.
Clin Sci Mol Med 1976 Jul
PMID:The effect of the porphyrogenic compound, hexachlorobenzene, on the activity of hepatic uroporphyrinogen decarboxylase in the rat. 93 68

Iron uptake and micelle formation in ferritin and apoferritin have been followed both spectrophotometrically and by means of sedimentation velocity experiments. Information was thus obtained on the molecular weight distribution of the reconstitution product. To achieve incorporation 'native' ferritin (whole ferritin as purified from horse spleen), 'native' apoferritin (apoferritin prepared by fractionation of ferritin preparations) and 'reduced' apoferritin (apoferritin prepared by reduction of ferritin by dithionite or ascorbic acid) have been incubated with ferrous salts in the presence of oxidizing agents under different experimental conditions. Although some iron is incorporated in 'native' ferritin, full saturation is not achieved and the molecular weight distribution of the incubated products remains heterogeneous. 'Native' and 'reduced' apoferritin show a similar iron incorporation, but the reconstitution products markedly differ in terms of their iron distribution. Ferritin reconstituted from 'native' apoferritin has a broad molecular weight distribution, while that reconstituted from 'reduced' apoferritin is characterized by a narrow, homogeneous molecular weight distribution. However treatment of apoferrition with reducing or oxidizing agents prior to the incubation alters the characteristics of the iron distribution without changing the iron incorporation properties. These results point to a role of the protein moiety not only in iron oxidation, but also in micelle formation.
Mol Cell Biochem 1976 Oct 30
PMID:Studies on iron uptake and micelle formation in ferritin and apoferritin. 100 97

To clarify the influence of protein surrounding on the heme reactivity in heme proteins the effect of interaction between a porphyrin ring and pi-acceptor molecule, 1,2,4-trimethyl-pyridinium (TMP), on the affinity of deuteroheme to axial ligands (imidazole and cyanide) has been studied as a model system. It is shown that TMP induces the fourfold decrease in equilibrium constant of imidazole to deuteroheme. From the analysis of the two stages for cyanide binding it is concluded that TMP decreases the binding constant of the first cyanide by 40 times and does not apparently influence the second ligand binding. The effect of TMP on the reactivity of deuteroheme to axial ligands is interpreted as a result of a decrease in the electron density on the iron orbitals which is due to the altered pi-eleectron density in the porphyrin pi-system through the donor-acceptor interaction with TMP molecules. The possible significance of the contacts between the porphyrin and neighboring amino acid residues in determining heme affinity to axial ligands is discussed.
Mol Biol (Mosk)
PMID:[Effect of porphyrin ring ligands on the affinity of heme iron to axial ligands]. 105 78

1. Marrow-iron stores were absent or reduced in twenty-three of thirty-nine patients studied within 52 months of starting maintenance haemodialysis. 2. Oral iron was given to twelve patients (group I) with absent or reduced, and to eleven patients (group II) with normal or increased marrow-iron stores. 3. A significant increase in mean haemoglobin concentration and marrow iron was observed in group I. No significant change in mean haemoglobin concentration or marrow iron occurred in group II. Mean haemoglogin concentration after treatment was significantly higher in group I than in group II. 4. The four patients who had normal or increased marrow iron and who received no oral iron all suffered a fall in haemoglobin concentration, and three of them showed a reduction in marrow iron. 5. These findings indicate that continuous oral iron therapy should be given to all patients on maintenance dialysis to correct or prevent iron deficiency.
Clin Sci Mol Med Suppl 1975 Jun
PMID:Iron therapy in maintenance haemodialysis. 105 83

1. Haematological investigation and blood volume measurements were carried out on forty male middle and long distance runners and twelve non-athletes. 2. The distribution of haemoglobin concentration, packed cell volume, erythrocyte count, total ironbinding capacity, serum and erythrocyte folate and serum vitamin B12 concentrations were essentially the same in atheletes and non-athletes. The mean serum iron concentration was higher in non-athletes than in athletes. There was no difference in the above measurements between athletes taking iron and/or folate and athletes not taking these supplements. 3. Blood volume and total body haemoglogin were on average 20% higher in the atheletes than in the non-athletes. 4. There was no correlation between haemoglobin concentration and blood volume in athletes. The evidence of this study suggests that haemoglobin concentration and blood volume are independently controlled. 5. 2,3-Diphosphoglycerate concentration in the erythrocytes was higher in the athletes than in the non-athletes; the mean values were 15-9 and 14-2 mumol/g of haemoglobin respectively.
Clin Sci Mol Med 1975 Feb
PMID:Haematological status of middle- and long-distance runners. 111 32

1. The activity of monoamine oxidase, when assayed with four substrates, was significantly lowered in platelets prepared from the blood of patients with iron-deficiency anaemia. 2. Treatment with oral iron preparations restored platelet monoamine oxidase activity to normal in those patients whose serum iron concentrations also returned to normal. 3. Platelet monoamine oxidase activity remained low if treatment failed to restore serum iron concentration to within normal limits.
Clin Sci Mol Med 1975 Apr
PMID:Human platelet monoamine oxidase activity in iron-deficiency anaemia. 112 21

1. Transferrin was isolated from umbilical cord blood by means of gel filtration on Sephadex G-150 and ion exchange chromatography on DEAE-Sephadex A-50, and its properties were compared with those of transferrin isolated from human adult blood. 2. Both glycoproteins were able to bind a maximum of two atoms of iron per molecule and have very similar amino acid and carbohydrate compositions. 3. The molecular weight of cord-blood transferrin, assessed by equilibrium centrifugation, was 78200, and its sedimentation velocity appeared to be 5-2S. 4. Cord-blood transferrin and adult blood transferrin were found to be immunochemically identical. 5. No differences could be detected between the transferrins in their capacities to deliver iron to immature erythrocytes derived from rat bone marrow, which indicates that the rapid transport of iron across the placenta cannot be explained by differences between foetal and maternal transferrin.
Clin Sci Mol Med 1975 May
PMID:Isolation, characterization and function of cord-blood transferrin. 112 26


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