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At least 199 records · Page 11Linked to original sources
PubMed2006

The Rhizobium leguminosarum regulator IrrA affects the transcription of a wide range of genes in response to Fe availability.

We show that an unusual transcriptional regulator, called IrrA, regulates many genes in the symbiotic N2-fixing bacterium Rhizobium leguminosarum in response to iron availability. Several operons in R. leguminosarum are expressed at lower levels in cells grown in Fe-depleted compared to Fe-replete medium. These include hemA1, which encodes the haem biosynthesis enzyme amino-levulinic acid synthase; sufS2BCDS1XA, which specify enzymes for FeS cluster synthesis; rirA, a global, Fe-responsive transcriptional repressor; RL0400, which likely encodes an unusual FeS cluster scaffold; and the possible ferri-siderophore ABC transporter rrp1. Reduced expression in Fe-depleted medium was effected by IrrA, a member of the Fur super-family, which in Bradyrhizobium, the symbiont of soybeans, and in the mammalian pathogen Brucella, is unstable in Fe-replete conditions, due to an interaction with haem. The R. leguminosarum IrrA likely interacts with ICE (iron-control element) motifs, conserved sequences near the promoters of its target genes. The rirA, sufS2BCDS1XA and rrp1 genes are also known to be regulated by RirA, which represses their expression in Fe-replete medium. We present a possible model for iron-responsive gene regulation in Rhizobium, in which the IrrA and RirA regulators, working in parallel, respond to the intracellular availability of haem and, possibly, of FeS clusters respectively. Thus, these regulators may sense the physiological consequences of extraneous Fe concentrations, rather than the concentration of Fe per se, as happens in those bacteria (e.g. Escherichia coli) in which the ferric uptake regulator Fur is the global Fe-responsive gene regulator.

Bacterial Proteins↗
PubMed1994

Preferential heme transport through endoplasmic reticulum associated with mitochondria in rat liver.

The transport of de novo synthesized protoheme into the conventional microsomal fraction and endoplasmic reticulum associated with mitochondria (MAER) was studied by injecting amino[14C]levulinic acid (ALA) into phenobarbital-treated rats to evaluate the role of MAER in the trafficking of heme between mitochondria and endoplasmic reticulum. In mitochondria, the specific radioactivity of the radiolabeled heme reached a maximum level at 4 min after the injection of 14C-ALA. The specific radioactivity in cytosol was about 2-fold lower than that in microsomes, suggesting that the cytosolic pathway of the heme transport from mitochondria to endoplasmic reticulum is not predominant, because the specific radioactivity of heme in cytosol should be higher than that in microsomes if heme is transported mainly through cytosol. MAER showed higher specific radioactivity than the conventional microsomal fraction up to 4 min and thereafter the specific radioactivities in MAER and the conventional microsomal fraction became nearly the same. The extents of decrease in cytochrome P-450 and the radioactivity in microsomes by the treatment with allylisopropylacetamide which destroyed cytochrome P-450 but not cytochrome b5, were essentially the same, suggesting that most of the radiolabeled heme in microsomes was incorporated into cytochrome P-450. These results suggest that MAER is a preferential site for the protoheme transport from mitochondria to endoplasmic reticulum.

Animals↗
PubMed1977

Mitochondrial biogenesis in cultured mammalian cells. II. Mitochondrial protein and phospholipid synthesis in chloramphenicol-treated BHK-21 cells.

The effect of growth of BHK-21 cells in chloramphenicol on the synthesis of cellular proteins and phospholipids has been examined. The incorporation of leucine into total cellular proteins, or into the proteins of specific subcellular fractions are not significantly reduced by cell culture in the presence of chloramphenicol. In cells treated with cycloheximide, a small amount of chloramphenicol-sensitive labelling of protein was detected within the first hour of exposure to the drug. Chloramphenicol inhibits the incorporation of delta-amino-levulinic acid into hemoproteins, only if it is present during both the 48-h culturing and 4-h labelling period. De novo synthesis of cellular lipids as measured by pulse labelling with 32Pi or [3H]glycerol, is decreased in chloramphenicol-treated cells. This decrease is observed in all sub-cellular fractions, although the mitochondrial fraction is most affected. All phospholipids are affected, with diphosphatidylglycerol labelling reduced to the greatest extent. Although fatty acid synthesis is inhibited, the labelling of diphosphatidylglycerol with fatty acids is stimulated on chloramphenicol treatment.

Acetates↗
PubMed1981

Urinary excretion of succinylacetone and delta-aminolevulinic acid in patients with hereditary tyrosinemia.

Succinylacetone was excreted in the urine from four patients, with hereditary tyrosinemia i.e., two patients with the severe infantile type with fatal outcome and two patients with less severe juvenile form. In the urine from two patients with neonatal transient tyrosinemia and from normal individuals succinylacetone was not detectable. The urinary excretion of delta-aminolevulinic acid was also increased in all patients with hereditary tyrosinemia compared to patients with neonatal transient tyrosinemia and to normal individuals. The results presented support the hypothesis of a deficiency of fumarylacetoacetase in hereditary tyrosinemia. Furthermore an analytical method for the quantitative determination of succinylacetone in urine using GC-MS is described.

Acetoacetates↗
PubMed1987

Evidence for a dipyrromethane cofactor at the catalytic site of E. coli porphobilinogen deaminase.

Porphobilinogen deaminase isolated from Escherichia coli is shown to contain a dipyrromethane cofactor (DPMC) linked covalently to the enzyme. The structure of the cofactor is proposed on the basis of its reaction with Ehrlich's reagent and from its chemical properties. The cofactor is involved in the binding of intermediates during the catalytic reaction but is not incorporated into the product preuroporphyrinogen, E. coli strains containing the cloned porphobilinogen deaminase gene (hemC) when grown on 5-amino[14C]-levulinic acid incorporate 14C radioactivity specifically into the dipyrromethane cofactor of porphobilinogen deaminase.

Ammonia-Lyases↗
PubMed1988

Identification of a cysteine residue as the binding site for the dipyrromethane cofactor at the active site of Escherichia coli porphobilinogen deaminase.

The dipyrromethane cofactor of Escherichia coli porphobilinogen deaminase was specifically labelled with 13C by growth of the bacteria in the presence of 5-amino[5-13C]levulinic acid. Using 13C-NMR spectroscopy, the structure of the cofactor was confirmed as a dipyrromethane made up of two linked pyrrole rings each derived from porphobilinogen. The chemical shift data indicate that one of the pyrrole rings of the cofactor is covalently linked to the deaminase enzyme through a cysteine residue. Evidence from protein chemistry studies suggest that cysteine-242 is the covalent binding site for the cofactor.

Aminolevulinic Acid↗
PubMed1985

Hepatic heme metabolism and cytochrome P450 in cirrhotic rat liver.

Cytochrome P450 levels are often low in the cirrhotic liver but the reason for this has not been established. Because changes in heme metabolism may reduce hepatic levels of cytochrome P450, the relationship of heme turnover to cytochrome P450 levels has been examined in rats with cirrhosis. Cirrhosis was produced by repeated carbon tetrachloride inhalation. In animals with cirrhosis, hepatic microsomal cytochrome P450 content was significantly less (32%) than in controls. Heme synthesis was assessed by measuring the activity of mitochondrial delta-amino-levulinic acid synthetase and also by determining the incorporation (within 30 min) of radiolabeled delta-aminolevulinic acid into the microsomal heme fraction. Both these parameters were normal in rats with CCl4-induced cirrhosis. In addition, the activity of microsomal heme oxygenase, the rate-limiting enzyme in catabolism of heme to bilirubin, was not altered. Cytochrome P450 heme degradation was then determined directly by injecting radiolabeled delta-aminolevulinic acid and measuring radioactivity in CO-binding particles (microsomes incubated with protease to remove cytochrome b5) prepared at various times thereafter. By this method, the degradation rate of cytochrome P450 heme did not differ between rats with cirrhosis and controls. Finally, the availability of hepatic heme for formation of hemoproteins was deemed to be satisfactory in cirrhotic liver because tryptophan pyrrolase saturation was comparable with controls, and also because heme administered in vivo did not enhance hepatic clearance of the cytochrome P450 substrate antipyrine. The failure to find defective heme biosynthesis or accelerated heme breakdown and the evidence that heme is available in amounts that do not restrict hemoprotein formation indicate that aberrant heme metabolism is not the cause of low cytochrome P450 levels in this rat model of cirrhosis.

Aminolevulinic Acid↗
PubMed1982

Purification and characterization of animal porphobilinogen synthases--II. Dog liver porphobilinogen synthase.

1. A method is described for the purification of porphobilinogen synthase (PBG-S) from dog liver (acetone dry powder; ammonium sulfate fractionation; controlled heat denaturation; ion exchange chromatography; gel filtration). The 911-fold purified enzyme with a specific activity of 372 mU/mg and 6.2 nkat/mg enzyme protein, respectively, appears as a single band in disc electrophoresis. 2. The optimum pH of the enzyme is 6.8; the Michaelis constant Km = 1.77 x 10(-4) M with 5-amino-levulinic acid as substrate. 3. The determination of the molecular weight of the native multisubunit enzyme (268,000 dalton) and of the subunit (33,500 dalton) are in favour of an octameric structure. 4. The acyl group blocking the N-terminus has been identified as an acetyl group (hydrazinolysis; dansylation; TLC; HPLC). 5. The amino acid composition of the PBG-S subunit is as follows CH3CO-NH-(Asx22Thr9-10Ser18Glx28-29Pro20-21Gly22Ala35-37Val23-25Met5 Ile8-9Leu32-33Tyr10Phe12Lys12Cys3His7Arg22Trp3)-Ala-Leu-COOH. 6. In the presence of ganidinium chloride only one free sulfhydryl group per subunit (3 cysteine residues) could be detected. 7. The purified enzyme contains 0.56 gram atoms of zinc per octamer (neutron activating analysis).

Amino Acids↗
PubMed1993

Collapse of K+ and ionic balance during photodynamic inactivation of leukemic cells, erythrocytes and Staphylococcus aureus.

1. The immediate and fast ionic fluxes in Friend erythroleukemic cells (FELC), erythrocytes and Staphylococcus aureus during short intervals of porphyrin mediated photosensitization were determined uniquely by X-ray microanalysis (XRMA) combined with electron microscopy. 2. Photodynamic inactivation of FELC was mediated by either endogenous protoporphyrin induced by 5-amino levulinic acid (5-ALA), or Photofrin-II. We describe the predominant phenomena of > 85% K-loss within 2-10 min of photoactivation. However the accompanied Na inflow and the collapse of the cellular balance of elemental-composition were inconsistent and acted as a function of cell damage. 3. Erythrocytes treated with hematoporphyrin (HP) lost most of their intracellular K yet instantly gained Na. Nevertheless the K/Na molar ratio of the control erythrocytes was nearly 12/1 while after photosensitization and K loss it changed to 1/1. 4. The S. aureus bacteria photosensitized with HP showed entire K-loss as well as marked Na efflux which increased with irradiation time; this was accompanied by the decline of other cell elements. 5. The prevailing K loss in FELC, erythrocytes and bacteria during the first minutes of photosensitization is deduced to be an immediate primary consequence of the photodynamic effect, while other ionic changes are joined in order with the development of cellular damage.

Adolescent↗
PubMed1988

v-erbA specifically suppresses transcription of the avian erythrocyte anion transporter (band 3) gene.

Previous work has established that the v-erbA oncogene inhibits the temperature-induced differentiation of chick erythroblasts transformed with temperature-sensitive oncogene mutants. Here we demonstrate that v-erbA in differentiating erythroblasts specifically arrests expression of the erythrocyte anion transporter (band 3) gene at the transcriptional level. The v-erbA-induced differentiation block can be overcome by inducing cells to differentiate at alkaline pH. Under these conditions, which possibly impair biological activity of v-erbA, the maturing cells now express the anion transporter gene at high levels. However, its transcription is specifically and rapidly suppressed if v-erbA activity is restored by culturing the cells at neutral pH. Similar but less pronounced inhibition of gene expression by v-erbA was observed for the delta-amino-levulinic acid synthase gene. Additional evidence obtained with an inhibitor of band 3 activity suggests that the v-erbA-induced inhibition of band 3 gene expression is at least partly responsible for the differentiation block caused by this oncogene.

5-Aminolevulinate Synthetase↗
PubMed1975

Psychophysiologic effects of early lead exposure.

In several separate experiments neonatal rats were intubated daily with 9, 27 or 81 mg lead acetate/kg of body weight throughout their 3-week postnatal period of development. Based on average body weights, the total daily lead intake was 0.156, 0.454 or 1.384 mg lead per animal, respectively (in addition to normal lead intake from the environment). Subtle and specific behavioral changes, involving an inability to attenuate inappropriate behavior in a two-way shuttle or a habit-reversal operant task, occurred in offspring following exposure to a minimum of 0.454 mg lead per day. The specificity of this central dysfunction was such that motor activity was normal, stress responsiveness remained unaffected and simple learning ability was comparable to that of controls. The only indication of a central neurochemical modification accompanying this behavioral defect was a tendency for telencephalic acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities to be depressed, suggesting a possible involvement of the cholinergic system. Steady-state levels of brain monoamines were unaltered. The experimental weanlings displayed an inhibition of blood delta-amino levulinic acid dehydratase (ALAD) activity, a parallel reduction in regional brain ALAD activity, a moderate reduction in hematocrit and hemoglobin and an increase in kidney weight. This latter effect occurred even at the lowest level of lead intake, 0.156 mg lead per day.

Age Factors↗