Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.1.4 (deaminase)
 5,113 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Erythropoietin (Epo) was found to act as a concentration-dependent inducer of aminolevulinic acid (ALA) synthase and porphobilinogen (PBG) deaminase in normal human bone marrow in culture. Epo increased enzymatic activities in individual plated nucleated cells. At a low concentration of Epo, heme oxygenase activity did not change in human bone marrow erythroid progenitor cells. However, Epo at a concentration of 2 U/ml increased heme oxygenase as demonstrated by an increase in both the enzyme protein and its mRNA. In experiments with an inhibitor of heme synthesis, succinylacetone (SA), Epo failed to stimulate erythroid colony-forming unit (CFU-E) growth, but this CFU-E inhibition by SA was completely overcome by the addition of hemin. Epo nevertheless potentiated induction of ALA synthase in the presence of SA. Hemin exerted its regulatory role by negative feedback on ALA synthase in the presence of SA and Epo. Heme potentiated Epo action and resulted in the increase of human marrow erythroid progenitor cell proliferation and differentiation and a concomitant stimulation of ALA synthase and PBG deaminase. The potentiating effects of hemin on CFU-E growth were observed in human bone marrow cells cultured in media supplemented with fetal calf serum or serum-free media with interleukin 3 (IL-3). These results indicate that Epo is a potent inducer of ALA synthase and PBG deaminase in normal human bone marrow. In addition, our results may explain the mechanisms by which heme potentiates Epo or IL-3 enhancement of erythropoiesis. 1) Heme may stimulate the translation of several globin and nonglobin mRNAs, including those of ALA synthase and PBG deaminase; 2) as endogenous cellular heme synthesis reaches optimal levels, heme exerts its regulatory role on ALA synthase by negative feedback inhibition. Additionally, an increase in cellular heme may lead to an increase in its own degradation by induction of heme oxygenase.
Exp Hematol 1989 Sep
PMID:Erythropoietin controls heme metabolic enzymes in normal human bone marrow culture. 276 84

By the use of spin trapping agents phenyl-t-butyl nitrone (PBN) and 4-pyridyl-1-oxide-t-butyl nitrone (4-POBN) free radical species were detected in isolated hepatocytes incubated with either isoniazid, iproniazid and their respective metabolites acetyl-hydrazine and isopropyl-hydrazine. The addition of bis-nitrophenyl phosphate, an inhibitor of the acylamidase enzymes, to isolated hepatocytes decreased the free radical activation of isoniazid and iproniazid, but not that of acetyl- and isopropyl-hydrazine, confirming that the radical species were originating from the biotransformation of these latter compounds. The ESR spectra were ascribed to the trapping of, respectively, acetyl and isopropyl free radicals on the basis of the analogies of the spectral feature with those of chemically-prepared spin adducts. Comparable ESR spectra were also observed during the metabolism of acetyl- and isopropyl-hydrazines by liver microsomes and their formation was inhibited by the omission of NADP+, anaerobic incubation and enzyme denaturation. In the microsomal preparations inhibitors of the mixed function oxidase system decreased to various extents the free radical formation and a similar effect was also observed following the destruction of cytochrome P-450 induced by pretreating the rats with CoCl2. The addition of reduced glutathione also decreased the radical trapping indicating that GSH can effectively compete with the spin traps for the reaction with the free radicals. The incubation of isolated hepatocytes with isoniazid or acetyl-hydrazine reduced by 20-25% the intracellular GSH content, while a 50% decrease in GSH was present in the cells exposed to iproniazid and isopropyl-hydrazine. In the same hepatocyte preparations stimulation of lipid peroxidation and leakage of LDH were also observed during cell incubation with iproniazid and isopropyl-hydrazine, but not with isoniazid or acetyl-hydrazine and the extent of both phenomena correlated with the susceptibility of the above compounds to the free radical activation.
Biochem Pharmacol 1987 Sep 15
PMID:Spin trapping of free radical intermediates produced during the metabolism of isoniazid and iproniazid in isolated hepatocytes. 282 Apr 25

By means of agonist and enzyme experiments, the relative importance of endogenous adenosine, adenine nucleotides or other purines as modulators of cholinergic neuroeffector transmission in preparations of guinea-pig ileum muscle has been examined. Adenosine, 2-chloroadenosine, AMP, ADP, ATP and AMPPNP reversibly inhibited contractile responses to transmural stimulation of the guinea-pig ileum longitudinal muscle. 5'-adenylate deaminase dose-dependently antagonized the inhibitory effect of adenosine, AMP, ADP, ATP and AMPPNP, but not that of 2-chloroadenosine. 8-p-sulphophenyltheophylline, adenosine deaminase and 5'-adenylate deaminase enhanced contractile responses to transmural nerve stimulation. Adenosine deaminase and 5'-adenylate deaminase were virtually equiactive whereas 8-p-sulphophenyltheophylline was much more effective, and the theophylline derivative also enhanced contractile responses in preparations pretreated with adenosine deaminase or 5'-adenylate deaminase. Moreover, 8-p-sulphophenyltheophylline abolished the inhibition by dipyridamole, whereas adenosine deaminase and 5'-adenylate deaminase only partly antagonized the inhibitory effect of dipyridamole. Application of 5'-adenylate deaminase did not enhance the nerve-induced contractions in preparations pretreated with adenosine deaminase or a combination of dipyridamole and adenosine deaminase. In conclusion, adenosine deaminase and 5'-adenylate deaminase enhanced the nerve-induced contractions in the ileum, and, since 5'-adenylate deaminase was inactive after pretreatment with adenosine deaminase, this suggests that endogenous adenosine rather than 5'-adenine nucleotides modulated cholinergic neurotransmission in the ileum.(ABSTRACT TRUNCATED AT 250 WORDS)
Acta Physiol Scand 1987 Sep
PMID:On the nature of endogenous purines modulating cholinergic neurotransmission in the guinea-pig ileum. 282 30

The arrangement of the histidine utilization (hut) genes in Pseudomonas putida was established by examining the structure of a DNA segment that had been cloned into Escherichia coli via a cosmid vector. Southern blot analysis revealed that the restriction patterns of the hut genes cloned into E. coli and present in the P. putida genome were identical, indicating that no detectable DNA rearrangement took place during the cloning. Expression of the hut genes from a series of overlapping clones indicated the gene order to be hutG-hutI-hutH-hutU-hutC-hutF. The transcription directions of the different hut genes were determined by cloning the genes under control of the lambda pL promoter. This showed that hutF, encoding formiminoglutamate hydrolase, was transcribed in a direction opposite to that of the other genes. Inactivation of the cloned hut genes by Tn1000 insertion revealed that the hut genes were divided into three major transcriptional units (hutF, hutC [the repressor gene], and hut UHIG), but hutG may also be independently transcribed. When cloned individually with hutC on the same vector, hutF and hutU (which encodes urocanase) expression was induced by urocanate, indicating that these two genes each possess an operator-promoter element. Tn1000 insertions (in the cloned genes) or Tn5 insertions (in the P. putida genome) affecting the hutI or hutH gene only partially eliminated hutG expression. Furthermore, hutG, which specifies N-formylglutamate amidohydrolase, was regulated by the hutC product when the two genes were cloned on the same vector and expressed in E. coli. Therefore, hutG can be expressed independently from its own promoter, in keeping with earlier observations that N-formylglutamate amidohydrolase synthesis is not coordinated with that of urocanase and histidase and can be induced by N-formylglutamate or urocanate.
J Bacteriol 1988 Sep
PMID:Organization and multiple regulation of histidine utilization genes in Pseudomonas putida. 284 9

The effect of chemical modification on the pseudocholinesterase and aryl acylamidase activities of purified human serum pseudocholinesterase was examined in the absence and presence of butyrylcholine iodide, the substrate of pseudocholinesterase. Modification by 2-hydroxy-5-nitrobenzyl bromide, N-bromosuccinimide, diethylpyrocarbonate and trinitrobenzenesulfonic acid caused a parallel inactivation of both pseudocholinesterase and aryl acylamidase activities that could be prevented by butyrylcholine iodide. With phenylglyoxal and 2,4-pentanedione as modifiers there was a selective activation of pseudocholinesterase alone with no effect on aryl acylamidase. This activation could be prevented by butyrylcholine iodide. N-Ethylmaleimide and p-hydroxy-mercuribenzoate when used for modification did not have any effect on the enzyme activities. The results suggested essential tryptophan, lysine and histidine residues at a common catalytic site for pseudocholinesterase and aryl acylamidase and an arginine residue (or residues) exclusively for pseudocholinesterase. The use of N-acetylimidazole, tetranitromethane and acetic anhydride as modifiers indicated a biphasic change in both pseudocholinesterase and aryl acylamidase activities. At low concentrations of the modifiers a stimulation in activities and at high concentrations an inactivation was observed. Butyrylcholine iodide or propionylcholine chloride selectively protected the inactivation phase without affecting the activation phase. Protection by the substrates at the inactivation phase resulted in not only a reversal of the enzyme inactivation but also an activation. Spectral studies and hydroxylamine treatment showed that tyrosine residues were modified during the activation phase. The results suggested that the modified tyrosine residues responsible for the activation were not involved in the active site of pseudocholinesterase or aryl acylamidase and that they were more amenable for modification in comparison to the residues responsible for inactivation. Two reversible inhibitors of pseudocholinesterase, namely ethopropazine and imipramine, were used as protectors during modification. Unlike the substrate butyrylcholine iodide, these inhibitors could not protect against the inactivation resulting from modification by 2-hydroxy-5-nitrobenzyl bromide, N-bromosuccinimide and trinitrobenzenesulfonic acid. But they could protect against the activation of pseudocholinesterase and aryl acylamidase by low concentrations of N-acetylimidazole and acetic anhydride thereby suggesting that the binding site of these inhibitors involves the non-active-site tyrosine residues.
Eur J Biochem 1985 Sep 02
PMID:Chemical modification of the bifunctional human serum pseudocholinesterase. Effect on the pseudocholinesterase and aryl acylamidase activities. 286 42

Analytical gel permeation chromatography on both Sephadex and polyacrylamide columns shows that Clostridium oroticum dihydroorotase (L-5,6-dihydroorotate amidohydrolase, EC 3.5.2.3) undergoes a large decrease in molecular size when the pH is decreased from 8 to 6. The Stokes radius decreases from about 40 A to 36 A. Neither the molecular size nor kinetic properties are dependent on protein concentration. Thus, the decreased molecular size reflects a pH dependent isomerization of the enzyme.
Biochim Biophys Acta 1985 Sep 20
PMID:Evidence for a pH-dependent isomerization of Clostridium oroticum dihydroorotase. 286 82

The cell wall degradation products released from Escherichia coli during autolysis triggered by cephaloridine or trichloroacetic acid were isolated and characterized. Murein was selectively lost from the disaccharide tetrapeptides and the bisdisaccharide tetrapeptide components. Two major autolytic products accounted for more than 85% of the released material. Compound 1 (60 to 80% of released material) was a disaccharide tetrapeptide monomer containing a 1,6-anhydromuramic acid residue. Compound 2 (15 to 30% of released material) was a mixture of a tritripeptide and a tritetrapeptide without hexosamines. Taken together the findings suggest that autolytic cell wall degradation in E. coli is selective and involves the activity of both the hydrolytic transglycosylase and an endopeptidase. Upon release, at least some of the wall components were also exposed to the activity of the N-acetylmuramic acid-L-alanine amidase.
J Bacteriol 1986 Sep
PMID:Transglycosylase and endopeptidase participate in the degradation of murein during autolysis of Escherichia coli. 287 60

A common two-allele MspI restriction fragment length polymorphism of the human erythroid porphobilinogen (PBG)-deaminase gene was investigated in 33 unrelated patients with acute intermittent porphyria (AIP) and 20 controls. The polymorphism was tightly linked (lod score 3.14; no recombinants) to the locus for AIP as identified by measurement of erythrocyte PBG-deaminase activity. The frequency of the polymorphism in the AIP patients did not differ significantly from that in the controls. No common polymorphisms for eight other restriction endonucleases were found in either group. In 30 of the AIP patients no crossreacting immunological material (CRIM) was produced by the mutant PBG-deaminase allele. The MspI polymorphism enabled each PBG-deaminase allele to be distinguished in subjects heterozygous for the polymorphism; thus a major gene deletion was excluded as the cause of the CRIM-negative mutation in all of the 18 families that contained an affected CRIM-negative individual heterozygous for the polymorphism. In suitable families, the MspI polymorphism provides a more certain way of identifying carriers of the AIP gene than current enzymatic methods and major gene deletions are unlikely to be present in more than a small proportion of the commonest type of AIP, the CRIM-negative form.
Lancet 1987 Sep 26
PMID:DNA polymorphism of human porphobilinogen deaminase gene in acute intermittent porphyria. 288 41

A phage-associated murein hydrolase activity (PAL) induced in an autolysis-defective mutant of Streptococcus pneumoniae infected with the bacteriophage Dp-1 has been recently isolated and purified to electrophoretic homogeneity as well as biochemically characterized as an endo-N-acetyl-muramyl-L-alanine amidase (1, 3, 4). The PAL and the inactive form (E-form) of the host cell autolysin show a remarkable biochemical similarity, although they differ in their immunological characteristics. The PAL was adsorbed onto a live, defective mutant of pneumococcus (cwl) and such cells reverted to the wild type phenotype ("cured" cells) in some important characteristics present in the wild type strain (R6), as: i) lysis of the culture in the stationary phase, ii) protoplast formation by hypertonic sucrose, and iii) bacteriolytic response against the penicillin in contrast with the bacteriostatic response of the "non-cured" cwl. The adsorbed enzyme segregates during growth of the "cured" cells. Our results demonstrate that PAL acts in the phenotypically "cured" cells in a similar way to that previously described for the host enzyme, and also confirm the finding that the autolysins play a direct role in the irreversible effects produced in S. pneumoniae by the betalactamic antibiotics.
Microbiologia 1985 Sep
PMID:[Phenotypical curing of Streptococcus pneumoniae treated with amidase induced by the Dp-1 bacteriophage]. 290 22

Porphobilinogen deaminase has been purified and crystallized from an overproducing recombinant strain of Escherichia coli harbouring a hemC-containing plasmid which has permitted the purification of milligram quantities of the enzyme. Determination of the Mr of the enzyme by SDS/polyacrylamide-gel electrophoresis (35,000) and gel filtration (32,000) agrees with the gene-derived Mr of 33,857. The enzyme has a Km of 19 +/- 7 microM, an isoelectric point of 4.5 and an N-terminal sequence NH2-MLDNVLRIAT. The substrate, porphobilinogen, binds to the active-site dipyrromethane cofactor to form three intermediate complexes: ES, ES2 and ES3. The gene-derived primary structure of the E. coli deaminase is compared with that derived from the cDNA of the human enzyme.
Biochem J 1988 Sep 01
PMID:Purification, crystallization and properties of porphobilinogen deaminase from a recombinant strain of Escherichia coli K12. 305 34


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>