Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.5.1.4 (deaminase)
5,113 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The metabolism of fungicide benzoic acid, 1,3-dithiolan-2-ylidenehydrazied (Yekuling) was studied quantitatively in rat liver microsomes and liver soluble fractions pretreated with phenobarbital (PB) and 3-methylcholanthrene (3-MC) by high pressure liquid chromatography. The experimental results indicated that the major metabolic pathway of Yekuling in vitro was hydrolysis. PB can enhance amidase activity to increase formation of benzoic acid and 1,3-dithiolan-2-ylidenehydrazine. 3-MC treatment elevated rat liver microsomal cytochrome P-448, enhancing S-oxidation of Yekuling. On the other hand, S-oxidation of Yekuling by rat liver microsomal MFO was NADPH-dependent.
...
PMID:[Studies on metabolism of fungicide benzoic acid, 1,3-dithiolan-2-ylidenehydrazide in vitro]. 130 96

Methemoglobinemia produced by exposure to the herbicide propanil (3,4-dichloropropionanilide) is thought to be mediated by toxic metabolites formed during the hepatic clearance of the parent compound. We examined the metabolism of propanil and 3,4-dichloroaniline in rat liver microsomes to identify metabolites that may be involved in propanil-induced methemoglobinemia. The major pathway of propanil metabolism in microsomal incubations was acylamidase-catalyzed hydrolysis to 3,4-dichloroaniline. The reaction did not require NADPH, and was inhibited by the acylamidase inhibitors paraoxon and sodium fluoride. Oxidized metabolites were isolated by high-performance liquid chromatography, and identified as 2'-hydroxypropanil and 6-hydroxypropanil by comparison of their mass and nuclear magnetic resonance spectra to those of synthetic standards. Major microsomal metabolites of 3,4-dichloroaniline were 6-hydroxy-3,4-dichloroaniline and N-hydroxy-3,4-dichloroaniline. Both N-hydroxy-3,4-dichloroaniline and 6-hydroxy-3,4-dichloroaniline directly oxidized hemoglobin in rat erythrocyte suspensions in a concentration-dependent manner; however, the potency of N-hydroxy-3,4-dichloroaniline was at least an order of magnitude greater than that of 6-hydroxy-3,4-dichloroaniline.
...
PMID:Metabolism of the arylamide herbicide propanil. I. Microsomal metabolism and in vitro methemoglobinemia. 231 34

This communication presents the results obtained in tubular aggregates of 24 enzyme histochemical techniques for demonstrating activity of oxidoreductases, transferases, hydrolases and isomerases. The activity characteristics of the tubular aggregates in m. gluteus medius of 18 patients with diseases of the neuromuscular system were almost identical. A high activity of the mitochondrial enzymes, NADPH: tetrazolium oxidoreductase, NADH:tetrazolium oxidoreductase and cytochrome c oxidase, could be shown in the pathological structures, whereas the activity of the mitochondrial enzymes, glycerol-3-phosphate:menadione oxidoreductase, succinate:PMS oxidoreductase, malate:NAD+ oxidoreductase and isocitrate:NAD+ oxidoreductase, and the partial mitochondrial enzymes, malate:NADP+ oxidoreductase and isocitrate:NADP+ oxidoreductase, was very slight or even absent. There was a moderate to strong activity of the glycolytic enzymes lactate:NAD+ oxidoreductase, glyceraldehyde-3-phosphate:NAD+ oxidoreductase, phosphofructokinase, phosphoglucomutase and glucose phosphate isomerase. In contrast, the activity of alpha-glucan phosphorylase was slight. The activity of phosphogluconate:NADP+ oxidoreductase, glucose-6-phosphate:NADP+ oxidoreductase and 5'-nucleotidase was slight, whereas there was no activity of myosin ATPase and mitochondrial ATPase, acid phosphatase or alkaline phosphatase. The high activity of AMP-deaminase was very striking. The activity of peroxidase was moderate. Results obtained with adsorption studies point to adsorption of some of the enzymes studied to the tubular aggregates in vivo and this phenomenon very probably determined the histochemical characteristics of these structures.
...
PMID:Histochemical features of tubular aggregates in diseased human skeletal muscle fibres. 317 98

Porphorbilinogen oxygenase (EC 4.2.1.24) was associated with the microsomal fraction of bone marrow in normal rats and in rats submitted to erythropoietic stress, while porphobilinogen deaminase (EC 4.3.1.8) of the same origin was present in the cytosol. An NADPH-dependent electron-donor system for the oxygenase was also present in the microsomes of the bone marrow. Under conditions of erythropoietic stress caused by hypoxia, the activities of both enzymes were found to be inversely correlated. While the oxygenase showed minimum activity between the 4th and 8th day of hypoxia, porphobilinogen deaminase reached its maximum activity during this period. After the 8th day of hypoxia, oxygenase activity increased while deaminase activity decreased. The NADPH-dependent electron-transport system necessary for the microsomal oxygenase activity was largely inactivated after the 10th day of hypoxia, while oxygenase activity was not affected. The particulate porphobilinogen oxygenase could be solubilized from the bone marrow microsomes with 1% deoxycholate or 0.5 M KCl. In addition, the oxygenase was also released by freezing and thawing the microsomes isolated from bone marrow of rats which had been submitted to an erythropoietic stress (hypoxia or phenylhydrazine). The enzyme solubilized with deoxycholate or KCl showed a high molecular weight form and a low molecular weight form (Mr 25 000). The former could be transformed into the latter either by treatment with 2 M KCl or by succinylation. When the oxygenase was solubilized by freezing and thawing a third molecular weight form (Mr 50 000) also appeared. The solubilized enzyme could be succinylated without loss of its catalytic activity, while the membrane-bound enzyme could not be succinylated.
...
PMID:The regulation of porphobilinogen oxygenase and porphobilinogen deaminase activities in rat bone marrow under conditions of erythropoietic stress. 369 63

Homogeneous adenylate deaminase from snail foot muscle deaminated 5'-AMP, 5'-ADP, 5'-ATP and NADH with similar velocity and affinity to all substrates. At millimolar concentration NAD+ was also deaminated to a comparable extent, but NADP+, NADPH and FAD were not substrates for the snail enzyme. The amount of deaminase activity per g of fresh tissue is 5-10 times greater than in the muscle of any other species studied. The activity of the snail deaminase is regulated by pH, KCl and buffer concentrations, and Pi; however, regulation seems to be very poor in comparison with that of muscle deaminases from other species, specific to 5'-AMP. Snail enzyme appears as the first animal deaminase so far described that has such characteristics. It offers also some opportunities as an analytical tool as a consequence of its very high affinity toward adenylates.
...
PMID:Direct deamination of AMP, ADP, ATP and NADH by non-specific adenylate deaminase in the foot muscle of the snail Helix pomatia. 662 80

Pyrimidine ribonucleoside catabolic enzyme activities of the opportunistic pathogen Pseudomonas pickettii were examined. Of the pyrimidine and related compounds tested, only dihydrouracil (nitrogen source) and ribose (carbon source) supported growth. Thin-layer chromatographic separation of the uridine and cytidine catabolities produced by P. pickettii extracts indicated that this pseudomonad contained nucleoside hydrolase activity. Its presence was confirmed by enzyme assay. Hydrolase activity was elevated in both glucose- and ribose-grown cells relative to succinate-grown cells. Nucleoside hydrolase activity was depressed when dihydrouracil served as a nitrogen source. Cytosine deaminase activity was present in extracts prepared from succinate-, glucose- or ribose-grown cells when (NH4)2SO4 served as the nitrogen source although cells grown on glucose or ribose exhibited a higher enzyme activity. Cytosine deaminase activity was not detected in extracts prepared from cells grown on dihydrouracil as a nitrogen source. Both dihydropyrimidine dehydrogenase and dihydropyrimidinase activities were measurable in P. pickettii. The dehydrogenase activity was higher with NADH than with NADPH as its nicotinamide cofactor when uracil served as its substrate. Carbon source did not affect dehydrogenase or dihydropyrimidinase activity greatly but both activities were diminished in cells grown on the nitrogen source dihydrouracil.
...
PMID:Pyrimidine ribonucleoside catabolic enzyme activities of Pseudomonas pickettii. 771 Feb 77

N-(2,6-dimethylphenyl)-5-methyl-3-isoxazolecarboxamide (D2624) belongs to a new series of experimental anticonvulsants related to lidocaine. This study was undertaken to understand the pharmacokinetics and metabolism of D2624 in rats and humans, with emphasis on the possible formation of 2,6-dimethylaniline (2,6-DMA). After oral administration of stable isotope-labeled parent drug to rats and GC/MS analysis of plasma samples, two metabolites were identified: D3017, which is the primary alcohol, and 2,6-DMA, formed by amide bond hydrolysis of either D2624 or D3017. In urine, three metabolites of D2624 were identified: namely D3017,2,6-DMA, and D3270 (which is the carboxylic acid derivative of D3017). Based on plasma AUC analysis, D3017 and 2,6-DMA accounted for > 90% of the dose of D2624. After oral administration, D2624 was found to be well absorbed (93%), but underwent extensive first-pass metabolism in the rat, thus resulting in 5.3% bioavailability. Rat and human liver microsomal preparations were capable of metabolizing D2624 to D3017 and 2,6-DMA. The formation of D3017 was NADPH-dependent, whereas 2,6-DMA formation was NADPH-independent and probably was catalyzed by amidase(s) enzymes. In a single-dose (25-225 mg) human volunteer study, the parent drug (D2624) was not detected in plasma at any dose, whereas 2,6-DMA was detected only at the two highest doses (150 and 225 mg). D3017 was detected after all doses of parent drug, with approximate dose proportionality in AUC and a half-life of 1.3-2.2 hr. The metabolic behavior observed in humans suggests there is a marked species difference in the oxidative and hydrolytic pathways of D2624.
...
PMID:Pharmacokinetics and metabolism of the novel anticonvulsant agent N-(2,6-dimethylphenyl)-5-methyl-3-isoxazolecarboxamide (D2624) in rats and humans. 901 Jun 28

The ribG gene at the 5' end of the riboflavin operon of Bacillus subtilis and a reading frame at 442 kb on the Escherichia coli chromosome (subsequently designated ribD) show similarity with deoxycytidylate deaminase and with the RIB7 gene of Saccharomyces cerevisiae. The ribG gene of B. subtilis and the ribD gene of E. coli were expressed in recombinant E. coli strains and were shown to code for bifunctional proteins catalyzing the second and third steps in the biosynthesis of riboflavin, i.e., the deamination of 2,5-diamino-6-ribosylamino-4(3H)-pyrimidinone 5'-phosphate (deaminase) and the subsequent reduction of the ribosyl side chain (reductase). The recombinant proteins specified by the ribD gene of E. coli and the ribG gene of B. subtilis were purified to homogeneity. NADH as well as NADPH can be used as a cosubstrate for the reductase of both microorganisms under study. Expression of the N-terminal or C-terminal part of the RibG protein yielded proteins with deaminase or reductase activity, respectively; however, the truncated proteins were rather unstable.
...
PMID:Biosynthesis of riboflavin: characterization of the bifunctional deaminase-reductase of Escherichia coli and Bacillus subtilis. 906 50

1. The nephrotoxicant N-(3,5-dichlorophenyl)succinimide (NDPS) underwent nonenzymatic hydrolysis to N-(3,5-dichlorophenyl)succinamic acid (NDPSA) in buffer, rat liver and kidney homogenates, and rabbit liver homogenates. 2. In the presence of NADPH, rat liver homogenates converted NDPS to NDPSA and N-(3,5-dichlorophenyl)-2-hydroxysuccinamic acid (2-NDHSA). 3. Using liver homogenates from the phenobarbital (PB)-pretreated rat, 2-NDHSA production was increased 5-fold, and the metabolites N-(3,5-dichlorophenyl)-2-hydroxysuccinimide (NDHS) and N-(3,5-dichlorophenyl)-3-hydroxysuccinamic acid (3NDHSA) were also detected. Formation of these latter metabolites was suppressed by CO or omission of NADPH. No hydroxylated metabolites were detected when NDPSA was incubated with PB-induced rat liver homogenates. 4. Oxidative metabolites were not produced when NDPS was incubated with kidney homogenates from the control or PB-pretreated rat. 5. NDHS underwent rapid hydrolysis in buffer to yield 2-NDHSA and 3-NDHSA. 6. Rabbit liver homogenates converted NDPS to NDPSA, 3,5-dichloroaniline (DCA), and succinic acid (SA). Production of DCA and SA was inhibited by the amidase inhibitor bis-p-nitrophenyl phosphate. Oxidative metabolism did not occur in rabbit tissue. 7. These experiments demonstrate that a PB-inducible form of rat liver P450 converts NDPS to NDHS, which then undergoes hydrolysis to 2-NDHSA and 3-NDHSA. An alternative route of production for 2-NDHSA and 3-NDHSA, via hydroxylation of NDPSA, does not occur. In rabbit liver NDPS metabolism was primarily amidase-mediated.
...
PMID:In vitro metabolism of the nephrotoxicant N-(3,5-dichlorophenyl)succinimide in the Fischer 344 rat and New Zealand white rabbit. 917 78

By determining the formation amount of isonicotinic acid (INA) from isonicotinic acid hydrazide (isoniazid:INH) in isolated rat hepatocytes, we were able to identify the involvement of the oxidative cleavage of the acid hydrazide. INA formation from INH increased significantly using the isolated hepatocytes prepared from rats pretreated with phenobarbital (PB), 3-methylcholanthrene (3MC), dexamethazone (DEX) and rifampicin (RIF), respectively, in comparison to the control group. On the other hand, a remarkable decrease in INA formation from INH was observed by the addition of such P450 inhibitor as metyrapone or cimetidine as well as an amidase inhibitor bis(p-nitrophenyl)phosphate (BNPP) to the isolated hepatocytes prepared from PB-pretreated rats. By further experiments using rat hepatic microsomes, the oxidative pathway of INA formation in INH metabolism was determined to be P450-dependent, since NADPH and oxygen were both essential for the oxidative pathway of INH to INA and the amount of INA formation was also significantly increased by P450 inducers. Regarding acetylisoniazid (AcINH) and isonicotinic acid amide (INAA), however, INA formation by P450 was little observed in the microsomal experiments.
...
PMID:Participation of P450-dependent oxidation of isoniazid in isonicotinic acid formation in rat liver. 958 87


1 2 Next >>

---