Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.99.3 (diaphorase)
5,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dietary protein deficiency is known to modify the response to the pharmacotoxicological activities of drugs and foreign compounds, due in part to altered rates of metabolism. Prediction of whether in vivo susceptibilities to foreign compounds are increased or decreased in protein deficient animals has been said to be related to the relative toxicites of the metabolic products. We have shown that weanling rats fed semipurified casein diets for 15 days show a 75% depression of hepatic microsomal mixed function oxidase activities. About one-fourth of this decrease is due to a retardation of the normal rate of liver cell proliferation and less microsomal protein; the remaining three-fourths is due to a reduction of the specific enzyme activity. This latter decrease is closely correlated with similar decreases in cytochrome P-450 and cytochrome c reductase activities and cytochrome P-450 contents. Although protein deficiency affects the relative contents of phosphatidylcholine and cytochrome P-450, this does not result in modifications of the Km for metabolism, as is seen with phenobarbital administration in the various dietary groups. The depression of mixed function oxidase enzyme activities caused by feeding the protein deficient diet for 15 days can be restored to normal by feeding the 20% casein diets for an additional 30 days in the case of aniline hydroxylase but only partially in the case of ethylmorphine N-demethylase. The complexities of determining the role of metabolism as a modulator of protein deficiency effects on foreign compound toxicity are discussed.
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PMID:The effect of quantity and quality of dietary protein on drug metabolism. 97 91

Adult rats of either sex and mature females ovariectomized 44 days earlier, were partially hepatectomized under ether anesthesia, leading to two-thirds organ removal. The respective controls were incised and the livers manipulated by hand. At specified p.o. periods, hepatic microsomal total protein, cytochrome P-450 and activities of the enzymes, aminopyrine demethylase and benzo[a]pyrene hydroxylase were determined for the respective pairs and submitted to analysis of variance. The data are expressed as ratios of the sham-operated to the partially hepatectomized group mean values on a percentage basis. For one male series, cytochrome P-450 and the 2 enzyme activities were significantly elevated with the intact rats at 72 and 96 h and 10 days and in yet another series of the same sex, the findings were similar except that only the cytochrome level of the controls was increased at day 10; the ratios normalized by day 21. As screened in a few groups, the changes in microsomal NADPH cytochrome c reductase were not noteworthy. Possible latency periods were shorter for the female series and the hydroxylase activity was elevated in the intact liver microsomes over test periods of 24 h to 10 days. In general, although a trend of increased parameter value for the intact group was apparent and in agreement with several published reports, statistical significance could not be substantiated in many instances, wide variations and sporadic data being encountered. None of the intact group changes in the constants were significant with the ovariectomized series. The effect of an inducer, phenobarbital, was determined in relation to the 10 day-ratios derived for males fed a casein based control diet as such and supplemented with 30 wt % each of glucose, fructose, galactose, maltose and lactose, the last one being screened only in partially hepatectomized rats. Phenobarbital was injected i.p. daily at 80 mg/kg on the last 3 days. Among other changes noted with the respective ratios, each of the intact groups displayed remarkable elevations in the total protein content. Additional comparisons are also advanced for the individual group parameter findings in relation to the control diet- and the 30% glucose-fed animals.
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PMID:Variations in microsomal parameters of intact and regenerating rat liver with time and on feeding high carbohydrate diets. 235 31

Mammary explants from pregnant rats can be induced in regard to casein synthesis and alpha-lactalbumin activity when cultured in the presence of hydrocortisone, prolactin and levels of insulin approaching physiological concentrations. No detectable induction occurs in the absence of insulin. Although epidermal growth factor and multiplication stimulating activity, in the presence of hydrocortisone, can maintain the initial level of NADH-cytochrome c reductase as well as insulin, neither can substitute effectively for insulin in the induction of the milk proteins. Proinsulin, nerve growth factor, platelet-derived growth factor and fibroblast growth factor are also ineffective substitutes for insulin in this regard. Whereas prolonged tissue exposure to multiplication stimulating activity, hydrocortisone and prolactin does not result in induction of alpha-lactalbumin activity, subsequent addition of insulin leads to prompt response. The results suggest that the ability of insulin to function as a unique, essential factor in the induction of rat milk proteins is independent of its cell-maintenance activity. Thus, in addition to its well established functions in metabolic processes, insulin appears to play a vital role in certain developmental processes.
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PMID:A unique and essential role for insulin in the phenotypic expression of rat mammary epithelial cells unrelated to its function in cell maintenance. 635 73

The differentiative functions, lactose synthetase activity and casein synthesis, can be induced in mammary gland explants from intact mice when insulin, cortisol, and PRL are present in the medium. By contrast, the tissue from mice castrated for 1--2 months does not differentiate in vitro. Explants from these ovariectomized animals retain their sensitivity toward insulin, as evidenced by the ability of this hormone to stimulate DNA synthesis, alpha-aminoisobutyric acid accumulation, and glucose-6-phosphate/gluconate-6-phosphate dehydrogenase activities. This tissue also remains sensitive to cortisol, as evidenced by the ability of this steroid to stimulate NADH-cytochrome c reductase activity. However, the tissue from ovariectomized mice has lost biological responsiveness to PRL. Such insensitivity may be due to a deficiency of PRL receptors, which are reduced in the glands from castrated mice to 20--25% of control values. However, a second defect between the receptor and the genome is also likely, since PRL unresponsiveness is still present in the tissue of ovariectomized animals whose mammary PRL-binding has been partially maintained by elevating serum PRL levels with a pituitary transplant. Therefore, this system may be useful for the study of cellular processes related to PRL action beyond the receptor level.
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PMID:Loss of differentiative potential of the mammary gland in ovariectomized mice: identification of a biochemical lesion. 678 89

Nitrate reductase from the yeast Candida nitratophila was found to contain one molecule of cytochrome b557 and one atom of molybdenum per subunit. FAD/haem-dependent diaphorase activity (haem domain) was associated with a 40 kDa tryptic fragment of the subunit. The 50 amino-terminal residues of this fragment were determined, and the sequence did not show significant similarity to deduced sequences of other nitrate reductases previously published. Increasing ionic strength in vitro had a stimulatory effect on enzymic activity via stimulation of the molybdenum-dependent terminal nitrate-reducing activity. Stimulation of activity by exogenous protein (bovine serum albumin or casein) also appeared to be an ionic effect. Stimulation of catalytic activity by phosphate was a separate effect.
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PMID:Further characterization of the assimilatory nitrate reductase from the yeast Candida nitratophila. 847 56

Both mitochondrial and nuclear gene sequences have been employed in efforts to reconstruct deep-level phylogenetic relationships. A fundamental question in molecular systematics concerns the efficacy of different types of sequences in recovering clades at different taxonomic levels. We compared the performance of four mitochondrial data sets (cytochrome b, cytochrome oxidase II, NADH dehydrogenase subunit I, 12S rRNA-tRNA-16S rRNA) and eight nuclear data sets (exonic regions of alpha-2B adrenergic receptor, aquaporin, ss-casein, gamma-fibrinogen, interphotoreceptor retinoid binding protein, kappa-casein, protamine, von Willebrand Factor) in recovering deep-level mammalian clades. We employed parsimony and minimum-evolution with a variety of distance corrections for superimposed substitutions. In 32 different pairwise comparisons between these mitochondrial and nuclear data sets, we used the maximum set of overlapping taxa. In each case, the variable-length bootstrap was used to resample at the size of the smaller data set. The nuclear exons consistently performed better than mitochondrial protein and rRNA-tRNA coding genes on a per-residue basis in recovering benchmark clades. We also concatenated nuclear genes for overlapping taxa and made comparisons with concatenated mitochondrial protein-coding genes from complete mitochondrial genomes. The variable-length bootstrap was used to score the recovery of benchmark clades as a function of the number of resampled base pairs. In every case, the nuclear concatenations were more efficient than the mitochondrial concatenations in recovering benchmark clades. Among genes included in our study, the nuclear genes were much less affected by superimposed substitutions. Nuclear genes having appropriate rates of substitution should receive strong consideration in efforts to reconstruct deep-level phylogenetic relationships.
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PMID:Mitochondrial versus nuclear gene sequences in deep-level mammalian phylogeny reconstruction. 1115 72

A nitrate reductase (EC 1.6.6.1)-inactivating factor has been isolated from 8-day-old wheat leaves. The purification schedule involved ammonium sulfate precipitation, Sephadex G-100 filtration, DEAE-cellulose chromatography, and Sephadex G-150 filtration. No accurate assessment could be made as to the degree of purification relative to crude extract as the inactivating factor could not be detected in crude extract. However a 2,446-fold purification was achieved from the ammonium sulfate fraction to the pooled enzyme from the Sephadex G-150 step.The inactivating factor was heat-labile and had a molecular weight of 37,500. The inactivating factor was particularly sensitive to the divalent metal chelators, 1,10-phenanthroline and bathophenanthroline. Evidence indicated that Fe(2+) may be the functional metal. The trypsin inhibitors N-alpha-p-tosyl-l-lysine chloromethyl ketone and alpha-N-benzoyl-l-arginine were inhibitory. However, phenylmethyl sulfonyl fluoride, an inhibitor of serine peptide hydrolases, was not inhibitory. Neither casein nor hemoglobin nor a range of artificial substrates were hydrolyzed by the inactivating factor. Highly purified wheat leaf nitrite reductase (EC 1.7.99.3) and ribulose 1,5-bisphosphate carboxylase:oxygenase (EC 4.1.1.39) were not affected by the nitrate reductase-inactivating factor.The inactivating factor was more active toward the NADH-nitrate reductase compared to either of the component enzymic activities flavin adenine mononucleotide-nitrate reductase and methyl viologen-nitrate reductase. The NADH-ferricyanide reductase (diaphorase) component was the least sensitive.
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PMID:In Vitro Stability of Nitrate Reductase from Wheat Leaves: III. Isolation and Partial Characterization of a Nitrate Reductase-inactivating Factor. 1666 Oct 24

A bush-type plant was selected from tropical pumpkin 'cga' (Cucurbita moschata Duchesne) in order to study the vine development in C. moschata. In this study, a novel gene encoding NADH dehydrogenase was isolated from the vine line (cgaV) of C. moschata, that was not expressed in the near isogenic bush line (cgaBu). This gene, designated as CmV1 (C. moschata vine 1), was 545 bp in length and was composed of a 477 bp open reading frame, which had 99% nucleotide similarity to the chloroplast ndhJ gene for NADH dehydrogenase subunit J from Brassica oleracea. The deduced amino acid sequence of CmV1 had 99% similarity to NADH dehydrogenase subunit J from Arabidopsis and had 98% similarity to NADH dehydrogenase subunit from Barbarea verna. Analysis of the basic characteristics of the CmV1 protein revealed that it has one Respiratory chain NADH dehydrogenase 30 kD subunit signature, three N-myristoylation sites, one Casein kinase II phosphorylation site, and one Protein kinase C phosphorylation site. Reverse transcriptase-PCR analysis showed that CmV1 was expressed at a high level in the internodes and hypocotyls and was expressed stronger in elongating internodes than in fully expanded internodes. In conclusion, results obtained in the present study suggest that CmV1 gene might play important roles in vine elongation of tropical pumpkin.
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PMID:Molecular cloning and expression of a bush related CmV1 gene in tropical pumpkin. 1930 73