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

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Query: EC:1.6.99.3 (diaphorase)
5,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Carcinomas of the ethmoidal region of the nose are observed relatively frequently in cattle in several countries in tropical and subtropical latitudes. Viruses have been implicated as causative agents, but it has been observed that affected animals sometimes suffer from aflatoxicosis, and a role of aflatoxin B1 (AFB1) in the aetiology has also been proposed. We have examined whether the bovine nasal olfactory mucosa has a capacity to metabolize AFB1. The contents of cytochrome P-450 and cytochrome b5, and the NADPH cytochrome c reductase activity in the nasal olfactory mucosa have also been determined. Comparative experiments have been performed with the liver. Incubations with 3H-labelled AFB1 showed that the nasal olfactory mucosa has a much higher capacity than the liver to form lipid-soluble, water-soluble and tissue-bound AFB1-metabolites. High-resolution microautoradiography showed a strong localization of tissue-bound metabolites in the sustentacular cells in the apical portion of the olfactory surface epithelium and in Bowman's glands in the olfactory lamina propria mucosae. Especially in the sustentacular cells the labelling was preferentially located in the nuclei of the cells. Liquid chromatography of chloroform extracts of the nasal olfactory mucosa and the liver incubated with 3H-AFB1 showed formation of several metabolites. The dominating peak in both tissues was aflatoxin M1 (AFM1). However, the amount of AFM1 was higher in the nasal olfactory mucosa than in the liver, and the amounts and proportions of several other metabolites also differed markedly between the two tissues. The level of cytochrome P-450 in the nasal olfactory mucosa was found to be about one quarter of that in the liver, but the NADPH cytochrome c reductase activity was much higher in the nasal olfactory mucosa than in the liver. In addition, the cytochrome b5: cytochrome P-450 ratio was higher in the nasal olfactory mucosa than in the liver. The higher metabolism of AFB1 in the nasal olfactory mucosa than in the liver may be related to differences in the cytochrome P-450 isoenzyme profile. In addition, the microsomal electron transport to cytochrome P-450 may be facilitated by the high reductase: cytochrome P-450 ratio and the high cytochrome b5: cytochrome P-450 ratio in the nasal olfactory mucosa.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Metabolism of aflatoxin B1 in the bovine olfactory mucosa. 249

The bovine mitochondrial gene products ND2 and ND4, components of NADH dehydrogenase, have been purified from a chloroform/methanol extract of mitochondrial membranes, and the human mitochondrial gene products ND2 and cytochrome b have been obtained by similar procedures. They have been identified by comparison of their amino-terminal protein sequences with those predicted from DNA sequences of bovine and human mitochondrial DNA. All of the proteins have methionine as their amino-terminal residue. In bovine ND2, this residue is encoded by the "universal" isoleucine codon AUA, and the sequences of human cytochrome b and bovine ND2 demonstrate that AUA also encodes methionine in the elongation step of mitochondrial protein synthesis. In human ND2, the amino-terminal methionine is encoded by AUU, which, as in the "universal" genetic code, is also used as an isoleucine codon in elongation. Thus, AUU has a dual coding function which is dependent upon its context.
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PMID:Initiation codons in mammalian mitochondria: differences in genetic code in the organelle. 296 65

The hepatotoxicity of chloroform (CHCl3) is thought to require biotransformation, by the polysubstrate monooxygenase system (P-450), to a reactive intermediate(s). Therefore, the potentiation of CHCl3-induced hepatotoxicity, which occurs following exposure to certain ketones, may hypothetically be explained by a reduced capacity of the cell to form glutathione conjugates (detoxicate the intermediate) and (or) by an increased rate of reactive intermediate(s) generation secondary to a modification of the P-450 system. To test these hypotheses, liver damage, as indicated by elevation in plasma alanine aminotransferase and ornithine carbamyl transferase activities, was modulated in male Sprague-Dawley rats by varying the time interval (10, 18, 24, 48, 72, 96 h) between acetone, 2-butanone, or 2-hexanone (15 mmol/kg, p.o.) pretreatment and CHCl3 (0.5 mL/kg, p.o.) administration. These data were compared with hepatic glutathione and with various parameters of the polysubstrate monooxygenase system: cytochrome P-450, cytochrome c reductase, cytochrome b5, and microsomal binding of 14CHCl3-derived radiolabel. Reduced detoxication capacity does not appear to be involved as hepatic glutathione levels were not reduced. Globally, a relationship between modifications to the polysubstrate monooxygenase system and potentiation of CHCl3-induced hepatotoxicity appears to exist. The rank order of each ketone's ability to modify P-450 parameters was the same in most instances as that based on peak ability to potentiate CHCl3-induced hepatotoxicity: 2-hexanone greater than 2-butanone greater than or equal to acetone. Therefore, these results suggest that a general relationship exists between the ketone-induced potentiation of CHCl3-induced hepatotoxicity and increased CHCl3 reactive metabolite generation. However, other factors may also contribute to the phenomenon.
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PMID:The role of biotransformation-detoxication in acetone-, 2-butanone-, and 2-hexanone-potentiated chloroform-induced hepatotoxicity. 344 91

The ability of S-9 fractions isolated from the livers of 4-, 12-, and 26-month-old male inbred F344 rats to activate and metabolize the hepatocarcinogen aflatoxin B1 [(AFB1) CAS: 1162-65-8] was studied. The following observations were made: The activation of AFB1 to compounds that are mutagenic in the Ames Salmonella-microsome test and to compounds that covalently bind DNA in vitro was similar for liver S-9 from 4- and 12-month-old rats. A 30-50% decrease in the activation of AFB1 occurred in rats between 12 and 26 months of age. The in vitro metabolism of AFB1 to chloroform-soluble and water-soluble metabolites was similar for 4- and 12-month-old rats and decreased significantly in rats after 12 months of age. The proportion of most of the chloroform-soluble metabolites of AFB1 formed by liver S-9 from 4-, 12-, and 26-month-old rats was similar. However, the proportion of aflatoxicol (CAS: 29611-03-8) produced by liver S-9 increased approximately twofold in rats between 12 and 26 months of age. The cytochrome P450 content and the NADPH cytochrome c reductase activity of liver microsomes decreased 40-45% in rats between 12 and 26 months of age. However, the activities of UDPglucuronyltransferases and most forms of glutathione S-transferase did not change significantly with increasing age in liver microsomes and cytosol, respectively.
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PMID:Metabolism, covalent binding, and mutagenicity of aflatoxin B1 by liver extracts from rats of various ages. 391 13

The binding of [14C]dicyclohexylcarbodiimide (DCCD) to soluble complex III from yeast mitochondria was examined under conditions which resulted in the inhibition of proton ejection but had a minimal effect on cytochrome c reductase activity. Incubation of the complex with 50-100 nmol of [14C]DCCD/nmol of cytochrome b at 12 degrees C did not result in any changes in the appearance of the high-molecular-weight subunits (I-V) after sodium dodecyl sulfate-gel electrophoresis, although a slight broadening of the three lowest molecular-weight subunits (VI-VIII) was observed. The [14C]DCCD was bound preferentially to subunit III (cytochrome b) and a wide band with an apparent low-molecular weight ranging from 8000 to 9000 to less than 2000 depending on the gel system used. Extraction of the [14C]DCCD-treated complex III with chloroform:methanol had no effect on subunit III but completely removed the low-molecular-weight radioactive band. Thin-layer chromatography of the chloroform:methanol extract revealed that the radioactive material extracted from the [14C]DCCD-treated complex III migrated with the same apparent RF as either free [14C]DCCD or cardiolipin. Amino acids were not detectable in an acid hydrolysate of the chloroform:methanol extract, suggesting the absence of protein. Digestion of the [14C]DCCD-treated complex III with either chymotrypsin or Staphylococcus aureus V8 protease resulted in the decrease of both staining intensity and labeling in subunit III but had no effect on the radioactivity in the low-molecular-weight material. These results confirm that DCCD binds preferentially to cytochrome b in complex III from yeast mitochondria and suggest that cytochrome b may play an important role in proton translocation at this site of the respiratory chain.
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PMID:The preferential binding of dicyclohexylcarbodiimide to cytochrome b and phospholipids in soluble complex III from yeast mitochondria. 608 3

2-Hexanone (2-Hx) is known to potentiate chloroform (CHCl3) hepatotoxicity in part by increasing the bioactivation of CHCl3 to phosgene (COCl2). Treatment of rats with 2-Hx + CHCl3 in vivo did not initiate peroxidation of hepatic fatty acids as determined by formation of conjugated dienes or depletion of unsaturated fatty acids, or as determined by production of malondialdehyde (MDA) in vitro. A 5-fold decrease in the specific activity of succinate-dependent cytochrome c reductase in liver from rats treated in vivo with corn oil (vehicle) + CHCl3 and in rats treated with 2-Hx + CHCl3 indicated that a mechanism independent of CHCl3 bioactivation may add to the hepatotoxic effects which result from the metabolism of chloroform to phosgene.
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PMID:Mechanisms in 2-hexanone potentiation of chloroform hepatotoxicity. 609 Dec 97

A nonproteinaceous, antimycin A insensitive ubiquinol-cytochrome c reductase activity is detected in and purified from chromatophores of Rhodopseudomonas sphaeroides, R-26. This activity is about 5 times the antimycin A sensitive reductase activity in chromatophores and the two are not interconvertable. The purification involved chloroform:methanol (2:1), and hexane extractions and florisil column chromatography. The purified preparation contains some bacteriochlorophyll-like pigments and phospholipids, and is stable in organic solvent. It catalyzes the oxidation of ubiquinol by cytochrome c with substrate specificity and pH optimum.
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PMID:The existence of an antimycin A insensitive ubiquinol-cytochrome c reductase activity in the photosynthetic apparatus. 630 19

A rapid, precise, and accurate photometric method for determining free and esterified fecal 3 alpha-hydroxy bile acids is described. Feces are homogenized and (a) extracted with boiling absolute ethanol, or (b) lyophilized and extracted with chloroform:methanol 2:1 (v/v). Hydrolyzed and nonhydrolyzed crude extracts are prepared and aliquots treated with a reagent containing nitro blue tetrazolium (NBT), 3 alpha-hydroxysteroid oxidoreductase, beta-nicotinamide adenine dinucleotide (beta-NAD) and diaphorase. The reagent first oxidizes bile acid 3 alpha-hydroxyls to 3-oxo groups and 3 beta-hydrogen is transferred to beta-NAD yielding beta-NADH. beta-NADH in turn reduces NBT (yellow) to its diformazan (blue). Absorbance is measured at 540 nm and is proportional to the 3 alpha-hydroxy bile acid titer of fecal extract aliquots. Fecal pigments present in crude extracts do not interfere with the assay since they absorb minimally at 540 nm.
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PMID:Rapid photometric determination of free and esterified 3 alpha-hydroxy fecal bile acids. 666 19

2,5-Hexanedione (2,5-HD) pretreatment potentiated CHCl3-induced hepatotoxicity. 2,5-HD significantly increased hepatic cytochrome P-450, NADPH cytochrome c reductase, aniline hydroxylation, p-nitroanisole O-demethylation, and aminopyrine N-demethylation in both male and female mice. 2,5-HD pretreatment potentiated CHCl3-induced centrilobular necrosis and increased serum alanine amino transferase (ALT) activity by 20 times more than CHCl3 alone. Similarly, 2,5-HD pretreatment potentiated CDCl3-induced hepatotoxicity as well as CCl4-induced hepatotoxicity in male mice, but did not potentiate trichloroethylene-, 1,1,2-trichloroethane-, or perchloroethylene-induced hepatotoxicity. In female mice, 2,5-HD pretreatment potentiated CHCl3- and CDCl3-induced hepatotoxicity as well as trichloroethylene-, 1,1,2-trichloroethane-, and carbon tetrachloride-induced hepatotoxicity, but not perchloroethylene-induced hepatotoxicity. 2,5-HD pretreatment had no preferential effect on either CHCl3- or CDCl3-induced hepatotoxicity in females. However, phenobarbital pretreatment did differentiate CHCl3- and CDCl3-induced hepatotoxicity in females. 2,5-HD-induced potentiation of halocarbon hepatotoxicity is sex dependent.
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PMID:Role of biotransformation in the potentiation of halocarbon hepatotoxicity by 2,5-hexanedione. 712 May 9

Atherosclerosis is a basis of development for many cardiovascular diseases, which are leading causes of death among people in the 21-st century. One of possible causes of atherosclerosis may be somatic mutations of human mitochondrial genome. In order to identify mutations associated with atherosclerosis, we analyzed 42 mitochondrial mutations found in various pathologies. The subject of the study were individuals who died as a result of an accident or a sudden death. The material for the investigation were segments of intima from 7 aortas both normal and with lipofibrous plaques. DNA was isolated by a method of phenol-chloroform extraction. PCR-fragments of DNA containing the region of investigated mutations were analyzed by an original method of quantitative assessment of mitochondrial genome mutant alleles. This method was developed in our laboratory on the basis of pyrosequencing technology. Statistical data processing was performed using IBM SPSS Statistics 21.0 and by bootstrap analysis. 40 of 42 studied mutations were heteroplasmic and two were homoplasmic according to the absence of a mutant allele in atherosclerosis. The developed method of direct quantitative assessment of mitochondrial genome mutant alleles helped us to find three new mutations: 652delG, 961delC and 5132insAA. It was found that 11 of mitochondrial mutations (652insG, T3336S, C3256T, G14459A, G14846A, G15059A, 652delC, A1555G, C5178A, G13513A and G12315A), belonging to eight mitochondrial genes: rRNA 12S, tRNA - Leu (codon recognition UUR) and tRNA - Leu (codon recognition CUN), subunit 1, 2, 5 and 6 of NADH dehydrogenase and cytochrome B are potentially associated with atherosclerosis, because from 29% (2 of 7 aortas) to 86% (6/7) investigated aortas have a significant difference in the heteroplasmy level of these mutations in lipofibrous plaques compared to normal aortic intima.
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PMID:[Association of mitochondrial genome mutations with lipofibrous plaques in human aortic intima]. 2622 85


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