Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q8NEX9 (reductase)
 26,410 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Liver endoplasmic membrane contains two hemoproteins, cyt. P-450 and cyt. b5. Cytochrome P-450 catalyzes the hydroxylation of lipid-soluble compounds, while the cyt. b5 system is involved in desaturation of fatty acids. NAD(P)H and oxygen are essential components for both systems. Oxidation of ethanol to acetate in the liver, via alcohol and acetaldehyde dehydrogenases, leads to an elevated cellular NADH content. It has been proposed that oxidation of the cytosolic NADH occurs predominantly in the mitochondria via the substrate oxidation-reduction shuttle. In order to investigate the effects of elevated levels of cytosolic NADH on the state of the endoplasmic hemoprotein system, microsomes from a fatty human liver (post-ethanol intake) were isolated and studied. Microsomal cyt. b5 reductase was found to reoxidize cytoplasmic NADH directly and transfer the reducing equivalents readily to the microsomal oxidases. Addition of catalytic amounts of alcohol dehydrogenase, NAD, and ethanol to microsomes resulted in a rapid reduction of microsomal cyt. b5. These results are consistent with the proposal that the catalytic moiety of cyt. b5 reductase is exposed to the aqueous phase of the membrane and directly accepts reducing equivalents from the cytoplasm. Microsomes from fatty human liver showed an increased rate of cyt. b5 dependent desaturation of fatty acids. These findings suggest that ethanol metabolism may selectively affect the activity of one or the other microsomal hemoprotein. Thus, when the desaturase activity is low, drug metabolism by the cyt. P-450 pathway may predominate. Conversely, an increase in the desaturase level may lead to a decreased drug metabolism. This mechanism may underlie the clinical observations of drug intolerance reactions associated with alcohol intake.
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PMID:The role of microsomal cytochrome b5 in the metabolism of ethanol, drugs and the desaturation of fatty acids. 1 14

Investigation of NADP-dependent aldehyde reductase activity in mouse liver led to the finding that two distinct reductases are separable by DE52 ion exchange chromatography. Aldehyde reductase I (AR I) appears in the effluent, while aldehyde reductase II (AR II) is eluted with a salt gradient. By several procedures AR II was purified over 1100-fold from liver supernatant fraction, but AR I could be pruified only 107-fold because of its instability. The two enzymes are different in regard to pH optimum, substrate specificity, response to inhibitors, and reactivity with antibody to AR II. While both enzymes utilize aromatic aldehydes well, only AR II ACTS ON D-glucuronate, indicating that it is the aldyhyde reductase recently reported to be identical to NADP-L-gulonate dehydrogenase. The presence of two NADP-linked aldehyde reductases in liver has apparently not heretofore been reported.
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PMID:Resolution and partial characterization of two aldehyde reductases of mammalian liver. 1 91

An improved procedure for purifying aldehyde reductase is described. Utilization of Blue Dextran--Sepharose 4B and elimination of hydroxyapatite chromatography greatly improves the yield and ease of purification. Starting with 340 g of kidney tissue (two pig kidneys) approx. 50 mg of purified reductase may be routinely and reproducibly obtained. The purified reductase was used to establish the kinetic reaction mechanism of the enzyme. Initial-velocity analysis and product-inhibition data revealed that pig kidney aldehyde reductase follows an Ordered Bi Bi reaction mechanism in which NADPH binds first before D-glyceraldehyde. The limiting Michaelis constants for D-glyceraldehyde and NADPH were 4.8 +/- 0.7 mM and 9.1 +/- 2.1 micrometer respectively. The mechanism is similar to that of another monomeric oxidoreductase, octopine dehydrogenase, towards which aldehyde reductase exhibits several similarities, but differs from that of other aldehyde reductases. Phenobarbital is a potent inhibitor of aldehyde reductase, inhibiting both substrate and cofactor non-competitively (Ki = 80.4 +/- 10.5 micrometer and 66.9 +/- 1.6 micrometer respectively). Barbiturate inhibition seems to be a common property of NADPH-dependent aldehyde reductases.
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PMID:Kinetics and mechanism of action of aldehyde reductase from pig kidney. 3 57

Reductive metabolism of p-nitrobenzoate (2 mM) was studied in the isolated perfused rat liver, after acute ethanol dosing, with use of a hemoglobin-free perfusion medium. Formation of reduced metabolites under control conditions (0.3 mumol per g of liver per hr) was enhanced fivefold (1.4 mumol/g/hr) in the presence of ethanol (38 mM), thus reaching hepatic reductase activities occurring under anaerobic conditions (1.4 mumol/g/hr). Ethanol failed to increase hepatic nitro reduction when alcohol dehydrogenase was inhibited by pyrazole. Addition of acetaldehyde led to a marked stimulation of nitroreductase activity. Carbon monoxide did not influence the ethanol-mediated enhancement of nitroreductase activity but almost abolished the enhancement caused by anoxia. Reductive azo cleavage of salazosulfamide was not enhanced by ethanol. When nitrazepam was used as the substrate (1 mM) for the isolated perfused rat liver, addition of ethanol (38 mM) led to an enhanced content of 7-amino derivative in the liver and in the perfusate, whereas the formation of 7-acetylamino derivative remained unchanged. The distribution of nitrazepam in liver and perfusate was not altered by ethanol.
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PMID:Enhancement of reductive metabolism of p-nitrobenzoate and nitrazepam in isolated perfused rat liver by ethanol. 3 90

Long-chain alcohols are synthesized in the mouse preputial gland tumor (ESR-586) by NADPH:acyl-CoA oxidoreductase. In this study, a series of labeled acids was tested as substrates for the oxidoreductase in a cell-free system from the tumor, and the distribution of label into alcohols, waxes, and other products was determined. The system contained the labeled acid, an acyl-CoA-generating system, an NADPH-generating system, and tumor homogenate. The highest rates of alcohol synthesis were obtained with palmitic (16:0), heptadecanoic (17:0), stearic (18:0), myristic (14:0), elaidic (18:1 trans), and linoleic (18:2) acids, which yielded, respectively, 151, 124, 102, 76, 65, and 35 pmol alcohol/min per mg protein. Decanoic (10:0), lauric (12:0), oleic (18:1 cis), linolenic (18:3), arachidonic (20:4), and behenic (22:0) acids all gave lower activities. Acyl-CoA formation did not appear to be rate limiting with any of the substrates tested except behenic acid. In addition to the fatty alcohol product, a small amount of fatty aldehyde was formed in the system. Incorporation of the labeled fatty acids into wax esters was examined and the distribution of label between the alcohol and acid components of the waxes was determined. Incubation of [1-(14)C]palmitic acid yielded 3.4% free alcohol, 8.3% alcohol esterified in waxes, and 7.7% palmitoyl groups esterified into waxes, whereas, at the other extreme, [1-(14)C]linolenic acid yielded 0.8%, 0.6%, and 38%, respectively, into the homologous components.-Wykle, R. L., B. Malone, and F. Snyder. Acyl-CoA reductase specificity and synthesis of wax esters in mouse preputial gland tumors.
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PMID:Acyl-CoA reductase specificity and synthesis of wax esters in mouse preputial gland tumors. 3 66

Two NADPH-dependent aromatic aldehyde-ketone reductases purified from guinea pig liver catalyzed oxidoreduction of 17 beta-hydroxysteroids and 17-ketosteroids. One enzyme efficiently oxidized 5 beta-androstanes and reduced 17-ketosteroids of A/B cis configuration, whereas the other enzyme efficiently oxidized 5 alpha-androstanes and equally reduced both 5 alpha-and 5 beta-androstanes of 17-ketosteroids. However, aromatic aldehydes and ketones, and 3-ketosteroids were irreversibly reduced by the two enzymes. The two enzymes utilized NADP+ or NADPH as cofactor, but little activity with NAD+ or NADH was found. Phosphate ions enhanced the NAD+-dependent dehydrogenase activity and NADH-dependent reductase activity of the two enzymes, whereas the activities with NADP+ and NADPH were not affected. The ratios of the two activities of ketone reduction and 17 beta-hydroxysteroid oxidation of the two enzymes were almost constant during the purification steps after the two enzymes had been separated by DEAE-cellulose chromatography. By kinetic studies and electrophoresis and isoelectric focusing experiments it was confirmed that both of the two enzymes were responsile for the reduction aldehydes, ketones, and ketosteroids and for the oxidation of 17 beta-hydroxysteroids. These results indicate that 17 beta-hydroxysteroid dehydrogenases may play important roles in the metabolism of exogeneous aldehydes and ketones as well as steroids.
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PMID:Guinea pig liver aromatic aldehyde-ketone reductases identical with 17 beta-hydroxysteroid dehydrogenase isozymes. 4 Sep 69

1. A soluble enzyme which catalyses the NADPH-dependent reduction of 4-nitroacetophenone to 4-nitrophenylmethylcarbinol has been partially purified from human erythrocytes. 2.inter-individual or intra-individual differences in the enzymic activity were small except for very low activity observed in one subject with glucose 6-phosphate dehydrogenase deficiency resulting in decreased levels of NADPH. 3. The enzyme was inactivated above 50 degrees or on storage at 4 degrees for longer than 24 h. The pH optimum was between 7-0-8-0. 4. the enzyme has been differentiated from NADPH-methaemoglobin reductase, NADPH-cytochrome c reductase, glutathione reductase, alpha,beta-unsaturated ketone reductase and aromatic alpha-keto acid reductase activities, but similarities exist between this enzyme and a rabbit kidney cortex aromatic aldehyde/ketone reductase.
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PMID:The partial purification and properties of a human erythrocyte 4-nitroacetophenone reductase. 23 88

Some of the Beneckea harveyi dim aldehyde mutants, all of which emit light upon addition of exogenous long-chain aldehyde, also emit light when myristic acid is added. Analysis of these myristic acid-responsive mutants indicates that they are blocked before fatty acid formation, whereas another class of mutants, which respond only to aldehyde, appear to be defective in the enzyme(s) involved in the conversion of acid to aldehyde. Evidence is presented that this activity, designated myristic acid reductase, is coinduced with luciferase and is involved in the recycling of acid produced in the luciferase reaction, with specificity for the C14 compounds.
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PMID:Control of aldehyde synthesis in the luminous bacterium Beneckea harveyi. 31 59

Mild, acidic hydrolysis of 3-O-benzoyl-1,2,:5,6-di-O-isopropylidene-alpha-D-allofuranose gave a diol that was selectively benzoylated at O-6 in high yield by intermediate conversion to the stannylene derivative. The 3,6-dibenzoate was converted to the 5-O-tosyl derivative and thence to a mixture of iodides, which were reduced with tributylstannane to 3,6-di-O-benzoyl-1,2-O-isopropylidene-alpha-D-ribo-hexofuranose (6). Acetolysis gave an anomeric mixture of diacetates, which, when treated with N-acetylbis(trimethylsilyl)cytosine gave the protected nucleoside, which was deprotected to free "homocytidine", 1-(5-deoxy-beta-D-ribo-hexofuranosyl)cytosine (11), by alklaine methanolysis. This was N-acetylated and then treated with acetone to give a protected nucleoside, which was labelled by oxidation to the aldehyde, reduction with sodium borotritide, and deprotection. Acidic methanolysis of 6 gave a mixture of methyl 2,6- and 3,6-di-O-benzoylfuranosides, the hydroxyl groups of which were treated by the tetrachloromethane-triphenylphosphine reagent to give the 2-chloro-2-deoxy (21) and 3-chloro-3-deoxy derivatives. Reduction of 21 gave methyl 3,6-di-O-benzoyl-2,5-dideoxy-D-erythro-furanoside, further transformed in 1-(2,5-dideoxy-beta-D-erythro-hexofuranosyl)cytosine mixed with the alpha anomer. Phosphates and diphosphates of the nucleosides were prepared by extensions of known methods. The phosphate and the diphosphate of 11 act neither as substrates nor as inhibitors of a ribonucleotide-reductase from rat asicites tumor.
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PMID:[Synthese of 1-(5-deoxy-beta-D-ribo-hexofuranosyl)cytosine and 1-(2,5-dideoxy-beta-D-erythro-hexofuranosyl)cytosine, and their phosphates. Specificity of an mammalian (rat) ribonucleotide-reductase]. 51 57

1. The route of l-threonine degradation was studied in four strains of the genus Pseudomonas able to grow on the amino acid and selected because of their high l-threonine aldolase activity. Growth and manometric results were consistent with the cleavage of l-threonine to acetaldehyde+glycine and their metabolism via acetate and serine respectively. 2. l-Threonine aldolases in these bacteria exhibited pH optima in the range 8.0-8.7 and K(m) values for the substrate of 5-10mm. Extracts exhibited comparable allo-l-threonine aldolase activities, K(m) values for this substrate being 14.5-38.5mm depending on the bacterium. Both activities were essentially constitutive. Similar activity ratios in extracts, independent of growth conditions, suggested a single enzyme. The isolate Pseudomonas D2 (N.C.I.B. 11097) represents the best source of the enzyme known. 3. Extracts of all the l-threonine-grown pseudomonads also possessed a CoA-independent aldehyde dehydrogenase, the synthesis of which was induced, and a reversible alcohol dehydrogenase. The high acetaldehyde reductase activity of most extracts possibly resulted in the underestimation of acetaldehyde dehydrogenase. 4. l-Serine dehydratase formation was induced by growth on l-threonine or acetate+glycine. Constitutively synthesized l-serine hydroxymethyltransferase was detected in extracts of Pseudomonas strains D2 and F10. The enzyme could not be detected in strains A1 and N3, probably because of a highly active ;formaldehyde-utilizing' system. 5. Ion-exchange and molecular exclusion chromatography supported other evidence that l-threonine aldolase and allo-l-threonine aldolase activities were catalysed by the same enzyme but that l-serine hydroxymethyltransferase was distinct and different. These results contrast with the specificities of some analogous enzymes of mammalian origin.
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PMID:Bacterial catabolism of threonine. Threonine degradation initiated by L-threonine acetaldehyde-lyase (aldolase) in species of Pseudomonas. 91 18


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