Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.1.1.1 (alcohol dehydrogenase)
 9,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An NADPH-dependent aldehyde reductase was purified from rat brain microsomes to electrophoretic homogeneity. The purified enzyme had a molecular weight of 75,000 and reduced long chain fatty aldehydes such as octanal and hexadecanal with higher affinity (Km values of 0.21 mM and 0.03 mM, respectively) than for various artificial carbonyl compounds such as p-nitrobenzaldehyde and p-nitroacetophenone (Km values of 0.31 mM and 1.4 mM, respectively). The purified microsomal aldehyde reductase also showed NADPH-cytochrome c reductase activity, and it could not be distinguished from NADPH-cytochrome c reductase in molecular weight (75,000), chromatographic behavior, electrophoretic mobility, or immunological properties. The solubilized microsomal fraction treated with steapsin lost the reductase activity for hexadecanal but not that for cytochrome c. These results suggest that the aldehyde reductase in brain microsomes is identical to NADPH-cytochrome c reductase and that a hydrophobic portion of the NADPH-cytochrome c reductase is required for the reduction of hexadecanal.
 ...
PMID:Characterization of microsomal NADPH-dependent aldehyde reductase from rat brain. 308 64

Aldose reductase [aldehyde reductase 2; alditol:NAD(P)+ 1-oxidoreductase, EC 1.1.1.21] catalyzes conversion of glucose to sorbitol. Although its activity is implicated in the progression of ocular and neurological complications of diabetes, the normal function of the enzyme in most cells is unknown. Both aldose reductase activity and substantial levels of sorbitol were previously reported in renal inner medullary cells. In this tissue, the extracellular NaCl concentration normally is high and varies considerably depending on the urine concentration. We report here on a line of renal medullary cells in which medium that is high in NaCl greatly increases both aldose reductase activity and intracellular sorbitol. In these tissue culture cells (and presumably also in the renal inner medulla), the intracellular sorbitol helps balance the osmotic pressure of elevated extracellular NaCl and thus prevents cellular dehydration.
 ...
PMID:Induction of aldose reductase and sorbitol in renal inner medullary cells by elevated extracellular NaCl. 310 2

Aldose reductase (EC 1.1.1.21) has been implicated in a variety of diabetic complications. Here we present the first primary sequence data for the rat lens enzyme, obtained by amino acid and cDNA analysis. We have found structural similarities with another NADPH-dependent oxidoreductase: human liver aldehyde reductase (EC 1.1.1.2). The identity between these two enzymes is 50%. Both enzymes share approx. 40-50% homology with p-crystallin, a major lens protein present only in the frog, Rana pipiens. We propose that aldose reductase, aldehyde reductase and p-crystallin are members of a superfamily of related proteins.
 ...
PMID:Aldose reductase and p-crystallin belong to the same protein superfamily as aldehyde reductase. 311 86

Aldehyde reductase (alcohol:NADP+ oxidoreductase, EC 1.1.1.2), aldose reductase (alditol:NAD(P)+ 1-oxidoreductase, EC 1.1.1.21) and carbonyl reductase (secondary-alcohol:NADP+ oxidoreductase, EC 1.1.1.184) constitute the enzyme family of the aldo-keto reductases, a classification based on similar physicochemical properties and substrate specificities. The present study was undertaken in order to obtain information about the structural relationships between the three enzymes. Treatment of human aldehyde and carbonyl reductase with phenylglyoxal and 2,3-butanedione caused a complete and irreversible loss of enzyme activity, the rate of loss being proportional to the concentration of the dicarbonyl reagents. The inactivation of aldehyde reductase followed pseudo-first-order kinetics, whereas carbonyl reductase showed a more complex behavior, consistent with protein modification cooperativity. NADP+ partially prevented the loss of activity of both enzymes, and an even better protection of aldehyde reductase was afforded by the combination of coenzyme and substrate. Aldose reductase was partially inactivated by phenylglyoxal, but insensitive to 2,3-butanedione. The degree of inactivation with respect to the phenylglyoxal concentration showed saturation behavior. NADP+ partially protected the enzyme at low phenylglyoxal concentrations (0.5 mM), but showed no effect at high concentrations (5 mM). These findings suggest the presence of an essential arginine residue in the substrate-binding domain of aldehyde reductase and the coenzyme-binding site of carbonyl reductase. The effect of phenylglyoxal on aldose reductase may be explained by the modification of a reactive thiol or lysine rather than an arginine residue.
 ...
PMID:Inactivation of carbonyl reductase from human brain by phenylglyoxal and 2,3-butanedione: a comparison with aldehyde reductase and aldose reductase. 311 57

Aldose reductase from human placenta was purified to homogeneity by a rapid (2 day) and efficient purification scheme involving Red Sepharose affinity chromatography, chromatofocusing and high performance liquid chromatography on a size-exclusion column. Addition of NADP+ at all steps in the purification of aldose reductase and during storage of the enzyme at -20 degrees stabilized both the enzyme active site and the major site for binding of aldose reductase inhibitors such as sorbinil and tolrestat. Aldose reductase is a monomer with a molecular mass of 38 kD by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, apparent pI 5.9. Placenta aldose reductase exhibited no cross-reactivity with aldehyde reductase from human liver in an ELISA assay. Aldose reductase showed broad specificity for aldehydes, was specific for NADPH, and was activated by sulfate.
 ...
PMID:Purification of aldose reductase from human placenta and stabilization of the inhibitor binding site. 312 93

The participation of microsomal aldehyde reductase in long-chain fatty alcohol synthesis in the rat brain was examined. A reaction mixture of [1-14C]hexadecanoic acid with brain microsomes and NADPH formed two radioactive products having the same mobilities as pure hexadecanal (RF 0.61) and hexadecanol (RF 0.22), respectively, on TLC plates. The product of the RF 0.61 spot was further identified as hexadecanal using gas-liquid chromatography after methylation and TLC of its reduced product with LiAlH4 and semicarbazide. The ratio of hexadecanal to hexadecanol varied from 0.4 to 1.2 under the present experimental conditions. When solubilized rat brain microsomes were applied to a Sepharose 4B column coupled with the rabbit antibody raised against rat liver microsomal NADPH-cytochrome-c reductase, which reacts with aldehyde reductase from rat brain, the eluted fraction ceased to form [14C]hexadecanol but continued to form [14C]hexadecanal from [14C]hexadecanoic acid. These results strongly indicate that hexadecanal is the intermediate in the synthesis of hexadecanol from hexadecanoic acid in rat brain microsomes with the participation of microsomal aldehyde reductase.
 ...
PMID:Participation of microsomal aldehyde reductase in long-chain fatty alcohol synthesis in the rat brain. 314 13

A major and a minor form of dihydrodiol dehydrogenase were co-purified with 17 beta-hydroxysteroid dehydrogenase and aldehyde reductase, respectively, to apparent homogeneity from liver cytosol of male ddY mice. The activities of dihydrodiol dehydrogenase and testosterone dehydrogenase or aldehyde reductase of the two enzyme forms comigrated electrophoretically. The major form of the enzyme oxidized 17 beta-hydroxysteroids and nonsteroidal alicyclic alcohols and reduced 17-ketosteroids and various synthetic carbonyl compounds, showing higher affinity for steroids than for xenobiotics. The activity of this enzyme form toward benzene dihydrodiol and testosterone exhibited identical thermostability and susceptibility to inhibition by quercitrin, SH-reagents, nonsteroidal estrogens and anti-inflammatory agents. On the other hand, the minor form of the enzyme, which oxidized benzene dihydrodiol but not 17 beta-hydroxysteroids, also reduced various aldehydes well and was specifically inhibited by barbiturates and sorbinil. These results indicate that the major form of dihydrodiol dehydrogenase is identical to 17 beta-hydroxysteroid dehydrogenase and the minor enzyme form to aldehyde reductase.
 ...
PMID:Mouse liver dihydrodiol dehydrogenases. Identity of the predominant and a minor form with 17 beta-hydroxysteroid dehydrogenase and aldehyde reductase. 327 26

Two major forms of aldehyde reductase (AHR) activity were resolved following zone electrophoresis of mouse lung homogenates and distinguished by their differential substrate and inhibitor specificities: alcohol dehydrogenase (ADH) C2 and carbonyl reductase (CBR). CBR was purified to homogeneity by DEAE-cellulose chromatography, affinity chromatography using Blue-sepharose, followed by gel filtration on Sephacryl S-200. The enzyme exhibited a native MW of 122,000, comprising 4 identical subunits. Kinetic and inhibition characteristics resembled those reported by Nakayama and coworkers (1982) for guinea pig lung CBR. Mouse lung CBR exhibited optimal activity at pH 5.0; a preference for NADPH as coenzyme, although reactive with NADH at an order of magnitude higher concentration; poor activity as an ADH, but was strongly inhibited by 4-methyl pyrazole; and was inhibited by quercitin, dithiothreitol and p-OH-mercuribenzoate, but was insensitive to valproate or sorbinil. These properties, coupled with the activity of CBR with a range of aliphatic and aromatic aldehydes, ketones and quinones, distinguish it from other AHRs. The unique localization in lung tissue suggests a possible role for CBR in the detoxification of xenobiotics and of toxic aldehydes derived from lipid peroxidation processes.
 ...
PMID:Lung carbonyl reductase in the mouse: biochemical and catalytic properties. 330 39

The inhibition of the major form of ox kidney aldehyde reductase (AR 1) by sodium barbitone revealed linear mixed kinetics. This behaviour is distinct from the non-linear intercept effect we reported for valproate [Daly and Mantle (1982) Biochem. J. 205, 381]. 4-Carboxybenzaldehyde exhibits partial uncompetitive substrate inhibition. These results are discussed in terms of a model that involves nucleotide-induced isomerization and an additional flux (with some substrates and inhibitors) through an enzyme.nucleotide.substrate/inhibitor ternary complex.
 ...
PMID:Kinetic studies on the major form of aldehyde reductase in ox kidney: a general kinetic mechanism to explain substrate-dependent mechanisms and the inhibition by anticonvulsants. 350 11

Four major and four minor dihydrodiol dehydrogenases, with similar apparent molecular weights of 28,000 to 34,000 but with different charges, were purified from male guinea pig liver cytosol. One of the minor enzymes catalyzed only the oxidation of benzene dihydrodiol with a high Km value of 5.0 mM and was identified immunologically with aldehyde reductase. The other enzymes oxidized xenobiotic alicyclic alcohols and 17 beta-hydroxysteroids as well as benzene dihydrodiol. These enzymes exhibited higher affinity for 17 beta-hydroxysteroids than for alicyclic alcohols and benzene dihydrodiol, and immunologically cross-reacted with testosterone 17 beta-dehydrogenase purified from the same source. Four major enzymes and one minor with Km values for benzene dihydrodiol of about 0.2 mM, possessed specificity for 5 beta-androstane--17 beta-hydroxysteroids and dual cofactor requirement, whereas the other two minor enzymes with high Km values of over 5 mM showed apparent NADP and 5 alpha-androstane specificity. The dihydrodiol dehydrogenase activity was localized in the cytosol of liver. The results indicate that the hepatic oxidation of dihydrodiols in the guinea pig is mediated by cytosolic testosterone 17 beta-dehydrogenase isozymes and aldehyde reductase. Testosterone 17 beta-dehydrogenase immunologically identical to the liver enzymes was detected only in kidney, whereas aldehyde reductase was detected in all tissues of the guinea pig.
 ...
PMID:Dihydrodiol dehydrogenases in guinea pig liver. 353 6


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