Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Until recently the alcohol dehydrogenase of Drosophila melanogaster was thought to act only in the first step of primary alcohol oxidation, producing an aldehyde. Instead, acetic acid is the main product of a two-step process. A rapid procedure was developed for the isolation and purification of two allozymes. The thermostability of the purified enzymes was found to be very different, t 1/2 at 35 degrees C, being 45 min and 130 min for ADH-F and ADH-71k respectively. The kinetic parameters of ethanol oxidation by the two purified allozymes were determined within physiological substrate and coenzyme ranges. The use of artificial electron acceptors has a notable influence on the ethanol oxidation: the apparent Michaelis constants increase; the oxidation rate with ADH-71k increases, whereas it decreases with ADH-F. Purified ADH is shown to be able to catalyze the oxidation of acetaldehyde solely in the presence of NAD+, and PMS and MTT as artificial electron acceptors. From the kinetic data the relative in vivo oxidation rates of ethanol by both ADH allozymes were calculated. ADH-F turned out to be somewhat less effective (30%-40%) than ADH-71k. The physiological consequences of these differences are discussed.
Mol Gen Genet 1985
PMID:Dual function of the alcohol dehydrogenase of Drosophila melanogaster: ethanol and acetaldehyde oxidation by two allozymes ADH-71k and ADH-F. 315 99

One of the mutagenic byproducts associated with chlorinated humic waters and kraft pulp bleaching effluents was recently identified as 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone. This compound and several related chlorofuranones and precursors were synthesized and evaluated for direct-acting mutagenicity in Salmonella typhimurium tester strain TA100. Mutagenicity was greatest for 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone, its 5-methoxy derivative, and the precursor in their synthesis, 3-(dichloromethyl)-2,4,4-trichloro-2-butenoic acid. Several of the compounds were tested in the presence of added rat liver homogenate S9 fraction, and in all cases mutagenicity was substantially reduced. An important structural feature which may govern the mutagenic response in these instances appears to be the cis arrangement of CHCl2 and Cl substituents on a carbon-carbon double bond. These compounds may also be transformed in vitro to the same acyclic chlorine substituted alpha, beta-unsaturated aldehyde derivative, which is proposed to be the agent responsible for the observed mutagenicity.
Environ Mol Mutagen 1988
PMID:Mutagenic potency of chlorofuranones and related compounds in Salmonella. 327 97

Authors critically review current data about biochemical-physiological factors mediating genetic predisposition to alcoholism. Results of genetic investigation of the ethanol and acetaldehyde metabolism and the facts about enzyme polymorphism of systems of the ethanol biotransformation and genetic polymorphism of particular enzymes are summarized. Data about possible determinants of nervous system sensitivity to ethanol action are considered. The investigation of genetic basis of phenomena imminent to alcoholism by use of laboratory animals is discussed.
Mol Gen Mikrobiol Virusol 1987 Apr
PMID:[Alcoholism and heredity: biological basis of the predisposition to alcoholism]. 329 66

The ability of diethyl ether to serve as a substrate for microsomal and purified cytochrome P-450 (P-450) and as an inducer for rat hepatic microsomal monooxygenase activities was examined. Microsomal oxidation of ether to acetaldehyde, as monitored by high pressure liquid chromatography, was elevated 3- to 5-fold by treatment of rats with acetone or ethanol, 1.5- to 2-fold by treatment with ether, and only slightly by phenobarbital treatment. Ether also induced N-nitrosodimethylamine demethylase by up to 2-fold and 7-pentoxyresorufin dealkylation by up to 10-fold. These trends agreed with immunoblot experiments in which ether was a weak inducer of the P-450 isozyme IIE1 (encoded by the rat gene P450IIE1), but a stronger inducer of IIB1. A monoclonal antibody against IIE1 inhibited the deethylation by 78% in microsomes from acetone-treated rats and by 45% in controls. N-Nitrosodimethylamine, as well as common inhibitors of IIE1 such as hexane, benzene, pyrazole, and phenylethylamine, strongly inhibited ether deethylation. Using microsomes from acetone-induced rats, the apparent Km for deethylation was 13.4 +/- 2.4 microM and the Vmax was 8.2 +/- 0.2 (nmol of acetaldehyde/min/nmol of P-450). The Km for the controls was 71.3 +/- 9.5 microM. The rates of deethylation at 1 mM ether by purified, reconstituted IIE1 and IIB1 were 4.2 and 0.42 (nmol of acetaldehyde/min/nmol of P-450), respectively. Cytochrome b5 stimulated the rate due to IIE1 apparently by a decrease in the Km. These findings, along with previous work showing marked inhibition by ether of IIE1-dependent reactions, strongly support a major role for this isozyme in ether metabolism.
Mol Pharmacol 1988 Feb
PMID:Diethyl ether as a substrate for acetone/ethanol-inducible cytochrome P-450 and as an inducer for cytochrome(s) P-450. 334 79

Mutants of Escherichia coli resistant to chloroethanol or to chloroacetaldehyde were selected. Such mutants were found to lack the fermentative coenzyme A (CoA) linked acetaldehyde dehydrogenase activity. Most also lacked the associated fermentative enzyme alcohol dehydrogenase. Both types of mutants, those lacking acetaldehyde dehydrogenase alone or lacking both enzymes, mapped close to the regulatory adhC gene at 27 min on the E. coli genetic map. The previously described acd mutants which lack acetaldehyde dehydrogenase and which map at 63 min were shown to be pleiotropic, affecting respiration and growth on a variety of substrates. It therefore seems likely that the structural genes for both the acetaldehyde and alcohol dehydrogenases lie in the adhCE operon. This interpretation was confirmed by the isolation of temperature sensitive chloracetaldehyde-resistant mutants, some of which produced thermolabile acetaldehyde dehydrogenase and alcohol dehydrogenase and were also found to map at the adh locus. Reversion analysis indicated that mutants lacking one or both enzymes carried single mutations. The gene order in the adh region was determined by three point crosses to be trp-zch::Tn10-adh-galU-bglY-tyrT-chlC.
Mol Gen Genet 1986 Dec
PMID:The use of suicide substrates to select mutants of Escherichia coli lacking enzymes of alcohol fermentation. 355 Mar 85

The genes of Photobacterium leiognathi luminescence system were cloned in plasmid pUC18. Escherichia coli cells harboring a recombinant plasmid pPHL1 are luminescent. pPHL1 contains luciferase genes and genes responsible for aldehyde biosynthesis. The luminescence of Escherichia coli is subject to autoinductor regulation similar to the one existing in luminescent bacteria. The 2.7 kb fragment of Photobacterium leiognathi DNA containing the genes for alpha- and beta-luciferase subunits were cloned in pUC19.
Mol Gen Mikrobiol Virusol 1987 Aug
PMID:[Cloning and expression of genes of the luminescence system in Photobacterium leiognathi]. 368 27

The in vitro metabolism of phenelzine (2-phenylethylhydrazine) by phenobarbital-pretreated rat liver microsomes yields ethylbenzene, 2-phenylethanol, 2-phenylacetaldehyde, benzaldehyde, benzylalcohol, and toluene as metabolites. Isotopic studies demonstrate that the oxygen atom of 2-phenylethanol derives from molecular oxygen and that this alcohol is not produced by reduction of 2-phenylacetaldehyde. The rates of destruction of cytochrome P-450, accumulation of spin-trapped 2-phenylethyl radicals, and formation of ethylbenzene and 2-phenylethanol are the same for [1,1-2H]-2-phenylethylhydrazine as for the undeuterated substrate. Small primary isotope effects are observed, however, for the formation of 2-phenylacetaldehyde (kH/kD greater than 1) and benzaldehyde (kH/kD less than 1). Synthetic 2-phenylethylhydroperoxide is converted by liver microsomes to the same alcohol and aldehyde metabolites. The results indicate that the metabolism of phenelzine by rat liver microsomes proceeds primarily via the 2-phenylethyl radical.
Mol Pharmacol 1987 Feb
PMID:Free radical pathways in the in vitro hepatic metabolism of phenelzine. 380 96

Various preparatory procedures were tested to preserve the ultrastructure of the sarcoplasmic reticulum (SR) by the best possible method within frog sino-atrial muscle fibres. These procedures were: conventional aldehyde fixation with or without tannic acid, cryofracture, metallic impregnation and quick-freezing followed by freeze-substitution. Our results illustrated that, when optimally preserved, the SR architecture and ultrastructure of frog sino-atrial fibres were not fundamentally different from those described in many other vertebrate muscle fibres, particularly cardiac fibres. The three-dimensional arrangement of the SR and the structure of its main compartments were situated in a precise fashion: the peripheral SR, located close to the plasma membrane, was made of a tight network of tubules and showed typical couplings; the juxtafibrillar SR was made of a loose network of tubules, small cisternae and some tubules near Z-lines; the intermediary SR, associated with the mitochondria, was made of tubules and fenestrated cisternae. Contacts between SR and mitochondrial membranes were also studied; cryofractures revealed no special intramembrane particles at this level. Collapsed portions of the SR were found after quick-freezing. Because of its relative importance and its three-dimensional arrangement, the SR of frog sino-atrial fibres may have comparable functional significance to the SR of other cardiac muscle fibres.
J Mol Cell Cardiol 1985 Jan
PMID:Ultrastructure and architecture of the sarcoplasmic reticulum in frog sino-atrial fibres: a comparative study with various preparatory procedures. 388 16

The naturally occurring serine protease inhibitor, chymostatin, forms a hemiacetal adduct with the catalytic Ser195 residue of Streptomyces griseus protease A. Restrained parameter least-squares refinement of this complex to 1.8 A resolution has produced an R index of 0 X 123 for the 11,755 observed reflections. The refined distance of the carbonyl carbon atom of the aldehyde to O gamma of Ser195 is 1 X 62 A. Both the R and S configurations of the hemiacetal occur in equal populations, with the end result resembling the expected configuration for a covalent tetrahedral product intermediate of a true substrate. This study strengthens the concept that serine proteases stabilize a covalent, tetrahedrally co-ordinated species and elaborates those features of the enzyme responsible for this effect. We propose that a major driving force for the hydrolysis of peptide bonds by serine proteases is the non-planar distortion of the scissile bond by the enzyme, which thereby lowers the activation energy barrier to hydrolysis by eliminating the resonance stabilization energy of the peptide bond.
J Mol Biol 1985 May 05
PMID:The 1.8 A structure of the complex between chymostatin and Streptomyces griseus protease A. A model for serine protease catalytic tetrahedral intermediates. 389 18

Gunn rats have a marked deficiency in hepatic UDP-glucuronosyl transferase activity which results in hyperthyroxinemia and hyperbilirubinemia. Their thyroids show a brownish-black discoloration associated ultrastructurally with intracellular dense granules and intraluminal dense masses. In order to determine whether colloid composition and colloid proteolysis are altered in the thyroid of the Gunn rat compared with the Wistar rat, we studied the in situ resistance of thyroid proteins to in vitro proteolysis, the pattern of in vivo (125I) labeled thyroid iodoproteins and the proteolysis of isolated iodoprotein fractions in both strains of rats. For the cytochemical study, thin sections of aldehyde-fixed and plastic-embedded thyroid tissue were treated with 0.3 or 1% pronase in aqueous solution. With the low concentration of pronase, the secretory granules in C-cells and the apical vesicles in follicular cells were extensively digested in both strains of rats, whereas the colloid in the follicular lumen and the colloid droplets were only partially digested. With the high concentration of pronase, the colloid in the lumen and the colloid droplets were more markedly digested in both strains. In the presence of both concentrations of pronase, the dense granules and intraluminal dense masses were unchanged in the Gunn rats. The (125I) iodoprotein pattern was investigated 24 h after a single injection of (125I) iodide and by labeling at the isotopic equilibrium. It was found that the (125I) thyroglobulin fraction was reduced, whereas the (125I) 3-8 S fraction was increased in Gunn rats compared to Wistar rats. Pronase hydrolysis of the soluble (125I) iodine fraction showed similar pronase-resistant fractions in both strains with the single labeling procedure. At the isotopic equilibrium, the pronase resistant fraction was significantly increased in Gunn rats (Gunn 24.0 +/- 5.3%; Wistar: 13.7 +/- 3.1% of the soluble 125I) and a linear correlation was observed between the (125I) 3-8 S fraction of the soluble extract and the pronase-resistant fraction. These data suggest that iodocompounds of small molecular size and low turnover accumulate in the thyroid of the Gunn rat due to their strong resistance to in vivo hydrolysis. A local accumulation of 3-8 S iodocompounds may occur within the intracellular dense granules and intraluminal dense masses in the thyroid of Gunn rat.
Virchows Arch B Cell Pathol Incl Mol Pathol 1983
PMID:Abnormal iodoprotein distribution and resistance to proteolysis in Gunn rat black thyroid. An ultrastructural and biochemical study. 614 65


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