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

Menadione bisulfite is a hepatotoxicant that damages periportal regions of the lobule in perfused liver in an oxygen-dependent manner. The effect of ethanol on menadione bisulfite toxicity was examined in perfused rat liver. Addition of menadione bisulfite (3 mM) alone to the perfusate increased oxygen uptake by 20-30 mumols/g/hr. Lactate dehydrogenase was released into the effluent after 60 min of perfusion and reached values around 100 units/g/hr. Under these conditions, trypan blue was taken up exclusively in periportal regions of the liver lobule; 44% of periportal cells were stained. In the presence of ethanol, maximal increases in oxygen uptake due to menadione bisulfite were much larger (about 90 mumols/g/hr), and lactate dehydrogenase release occurred earlier and reached higher maximal values (330 units/g/hr). Trypan blue staining was also more extensive; 90% of periportal cells were stained. The effect of ethanol on menadione bisulfite-induced oxygen uptake required metabolism via alcohol dehydrogenase (ADH), because ethanol increased oxygen uptake due to menadione bisulfite from 44 to 81 mumols/g/hr in deermice with ADH but had no effect in deermice lacking ADH. Other agents that increase NADH (xylitol and 2-ethyl-1-hexanol) also potentiated the stimulation of oxygen uptake due to menadione bisulfite, suggesting that ethanol was working by increasing the NADH redox state. Cyanide abolished the increase in oxygen uptake due to menadione bisulfite, both in the absence and in the presence of ethanol, supporting the hypothesis that the effect of ethanol on menadione bisulfite-mediated oxygen uptake involves the mitochondrial respiratory chain. Further, the stimulation of oxygen uptake by menadione bisulfite in isolated mitochondria was enhanced when matrix NADH was increased by addition of beta-hydroxybutyrate. These data indicate that ethanol potentiates oxygen uptake and toxicity due to menadione bisulfite most likely by generation of NADH for redox cycling of this model quinone.
Mol Pharmacol 1990 Dec
PMID:Ethanol potentiates oxygen uptake and toxicity due to menadione bisulfite in perfused rat liver. 225 Jun 68

The mechanisms by which ethanol (EtOH, 1.5 g/kg) inhibits testicular testosterone synthesis were studied in nonstimulated and human chorionic gonadotropin (hCG, 50 IU/kg)-treated male rats. To dissociate the effects caused by ethanol metabolism, the alcohol dehydrogenase inhibitor 4-methylpyrazole (4MP, 10 mg/kg) was given to half of the rats 30 min before EtOH. The 4MP had little or no effect in the nonstimulated rats on the EtOH-induced decreases in the concentrations of serum testosterone and of the intratesticular steroids of the testosterone biosynthetic pathway measured, but reduced the EtOH-induced elevation in the intratesticular pregnenolone-to-progesterone ratio. In contrast, 4MP pretreatment markedly reversed the EtOH-induced decrease in serum and intratesticular testosterone and increase in intratesticular pregnenolone concentrations in the hCG-stimulated rats. Simultaneously, the EtOH-induced elevations in the intratesticular pregnenolone/progesterone and androstenedione/testosterone ratios were abolished. In the EtOH-treated rats whose EtOH metabolism was blocked by 4MP pretreatment, the intratesticular testosterone concentrations were negatively correlated with the elevated serum corticosterone levels. It is concluded that: (1) EtOH metabolism is involved in the inhibition of testicular steroidogenesis in vivo. This effect is pronounced during gonadotropin-stimulated conditions. Thus, previously reported "discrepancies" between the in vivo and in vitro results are clarified; (2) corticosterone seems also to be involved in the EtOH-induced inhibition of steroidogenesis. This effect is also pronounced during gonadotropin-stimulated conditions; and (3) without external gonadotropin stimulation other inhibitory mechanisms, such as decreased stimulation by luteinizing hormone, are prevalent.
J Steroid Biochem Mol Biol 1990 Oct
PMID:Role of ethanol metabolism in the inhibition of testosterone biosynthesis in rats in vivo: importance of gonadotropin stimulation. 226 60

The roles of the TATA element and sequences near the mRNA initiation site in specifying the location of initiation sites in Saccharomyces cerevisiae were examined, using the Schizosaccharomyces pombe ADH gene. The importance of spacing was demonstrated by analysis of a series of deletions that removed from 8-50 bp between the TATA element and ATG translation initiation site of this gene. Primer extension mapping showed that increasing deletion length is associated with a progressive shift downstream in the location of the initiation sites. The distance of a given site from the promoter affected the relative ability of the site to be utilized for initiation. For this gene, a permissive region for transcription initiation exists between 55 and 125 bases downstream of the TATA element, and a zone of 75-115 bases allows maximal usage of an initiation site. The presence of a TATA sequence was shown to be necessary in S. cerevisiae for maintaining the location of this "window" of initiation. The TATA sequence is essential for function of the gene in S. pombe. This gene, as well as the majority of the 63 S. cerevisiae genes surveyed, uses initiation sites which fit a PyAA/T(Pu) consensus. Cis-acting mutations were recovered which restored ADH activity to a deletion allele that initiates its mRNAs downstream of the ATG. DNA sequence and transcript analysis with these mutants confirmed the requirement of proper spacing and conformity of initiation sites to the PyAA/T(Pu) consensus for efficient transcript initiation.
Mol Gen Genet 1990 Sep
PMID:DNA sequence elements required for transcription initiation of the Schizosaccharomyces pombe ADH gene in Saccharomyces cerevisiae. 227 81

An alcohol dehydrogenase was shown to be induced in Aspergillus nidulans by periods of anaerobic stress. This alcohol dehydrogenase was shown to correspond to the previously described cryptic enzyme, alcohol dehydrogenase III (McKnight et al. 1985), by analysis of a mutation in the structural gene of alcohol dehydrogenase III, alcC, created by gene disruption. Survival tests on agar plates showed that this enzyme is required for long-term survival under anaerobic conditions. Northern blot analysis and gene fusion studies showed that the expression of the alcC gene is regulated at both the transcriptional and translational levels. Thus there are mechanisms in this filamentous fungus allowing survival under anaerobic stress that are similar to those described in higher plants.
Mol Gen Genet 1990 Jul
PMID:Alcohol dehydrogenase III in Aspergillus nidulans is anaerobically induced and post-transcriptionally regulated. 227 33

Six independent mutant lines of Nicotiana plumbaginifolia resistant to ethanol, designated E3, E8, E101, E112, E144 and E251, were isolated as germinating seedlings on selective medium. In all cases, resistance to ethanol was conferred by a single recessive nuclear mutation at the same locus. Mutant seeds and pollen lacked detectable ADH activity, with the exception of E251 where a residual activity was detected. An antiserum directed against Arabidopsis thaliana ADH detected an ADH-related polypeptide of 44 kDa present in wild-type seeds and, to a lesser extent, in the seeds of the leaky mutant E251. No ADH-related polypeptide could be detected in seeds of the other mutants. However, all of them had a nearly normal level of ADH mRNA except one which did not synthesize any mRNA. These results suggest that these ethanol-resistant mutants are impaired in one of the structural genes coding for alcohol dehydrogenase. The corresponding locus has been designated Adh1.
Mol Gen Genet 1990 Jul
PMID:Ethanol-resistant mutants of Nicotiana plumbaginifolia are deficient in the expression of pollen and seed alcohol dehydrogenase activity. 227 39

Data presented in this paper deal with a further molecular characterization of 2 out of 32 EMS-induced Arabidopsis ADH null mutants that we isolated previously. In order to localize and characterize each mutation at the molecular level, we have cloned and completely sequenced the R002 and R006 null mutant alleles. For mutant R002, which does not contain any detectable levels of ADH protein and mRNA, we have found that the mutation is due to a single C to T base pair substitution in the reading frame; this leads to the incorporation of a TAG stop codon (amber nonsense mutation). For mutant R006, which contains normal levels of inactive protein and mRNA levels, we found a G to A base pair transition. This gives rise to a Cys to Tyr amino acid substitution in the active site of the ADH enzyme.
Mol Gen Genet 1990 Nov
PMID:Sequence analysis of two null-mutant alleles of the single Arabidopsis Adh locus. 227 48

Phylogenetic relationships and rates of nucleotide substitution were studied for alcohol dehydrogenase (ADH) genes by using DNA sequences from mammals and plants. Mammalian ADH sequences include the three class I genes and a class II gene from humans and one gene each from baboon, rat, and mouse. Plant sequences include two ADH genes each from maize and rice, three genes from barley, and one gene each from wheat and two dicots, Arabidopsis and pea. Phylogenetic trees show that relationships among ADH genes are generally consistent with taxonomic relationships: mammalian and plant ADH genes are classified into two distinct groups; primate class I genes are clustered; and two dicot sequences are clustered separately from monocot sequences. Accelerated evolution has been detected among the duplicated ADH genes in plants, in which synonymous substitutions occurred more often within the coenzyme-binding domain than within the catalytic domains.
Mol Biol Evol 1990 Mar
PMID:Molecular evolution of the zinc-containing long-chain alcohol dehydrogenase genes. 231 42

Free radical metabolism of ethanol has been suggested as a factor in its hepatotoxicity. Although evidence of lipid radical formation due to ethanol treatment in vivo has been reported, free radicals from ethanol itself have not been detected in living animals. However, by applying the EPR spectroscopy technique of spin trapping to the study of ethanol-treated alcohol dehydrogenase-deficient deermice (Peromyscus maniculatus), we have detected the alpha-(4-pyridyl-1-oxide)-N-t-butylnitrone (POBN)/alpha-hydroxyethyl radical adduct in bile from animals administered [1-13C]ethanol and the spin trap POBN. Hyperfine coupling constants were aN = 15.48, a beta H = 2.02, and a beta 13C = 4.61 G. In addition, an ethanol-dependent but 13C-invariant radical adduct, presumably lipid derived, was detected. Hyperfine coupling constants were aN = 15.38 and a beta H = 2.5 G. This report demonstrates, for the first time, the in vivo formation of the alpha-hydroxyethyl free radical metabolite of ethanol.
Mol Pharmacol 1990 Jul
PMID:In vivo formation of a free radical metabolite of ethanol. 237 Aug 54

AdhnLA248 is an X-ray-induced mutation of the alcohol dehydrogenase gene of Drosophila melanogaster that lacks detectable ADH protein but is transcribed. The transcript of this mutant allele is longer than that of the wild type. This is because the mutation is a duplication of parts of the second and third exons of Adh and of the intron that normally separates them. The primary transcript of the mutant allele is processed by the removal of both of the identical copies of intron 3. This mutation presumably originated, in the haploid sperm, as two staggered single-stranded breaks that gave rise to the duplication as a consequence of replication after fertilization.
J Mol Biol 1985 Dec 20
PMID:Mutation of the Adh gene of Drosophila melanogaster containing an internal tandem duplication. 241 73

Linkage was established between a number of genes that map on chromosome 3 by studying the distribution patterns of DNA polymorphisms and protein electrophoretic mobility polymorphisms in recombinant inbred (RI) strains of mice. This analysis resulted in the following suggested gene order between the newly assigned genes and previously mapped genes: gamma-fibrinogen (Fgg), Xmmv-22 of mink cell focus-inducing (MCF) virus, U1b small nuclear RNA gene cluster (Rnu-1b), amylase (Amy-1,2), cadmium resistance (cdm), alcohol dehydrogenase-3 (Adh-3), alcohol dehydrogenase-1 (Adh-1). In situ hybridization to chromosome spreads confirmed the assignment of the Ulb small nuclear RNA (snRNA) gene cluster and the gamma-fibrinogen gene to the center of chromosome 3.
Somat Cell Mol Genet 1988 Mar
PMID:Mapping and gene order of U1 small nuclear RNA, endogenous viral env sequence, amylase, and alcohol dehydrogenase-3 on mouse chromosome 3. 245 Apr 6


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