Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of ethanol on membrane enzymes (Na+, K+ and Mg2+ ATPases, 5'-nucleotidase, adenylate cyclase) alcohol dehydrogenase, aldehyde dehydrogenase and superoxide dismutase were studied in nerve cells (established cell lines, primary cultures of chick and rat brain) cultured in the presence of 100 mM ethanol, and in total rat brain, following various ethanol treatments of the rats (20% ethanol as the sole liquid source, intraperitoneal injection). The results show a difference between neuronal and glial cells. Most of the observed changes in enzymatic activities returned rapidly to control values when ethanol was withdrawn from the culture medium or from the diet. Alcohol dehydrogenase was more stimulated by ethanol than aldehyde dehydrogenase; therefore acetaldehyde may be accumulated. The inhibition of superoxide dismutase activity may allow an accumulation of cytotoxic O2- radicals in nervous tissue and may explain the polymorphism of lesions brought about by alcohol intoxication.
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PMID:Ethanol and neuronal metabolism. 626 95

We investigated the inhibitory effects of intracellular cyclic adenosine monophosphate (cAMP) levels in regulating class 3 aldehyde dehydrogenase (aldh3) gene expression using cultures of primary rat hepatocytes and transient transfection experiments with HepG2 cells. In addition to regulation by an Ah receptor-dependent mechanism, expression of many members of the Ah gene battery have been shown to be negatively regulated. As was seen for the cytochrome P450 (cyp1A1) gene, aldh3 is transcriptionally inducible by polycyclic aromatic hydrocarbons (PAH), and this induction involving function of the arylhydrocarbon (Ah) receptor is inhibited by the protein kinase C (PKC) inhibitors, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine di-HCl (H7) and staurosporine. However, PAH induction of ALDH-3 activity, protein, and mRNA was potentiated 2-4-fold by addition of the protein kinase A (PKA) inhibitors, N-(2-(methylamino)ethyl)-5-isoquinolinesulfonamide di-HCl (H8) and N-(2-guanidinoethyl)-5-isoquinolinesulfonamide HCl (HA1004). These PKA inhibitors had no effect on the PAH induction of the cyp1A1. Protein kinase A activity of cultured hepatocytes was specifically inhibited by H8 and HA1004 in a concentration-dependent manner, but not by H7, and there was an inverse correlation observed between potentiation of PAH-induced aldh3 gene expression and inhibition of specific PKA activity by the PKA inhibitors. The cAMP analog dibutyryl cAMP, the adenylate cyclase activator forskolin, and the protein phosphatase 1 and 2A inhibitor okadaic acid all dramatically inhibited both PAH induction and H8 potentiation of PAH induction of aldh3 expression but had no effect on induction of cyp1A1 expression in cultured hepatocytes. Both basal and PAH-dependent expression of a chloramphenicol acetyltransferase expression plasmid containing approximately 3.5 kilobase pairs of the 5'-flanking region of aldh3 (pALDH3.5CAT) were enhanced 3-4-fold by the PKA inhibitor H8 but not by the PKC inhibitor H7 (>20 microM). cAMP analogs, activators of PKA activity, or protein phosphatase inhibitors diminished expression of the reporter gene in a manner identical to the native gene in cultured rat hepatocytes. Using deletion analysis of the pALDH3.5CAT construct, we demonstrated the existence of a negative regulatory region in the 5'-flanking region between -1057 and -991 base pairs which appears to be responsible for the cAMP-dependent regulation of this gene under both basal and PAH-induced conditions. At least two apparently independent mechanisms which involve protein phosphorylation regulate aldh3 expression. One involves function of the Ah receptor which requires PKC protein phosphorylation to positively regulate both aldh3 and cyp1A1 gene expression and the other a cAMP-responsive process which allows PKA activity to negatively regulate expression of aldh3 under either basal or inducible conditions.
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PMID:cAMP-dependent negative regulation of rat aldehyde dehydrogenase class 3 gene expression. 901 60

In this paper, we review the current status of genetic markers for the development of alcohol abuse. Family, twin, half-sibling and adoption studies of alcoholic subjects suggest that the heritability of liability to alcoholism is at least 50%. These findings have fuelled intensive investigation in the fields of neurology, biochemistry, genetics and molecular biology aimed at the identification of markers for the risk of alcoholism. The most promising of these are discussed in detail. Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) polymorphisms, specifically the ADH3*1, ADH2*2, and ALDH2*2 genotypes appear to confer a protective effect against alcoholism, most notably in Oriental subjects. Caucasian alcohol abusers and their first-degree relatives exhibit depressed platelet monoamine oxidase activity, the degree of which is greater in Type II than Type I alcoholics. Electrophysiological characteristics of alcoholics and those at risk for developing alcoholism have also been identified, including the reduced amplitude of the event-related brain potential and, after ethanol ingestion, characteristic EEG alpha-wave activity. Lower platelet adenylate cyclase activity is seen in alcoholics compared to controls, presumably as a result of over-expression of an inhibitory G-protein. Markers related to other signal transduction pathways of the central nervous system including the serotoninergic, muscarinic and dopaminergic systems are also discussed. In this group of markers, the putative association between the inheritance of the AI allele of the D2 dopamine receptor and the susceptibility to alcoholism provides the most dramatic illustration of the challenges presently existing in this field of scientific investigation. Current limitations in the definition, diagnosis and classification of alcoholism, the confounding influences of race and gender on association studies, as well as the statistical approach of linkage studies are discussed as they relate to the endeavor to uncover valid genetic markers for the risk of alcoholism.
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PMID:Genetic markers of alcohol abuse. 911 63

Given the spectacular advances of genetics during the last five years, it seems appropriate to revisit the important subject of genetics of alcoholism and substance abuse. In recent studies alcohol abuse was shown to have an hereditability of roughly 38%, whereas psychostimulant and opiate use exhibit hereditabilities of 11 to 45%. The hereditability of smoking was found to be around 50%. There is a strong comorbidity between alcoholism and smoking. More than 80% of alcoholics smoke cigarettes in the U.S.A. Other genetic methods such as linkage analysis, allele sharing methods, association studies and analysis of inbred, transgenic and gene-knockout rodents, have partially agreed in showing that the 5HT-1B serotonin receptor and the DRD1, DRD2 and DRD4 dopamine receptors, as well as the dopamine transporter DAT, play an important role in behaviors related to alcoholism and substance abuse. Some neurochemical markers, as for example monoamine oxidase and adenylate cyclase have also been implicated in addictive disorders. The aldehyde dehydrogenase allele ALDH2*2 has a protective effect against alcoholism. Two whole genome linkage studies have shown linkage to chromosomal regions that are in the proximity of the DRD4 dopamine receptor, the GABA receptor gene cluster and the alcohol dehydrogenase gene cluster.
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PMID:[Genetics of addictive disorders]. 1134 17

The formation of glycerol-3-phosphate (G3P) in cells growing on TB causes catabolite repression, as shown by the reduction in malT expression. For this repression to occur, the general proteins of the phosphoenolpyruvate-dependent phosphotransferase system (PTS), in particular EIIA(Glc), as well as the adenylate cyclase and the cyclic AMP-catabolite activator protein system, have to be present. We followed the level of EIIA(Glc) phosphorylation after the addition of glycerol or G3P. In contrast to glucose, which causes a dramatic shift to the dephosphorylated form, glycerol or G3P only slightly increased the amount of dephosphorylated EIIA(Glc). Isopropyl-beta-D-thiogalactopyranoside-induced overexpression of EIIA(Glc) did not prevent repression by G3P, excluding the possibility that G3P-mediated catabolite repression is due to the formation of unphosphorylated EIIA(Glc). A mutant carrying a C-terminally truncated adenylate cyclase was no longer subject to G3P-mediated repression. We conclude that the stimulation of adenylate cyclase by phosphorylated EIIA(Glc) is controlled by G3P and other phosphorylated sugars such as D-glucose-6-phosphate and is the basis for catabolite repression by non-PTS compounds. Further metabolism of these compounds is not necessary for repression. Two-dimensional polyacrylamide gel electrophoresis was used to obtain an overview of proteins that are subject to catabolite repression by glycerol. Some of the prominently repressed proteins were identified by peptide mass fingerprinting. Among these were periplasmic binding proteins (glutamine and oligopeptide binding protein, for example), enzymes of the tricarboxylic acid cycle, aldehyde dehydrogenase, Dps (a stress-induced DNA binding protein), and D-tagatose-1,6-bisphosphate aldolase.
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PMID:Glycerol-3-phosphate-induced catabolite repression in Escherichia coli. 1200 46