Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Marked activity of cobalt-activated acylase was found in the sera of 33 of 37 patients with acute toxic hepatitis due to poisoning with either amanita mushrooms or chemicals. The activity of the enzyme showed a positive correlation with that of serum transaminases, reached the highest levels on the patient's admission to hospital and within a few days fell rapidly to undetectable levels. Slight acylase activity was observed in the majority of patients intoxicated with drugs or carbon monoxide but was not seen in sera of those poisoned with non-amanita mushrooms who showed no signs of liver injury. Unlike acylase, the serum activity of gamma-glutamyl transpeptidase remained unchanged over the first days of acute toxic hepatitis. The determination of serum cobalt-activated acylase might be of value in the diagnosis of acute liver injury.
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PMID:Serum cobalt-activated acylase and gamma-glutamyl transpeptidase activities in toxic hepatitis. 24 82

Cobalt-activated acylase (Co-A) and transaminase activity were determined in the serum of A/Jax, DBA/2 and C3H mice several days after an intraperitoneal injection of 1,000 lethal doses of murine hepatitis virus type 3 (MHV3). A significant rise in the enzyme activity was observed 1 day after the injection, followed by a decrease on day 2. In the case of the genetically resistant A/Jax strain, the Co-A level regularly decreased to reach normal values on days 7-8. On the contrary, among the fully susceptible DBA/2 strain mice (all dead on day 5), a second rise in acylase (Co-A) level was observed on days 3 and 4, much higher than the day-1 values. Among the mice of C3H strain, which is recorded as 'semi-susceptible', some individuals behaved like the susceptible DBA/2. The comparison of serum acylase activity with other liver function tests showed a correlation between Co-A and transaminases (ALT and AST) with C3H and DBA/2 strains, but no correlation with A/JAX resistant strain. gamma-Glutamyltransferase was not detectable in the serum of different strains during the time of experimentations. Our results suggest that Co-A activity correlates with the clinical course, and that Co-A is a sensitive indicator enzyme in the early phase of viral hepatitis.
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PMID:A genetic study of serum levels of cobalt-activated acylase among susceptible, resistant and semiresistant strains of mice with experimental viral hepatitis. 715 76

Double-stranded (ds) RNA-specific adenosine deaminase converts adenosine residues into inosines in dsRNA and edits transcripts of certain cellular and viral genes such as glutamate receptor (GluR) subunits and hepatitis delta antigen. The first member of this type of deaminase, DRADA1, has been recently cloned based on the amino acid sequence information derived from biochemically purified proteins. Our search for DRADA1-like genes through expressed sequence tag databases led to the cloning of the second member of this class of enzyme, DRADA2, which has a high degree of sequence homology to DRADA1 yet exhibits a distinctive RNA editing site selectivity. There are four differentially spliced isoforms of human DRADA2. These different isoforms of recombinant DRADA2 proteins, including one which is a human homolog of the recently reported rat RED1, were analyzed in vitro for their GluR B subunit (GluR-B) RNA editing site selectivity. As originally reported for rat RED1, the DRADA2a and -2b isoforms edit GluR-B RNA efficiently at the so-called Q/R site, whereas DRADA1 barely edits this site. In contrast, the R/G site of GluR-B RNA was edited efficiently by the DRADA2a and -2b isoforms as well as DRADA1. Isoforms DRADA2c and -2d, which have a distinctive truncated shorter C-terminal structure, displayed weak adenosine-to-inosine conversion activity but no editing activity tested at three known sites of GluR-B RNA. The possible role of these DRADA2c and -2d isoforms in the regulatory mechanism of RNA editing is discussed.
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PMID:Editing of glutamate receptor B subunit ion channel RNAs by four alternatively spliced DRADA2 double-stranded RNA adenosine deaminases. 911 10

RNA editing catalyzed by ADAR1 and ADAR2 involves the site-specific conversion of adenosine to inosine within imperfectly duplexed RNA. ADAR1- and ADAR2-mediated editing occurs within transcripts of glutamate receptors (GluR) in the brain and in hepatitis delta virus (HDV) RNA in the liver. Although the Q/R site within the GluR-B premessage is edited more efficiently by ADAR2 than it is by ADAR1, the converse is true for the +60 site within this same transcript. ADAR1 and ADAR2 are homologs having two common functional regions, an N-terminal double-stranded RNA-binding domain and a C-terminal deaminase domain. It is neither understood why only certain adenosines within a substrate molecule serve as targets for ADARs, nor is it known which domain of an ADAR confers its specificity for particular editing sites. To assess the importance of several aspects of RNA sequence and structure on editing, we evaluated 20 different mutated substrates, derived from four editing sites, for their ability to be edited by either ADAR1 or ADAR2. We found that when these derivatives contained an A:C mismatch at the editing site, editing by both ADARs was enhanced compared to when A:A or A:G mismatches or A:U base pairs occurred at the same site. Hence substrate recognition and/or catalysis by ADARs could involve the base that opposes the edited adenosine. In addition, by using protein chimeras in which the deaminase domains were exchanged between ADAR1 and ADAR2, we found that this domain played a dominant role in defining the substrate specificity of the resulting enzyme.
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PMID:Substrate recognition by ADAR1 and ADAR2. 1142 61

Hepatitis delta virus (HDV) is a subviral human pathogen that uses specific RNA editing activity of the host to produce two essential forms of the sole viral protein, hepatitis delta antigen (HDAg). Editing at the amber/W site of HDV antigenomic RNA leads to the production of the longer form (HDAg-L), which is required for RNA packaging but which is a potent trans-dominant inhibitor of HDV RNA replication. Editing in infected cells is thought to be catalyzed by one or more of the cellular enzymes known as adenosine deaminases that act on RNA (ADARs). We examined the effects of increased ADAR1 and ADAR2 expression on HDV RNA editing and replication in transfected Huh7 cells. We found that both ADARs dramatically increased RNA editing, which was correlated with strong inhibition of HDV RNA replication. While increased HDAg-L production was the primary mechanism of inhibition, we observed at least two additional means by which ADARs can suppress HDV replication. High-level expression of both ADAR1 and ADAR2 led to extensive hyperediting at non-amber/W sites and subsequent production of HDAg variants that acted as trans-dominant inhibitors of HDV RNA replication. Moreover, we also observed weak inhibition of HDV RNA replication by mutated forms of ADARs defective for deaminase activity. Our results indicate that HDV requires highly regulated and selective editing and that the level of ADAR expression can play an important role: overexpression of ADARs inhibits HDV RNA replication and compromises virus viability.
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PMID:Increased RNA editing and inhibition of hepatitis delta virus replication by high-level expression of ADAR1 and ADAR2. 1190 22

The DNA deaminase family encompasses enzymes that have been highly conserved throughout vertebrate evolution and which display wide-ranging positive effects upon innate and adaptive immune system and development. Activation-induced cytidine deaminase was identified as a DNA mutator after its necessity in the successful development of high-affinity B cells via somatic hypermutation, class switch recombination, and gene conversion was determined. APOBEC3 exhibits the ability to deaminate retroviral first strand cDNA in a variety of viral infections, including HIV and hepatitis. Recent work has highlighted the potential importance of activation-induced cytidine deaminase (AID) and APOBEC1 in epigenetic reprogramming, and also the role that AID and the APOBECs may have in the development of cancer. In addition to the known activities of these members of the protein family, there are still other deaminases, such as APOBEC2, whose targets and functions are as yet unknown. This chapter provides the details of two assays that have proved to be invaluable in elucidating the exact specificities of deaminases both in vitro and in Escherichia coli. The application of these assays to future studies of the deaminase family will provide an indispensible tool in determining the potentially diverse functions of the remainder of this family of enzymes.
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PMID:Genetic and in vitro assays of DNA deamination. 1679 68

The RNA-editing enzyme ADAR1 is a double-stranded RNA (dsRNA) binding protein that modifies cellular and viral RNA sequences by adenosine deamination. ADAR1 has been demonstrated to play important roles in embryonic erythropoiesis, viral response, and RNA interference. In human hepatitis virus infection, ADAR1 has been shown to target viral RNA and to suppress viral replication through dsRNA editing. It is not clear whether this antiviral effect of ADAR1 is a common mechanism in response to viral infection. Here, we report a proviral effect of ADAR1 that enhances replication of vesicular stomatitis virus (VSV) through a mechanism independent of dsRNA editing. We demonstrate that ADAR1 interacts with dsRNA-activated protein kinase PKR, inhibits its kinase activity, and suppresses the alpha subunit of eukaryotic initiation factor 2 (eIF-2alpha) phosphorylation. Consistent with the inhibitory effect on PKR activation, ADAR1 increases VSV infection in PKR+/+ mouse embryonic fibroblasts; however, no significant effect was found in PKR-/- cells. This proviral effect of ADAR1 requires the N-terminal domains but does not require the deaminase domain. These findings reveal a novel mechanism of ADAR1 that increases host susceptibility to viral infection by inhibiting PKR activation.
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PMID:Double-stranded RNA deaminase ADAR1 increases host susceptibility to virus infection. 1707 86

Cytosolic enzymes AMP deaminase and adenosine deaminase (ADA) catalyze AMP and adenosine deamination, constitute rate-limiting steps of adenine nucleotide catabolism and play important roles in cellular energy metabolism. In this study, AMP deaminase and ADA activities of rat liver, neocortex, cerebellum, striatum and hippocampus were investigated in acute ammonia intoxication and subacute CCl(4)-induced hepatitis. Activities of both AMP deaminase and ADA in the liver were elevated by 2.4-4.2-fold (p<0.0001) in both models of hepatotoxic injury as compared with controls. In acute hyperammonemia activities of AMP, deaminase and ADA increased by 46-59% (p<0.02) in the neocortex and did not change in the striatum. In the hippocampus of hyperammonemic rats, only AMP deaminase activity was increased by 48% (p=0.0004), and in the cerebellum only ADA activity was increased significantly (by 26%, p<0.05). The adenylate pool size and energy charge were greatly reduced in the neocortex of hyperammonemic rats. Results suggested that two parallel pathways of AMP breakdown, including AMP deaminase and ADA, respectively, are up-regulated under pathological conditions, probably in order to overcome compensatory synthesis of adenylates, to ensure prompt adenylate pool depletion and reduce the adenylate energy charge in liver and selected brain regions.
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PMID:AMP deaminase and adenosine deaminase activities in liver and brain regions in acute ammonia intoxication and subacute toxic hepatitis. 1990 Apr 20

Adenosin deaminase (ADA) deficiency is the cause for Severe Combined Immunodeficiency (SCID) in about 15% of patients with SCID, often presenting as T (-)B (-)NK (-)SCID. Treatment options for ADA-SCID are enzyme replacement, bone marrow transplantation or gene therapy. We here describe the first patient with ADA-SCID and fatal hepatic failure despite bone marrow transplantation from a 10/10 HLA identical related donor. As patients with ADA-SCID may be at yet underestimated increased risk for rapid hepatic failure we speculate whether hepatitis in ADA-SCID should lead to the immediate treatment with enzyme replacement by pegylated ADA.
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PMID:Hyperbilirubinemia and rapid fatal hepatic failure in severe combined immunodeficiency caused by adenosine deaminase deficiency (ADA-SCID). 2127 5