Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Biotin deficiency in Aspergillus nidulans resulted in a 70% increase of the protein content and increased levels of free and bound aspartate, glutamate, serine, leucine and methionine. Likewise, the activities of NADP+ glutamate dehydrogenase, NAD+ gluatmate dehydrogenase, aspartate aminotransferase and alanine aminotransferase were significantly increased. The total RNA content increased while the DNA content was unaffected. The rRNA/tRNA ratio remained higher in biotin-deficient cells. Supplementation of glutamate, aspartate, serine, leucine and methionine to the culture medium raised the rRNA/tRNA ratio, and the difference observed in the qualitative and the quantitative patterns of protein and dry cell mass between normal and biotin-deficient cultures was abolished.
 ...
PMID:Factors affecting protein synthesis during biotin deficiency in Aspergillus nidulans. 4 77

1. The effect of elongation factor 2 (EF 2) and of adenosine diphosphate-ribosylated elongation factor 2 (ADP-ribosyl-EF 2) on the shift of endogenous peptidyl-tRNA from the A to the P site of rat liver ribosomes (measured by the peptidyl-puromycin reaction) and on the release of deacylated tRNA (measured by aminoacylation) was investigated. 2. Limiting amounts of EF2, pre-bound or added to ribosomes, catalyse the shift of peptidyl-tRNA in the presence of GPT; when the enzyme is added in substrate amounts GMP-P(CH2)P [guanosine (beta, gamma-methylene)triphosphate] can partially replace GTP. ADP-ribosyl-EF 2 has no effect on the shift of peptidyl-tRNA when present in catalytic amounts, but becomes almost as effective as EF 2 when added in substrate amounts together with GTP; GMP-P(CH2)P cannot replace GTP. 3. The release of deacylated tRNA is induced only by substrate amounts of added EF 2 and also occurs in the absence of guanine nucleotides. In this reaction ADP-ribosyl-EF 2 is only 25% as effective as EF 2 in the absence of added nucleotide, but becomes 60-80% as effective in the presence of GTP or GMP-P(CH2)P. 4. The results obtained on protein-synthesizing systems are consistent with the hypothesis that ADP-ribosyl-EF 2 can operate a single round of translocation followed by binding of aminoacyl-tRNA and peptide-bond formation. 5. From the data obtained with the native enzyme it is concluded that the two moments of translocation require different conditions of interaction of EF 2 with ribosomes; it is suggested that the shift of peptidyl-tRNA is catalysed by EF 2 pre-bound to ribosomes, and that the release of tRNA is induced by a second molecule of interacting EF 2. The hydrolysis of GTP would be required for the release of pre-bound EF 2 from ribosomes. 5. The inhibition of the utilization of limiting amounts of EF 2 on ADP-ribosylation is very likely the consequence of a concomitant decrease in the rate of association and dissociation of the enzyme from ribosomes.
 ...
PMID:Effect of elongation factor 2 and of adenosine diphosphate-ribosylated elongation factor 2 on translocation. 18 40

The involvement of the first 69 amino acids of eukaryotic elongation factor 1 alpha (EF-1 alpha) from rabbit reticulocyte in GTP and aminoacyl-tRNA binding has been analyzed by a variety of techniques. EF-1 alpha was subjected to limited trypsin digestion, which cleaved predominantly at residues 36 and 69. A digested form of Escherichia coli EF-Tu, similar to the one used for this study, has been characterized by x-ray crystallography and is used as a structural model for EF-1 alpha. This form of EF-1 alpha bound E. coli Phe-tRNAPhe similar to the wild type protein, but lacked activity in phenylalanine polymerization with poly(U)-programmed ribosomes. These results were obtained regardless of whether or not loosely associated N-terminal peptides were removed by gel filtration chromatography. The digested EF-1 alpha also shows reduced GTPase activity, but the activity is stimulated by both ribosomes and aminoacyl-tRNA. Binding of EF-1 alpha to the 80 S ribosome, as determined by association of reductively methylated protein through Sepharose 6B chromatography, is reduced approximately 7-fold for the limited digested form of the protein. Limited digested EF-1 alpha can, however, be photo-cross-linked with GTP and 3'-p-azido-GTP similar to intact EF-1 alpha. Chemical cross-linking with oxidized GTP, fluorosulfonylbenzoyl-GTP, or with trans-diaminedichloroplatinum(II) and GPT, shows a similar modification of both intact and limited digested EF-1 alpha. In order to further localize the modification site with the GTP reagents and assure that modification was not occurring in the first 69 amino acids, intact EF-1 alpha was modified with these same reagents. Limited trypsin digestion of modified protein indicates that none of these reagents cross-links GTP to the first 69 amino acids of EF-1 alpha, which includes the first GTP binding consensus element, GXXXXGK.
 ...
PMID:Characterization of a limited trypsin digestion form of eukaryotic elongation factor 1 alpha. 199 4

Several modified nucleosides were introduced during in vitro RNA synthesis into a pre-tRNA(Ser). The pre-tRNAs were used as substrates for RNase P enzymes. No effects were observed with biotin-8-ATP or [alpha-S]-GPT, whereas with m7GTP, the cleavage reaction was completely inhibited. Analysis of pre-tRNAs which contained m7G at various positions has revealed a single base at the 5'-end of the acceptor stem where this modification absolutely prevents cleavage by catalytic M1 RNA, eukaryotic and prokaryotic RNase P holoenzymes. These results suggest that a critical contact must be made between pre-tRNA substrate and enzyme/ribozyme or that the approach of the potential cleaving agent (a positive magnesium ion) is made impossible by the positive charge at N-7 of the guanosine. In addition, we have shown that a pre-tRNA containing only m7G's can still form a complex with M1 RNA in a gel retardation assay.
 ...
PMID:The methylation of one specific guanosine in a pre-tRNA prevents cleavage by RNase P and by the catalytic M1 RNA. 217 70

The translocation of the messenger RNA relative to the ribosome during peptide synthesis represents an example of a mechano-chemical reaction in which the chemical bond energy of GTP is transformed into coordinated motion. Such transformations also occur during the beating of cilia and flagellae, the contraction of muscle and the migration of chromosomes in cell division. In protein synthesis the functional geometric and energetic conditions for this transformation are well defined. For each peptide bond formed, the ribosome moves one codon along the mRNA (towards the 3' end) and one molecule of GTP is hydrolysed. Although the basic requirements of this reaction have been elucidated, the mechanism is still unresolved. We demonstrate here that translocation can be analysed as a series of binding equilibria shifted by one irreversible, GTP-consuming step. The shift in the binding equilibrium is induced by the transfer of the peptidyl moiety to the (A) site-bound aminoacyl (AA)-tRNA. This results in the A site-bound tRNA having an increased affinity for the high-affinity (P) site, and a strengthened association with the mRNA. Elongation factor (EF) G . GPT catalyses removal of the deacylated tRNA, empties the P site and at the same time loosens ribosome-mRNA association. The result of these changes is that peptidyl(PP)-tRNA . mRNA is shifted from the A site to the P site, binding of AA-tRNA . EF-Tu . GPT to the vacant A site ensuring that the process is irreversible.
 ...
PMID:Steps of mRNA translocation in protein biosynthesis. 702 51

RNA, DNA, total protein, transketolase (TK), alanine aminotransferase (AlAT), aspartate aminotransferase (AsAT), methionyl-tRNA (met-tRNA)- and cysteinyl-tRNA (cys-tRNA)-synthetases in the thymus and spleen of 46 intact rats exposed to hypokinesia and vitamin B1 deficiency were measured. It was found that 15-day hypokinesia induced a significant decrease of the thymus and spleen weight and an increase of AlAT in the thymus. Vitamin B1 deficiency (hydroxy thiamine in drinking water at a dose of 2 mg/kg body weight for 15 days) led to a substantial decrease of TK in blood, AlAT and AsAT in the spleen; it diminished AsAT and increased AlAT in the thymus. Combined exposure to hypokinesia and vitamin B1 deficiency caused a more marked decrease of the weight of lymph organs, a significant loss of body weight, an increase of DNA in the thymus and spleen, and an increase of TK, met-tRNA-synthetase and AlAT in the thymus. These results suggest that vitamin B1 deficiency aggravates disorders in protein and nucleic acid metabolism in the lymph organs of hypokinetic animals.
 ...
PMID:[Several indicators of protein and nucleic acid metabolism in lymphoid organs of rats exposed to hypokinesia and vitamin B1 deficiency]. 857 40

A 40-year-old Chinese-American woman with breast carcinoma metastatic to her lungs presented with a 3-month history of erosions on her inner thighs (Figure 1) and medial left shoulder. Faint livedo reticularis was evident on her legs as well. She had difficulty in walking and raising her shoulders. Her cutaneous examination was also notable for cuticular erythema (Figure 2) and mild periorbital erythema and edema. She had no systemic or rheumatologic complaints other than some difficulty in swallowing. Her blood chemistry values were notable for a creatinine kinase of 564 IU/L (5-200 IU/L), alanine aminotransferase 161 U/L (0-40 U/L) and aspartate aminotransferase 93 U/L (0-40 U/L), and an antinuclear antibody titer of 1:2560. Other blood chemistries and antibody serologies (anti-Jo-1, anti-Mi-2 and other anti-tRNA synthetase, anti-Ro/SSA, anti-U1RNP, anti-PM/Scl, and anti-Ku) were within normal limits. A biopsy specimen was obtained from an area of intact skin close to a right thigh ulceration that showed subtle vacuolar alteration at the dermo-epidermal junction with occasional necrotic keratinocyte (Figure 3). Melanophages and telangiectases were present. Within the subcutis there was fibrin deposition and neutrophils. A diagnosis of dermatomyositis was made. The patient received oral prednisone 20 mg three times a day, and her ulcerations resolved. Her creatinine kinase, alanine aminotransferase, and aspartate aminotransferase values returned to normal over the course of 3 weeks, but her antinuclear antibody was unchanged. Radiographic studies concurrently noted that her breast cancer had recurred in her lungs; plans were made to treat her with chemotherapy. The patient was lost to close follow-up, but it was learned that her erosions had reoccurred while her prednisone was tapered and resolved when her dosage of prednisone was increased.
 ...
PMID:Ulcerative paraneoplastic dermatomyositis secondary to metastatic breast cancer. 1660 44

Drug-induced liver injury (DILI) is the primary adverse event that results in the withdrawal of drugs from the market and a frequent reason for the failure of drug candidates in the pre-clinical or clinical phases of drug development. This paper presents an approach for identifying potential liver toxicity genomic biomarkers from a liver toxicity biomarker study involving the paired compounds entacapone ("non-liver toxic drug") and tolcapone ("hepatotoxic drug"). Molecular analysis of the rat liver and plasma samples, combined with statistical analysis, revealed many similarities and differences between the in vivo biochemical effects of the two drugs. Six hundred and ninety-five genes and 61 pathways were selected based on the classification scheme. Of the 61 pathways, 5 were specific to treatment with tolcapone. Two of the 12 animals in the tolcapone group were found to have high ALT, AST, or TBIL levels. The gene Vars2 (valyl-tRNA synthetase 2) was identified in both animals and the pathway to which it belongs, the aminoacyl-tRNA biosynthesis pathway, was one of the three most significant tolcapone-specific pathways identified.
 ...
PMID:Identification and categorization of liver toxicity markers induced by a related pair of drugs. 2184 99