Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
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Target Concepts:
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Query: EC:2.3.3.1 (
citrate synthase
)
4,488
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Excitatory mediated neuronal injury has been shown to involve a complex cascade of events. However, the associated cardiac damage reported in humans and marine animals following exposure to excitotoxins has not been well characterized. We hypothesized that the excitotoxin domoic acid can traverse cardiac cell membranes and elicit a deleterious effect on cardiac mitochondrial energetics. Domoic acid (0.05-0.25 microM; 10 min) treatment of isolated rat cardiac mitochondria produced a marked decrease of both mitochondrial flavin adenine dinucleotide (FAD)- and nicotinamide adenine linked respiratory control indices (p < 0.001). Enzymatic assays of the mitochondrial electron transport chain (complexes I-V) and the mitochondrial matrix marker enzyme
citrate synthase
, showed marked concentration-dependent impairment in activity and integrity following exposure to domoic acid (p < 0.01). Similar mitochondrial effects were seen following exposure to the
glutamic acid
analog, kainic acid (0.5-2 microM). Domoic acid (0.05-10 microM; 40 min) was shown by competitive enzyme-linked immunosorbent assay to traverse the cellular membrane of H9c2 rat cardiac myoblasts. Exposure of intact H9c2 cells to domoic acid (10 microM; 24 h) impaired complex II-III activity but did not compromise cellular viability as assessed using cell quantification or lactate dehydrogenase leakage assays. Assessment of reactive oxygen species (superoxide and hydrogen peroxide) production in both isolated cardiac mitochondria and H9c2 cardiomyocytes failed to show any significant differences following exposure to domoic acid (0.05-5 microM). This is the first study to demonstrate a direct effect of domoic acid on cardiac mitochondrial energetics. However, the absence of substantial damage to intact cardiomyocytes raises questions regarding direct toxicological effects on cardiac energetics or viability under conditions of natural domoic acid exposure.
...
PMID:Domoic acid impairment of cardiac energetics. 1859 25
In the 1980s, Shiio and coworkers demonstrated using random mutagenesis that the following three phenotypes were effective for boosting lysine production by Corynebacterium glutamicum: (1) low-activity-level
citrate synthase
(CS
L
), (2) phosphoenolpyruvate carboxylase (PEPC) resistant to feedback inhibition by aspartic acid (PEPC
R
), and (3) pyruvate kinase (PYK) deficiency. Here, we reevaluated these phenotypes and their interrelationship in lysine production using recombinant DNA techniques.The pyk deletion and PEPC
R
(D299N in ppc) independently showed marginal effects on lysine production, but both phenotypes synergistically increased lysine yield, demonstrating the importance of PEPC as an anaplerotic enzyme in lysine production. Similar effects were also found for
glutamic acid
production. CS
L
(S252C in gltA) further increased lysine yield. Thus, using molecular techniques, the combination of these three phenotypes was reconfirmed to be effective for lysine production. However, a simple CS
L
mutant showed instabilities in growth and lysine yield.Surprisingly, the pyk deletion was found to increase biomass production in wild-type C. glutamicum ATCC13032 under biotin-sufficient conditions. The mutant showed a 37% increase in growth (based on OD
660
) compared with the ATCC13032 strain in a complex medium containing 100 g/L glucose. Metabolome analysis revealed the intracellular accumulation of excess precursor metabolites. Thus, their conversion into biomass was considered to relieve the metabolic distortion in the pyk-deleted mutant. Detailed physiological studies of various pyk-deleted mutants also suggested that malate:quinone oxidoreductase (MQO) is important to control both the intracellular oxaloacetic acid (OAA) level and respiration rate. These findings may facilitate the rational use of C. glutamicum in fermentation industries.
...
PMID:Boosting Anaplerotic Reactions by Pyruvate Kinase Gene Deletion and Phosphoenolpyruvate Carboxylase Desensitization for Glutamic Acid and Lysine Production in Corynebacterium glutamicum. 2787 61
The occurrence of Mediterranean fever with periods of increase and decrease has been recorded in the Crimean peninsula. The city of Sevastopol and its vicinity are known endemic areas for this disease. Some of the most active agents in the spread of this rickettsiosis are feral and abandoned dogs. The aim of this study was to test ticks parasitizing dogs in Sevastopol for the presence of
Rickettsia
using molecular methods. The testing of ticks was carried out using real-time PCR and the 'Real Best DNA Rickettsia species' kit (AO 'Vector-Best') followed by sequence identification of the rickettsial DNA detected. The DNA marker for
Rickettsia
species (a conservative area of
citrate synthase
gene,
glt
A) was detected in 16 of 84 (19.1%) samples of
Rhipicephalus sanguineus
ticks tested. Larger fragments of
glt
A,
omp
A and
sca
4 were amplified and sequenced for 10 of 16 PCR-positive samples.
Rickettsia
DNA amplified from eight of the samples matched the sequence of
Rickettsia conorii conorii
Malish, the causative agent of Mediterranean fever. The sequences of
Rickettsia
DNA from two other ticks had the closest match to homologous fragments of
Rickettsia massiliae
, a pathogenic spotted fever rickettsia that was identified in the Crimean Peninsula for the first time as part of this study. The detection of two pathogenic species of
Rickettsia
in the studied ticks suggests the potential for two rickettsial diseases in the region and warrants further epidemiological and clinical studies.
...
PMID:The role of
Rhipicephalus sanguineus
ticks parasitizing dogs in the spread of tick-borne rickettsial pathogens in the city of Sevastopol. 3257 90
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