INT97453

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Context Info
Confidence 0.04
First Reported 2001
Last Reported 2010
Negated 0
Speculated 1
Reported most in Body
Documents 25
Total Number 26
Disease Relevance 13.40
Pain Relevance 2.40

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

cytosol (MOCS1) small molecule metabolic process (MOCS1) nucleus (MOCS1)
Anatomy Link Frequency
nervous systems 2
macrophage 1
endothelial cell 1
fibroblasts 1
PGE2 1
MOCS1 (Homo sapiens)
Pain Link Frequency Relevance Heat
Catechol-O-methyltransferase 218 99.62 Very High Very High Very High
antagonist 32 99.44 Very High Very High Very High
Paracetamol 1 99.00 Very High Very High Very High
Fibrositis 4 98.80 Very High Very High Very High
Inflammation 48 95.96 Very High Very High Very High
Pain 67 95.48 Very High Very High Very High
agonist 3 95.16 Very High Very High Very High
melanocortin 1 receptor 2 94.28 High High
Morphine 2 93.84 High High
Cancer pain 2 93.00 High High
Disease Link Frequency Relevance Heat
Gauchers Disease 500 99.88 Very High Very High Very High
Pathologic Processes 6 99.72 Very High Very High Very High
Targeted Disruption 17 99.20 Very High Very High Very High
Sleep Disorders 4 98.80 Very High Very High Very High
Skin Cancer 2 98.52 Very High Very High Very High
Temporomandibular Joint Disorders 10 97.80 Very High Very High Very High
Lysosome Storage Disease 21 97.40 Very High Very High Very High
Insulin Resistance 33 97.24 Very High Very High Very High
Diabetes Mellitus 133 96.60 Very High Very High Very High
Hypertension 27 96.44 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
An inherited deficiency of this enzyme activity leads to the onset of Gaucher disease, the most common lysosomal storage disorder.
Negative_regulation (deficiency) of enzyme associated with gauchers disease and lysosome storage disease
1) Confidence 0.04 Published 2006 Journal Biochem. Cell Biol. Section Abstract Doc Link 16609695 Disease Relevance 0.58 Pain Relevance 0.08
On smooth surfaces, AA and PGE2 dose-dependently increased ALP, while on rough surfaces, treatment dose-dependently decreased enzyme specific activity.
Negative_regulation (decreased) of enzyme in PGE2
2) Confidence 0.03 Published 2008 Journal J Oral Implantol Section Abstract Doc Link 19133484 Disease Relevance 0.42 Pain Relevance 0.05
In vitro enzyme activity was slightly reduced by acetyl salicylic and acetaminophen and reduced 50% with amino glycosides and ampicillin antibiotics at concentrations of 0.6 and 30 mg ml(-1), respectively.
Negative_regulation (reduced) of enzyme associated with paracetamol
3) Confidence 0.02 Published 2010 Journal Appl. Biochem. Biotechnol. Section Abstract Doc Link 19902382 Disease Relevance 0 Pain Relevance 0.10
However, increasing mutant enzyme activities with an inhibitor may not be an ideal solution in vivo, as the chaperone action may be functionally compromised by the inhibition of enzyme activity.
Negative_regulation (inhibition) of enzyme
4) Confidence 0.01 Published 2010 Journal Current Chemical Genomics Section Body Doc Link PMC2995157 Disease Relevance 0.85 Pain Relevance 0.03
It has been reported that some enzyme inhibitors and receptor antagonists can serve as chaperones for mutant enzymes and receptors, as they bind to the target protein tightly [33, 34].
Negative_regulation (inhibitors) of enzyme associated with antagonist
5) Confidence 0.01 Published 2010 Journal Current Chemical Genomics Section Body Doc Link PMC2995157 Disease Relevance 0.73 Pain Relevance 0.12
Where enzyme activity was present, EDTA caused >95% decrease in all enzyme activity in the NP and AF (Figure 3a), with the exception of the AF of moderately and severely degenerate IVDs, where it inhibited all caseinase activity (p < 0.01) but only 40% of type II collagenase (p < 0.02) and 70% of gelatinase (p < 0.02) activity.
Negative_regulation (decrease) of enzyme
6) Confidence 0.01 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2206387 Disease Relevance 0 Pain Relevance 0
BSIP eliminated all enzyme activity in every situation.
Negative_regulation (eliminated) of enzyme
7) Confidence 0.01 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2206387 Disease Relevance 0 Pain Relevance 0
The tissue can be pretreated to examine the effects of putative stimulators/inhibitors of enzyme activity.
Spec (examine) Negative_regulation (inhibitors) of enzyme
8) Confidence 0.01 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2206387 Disease Relevance 0 Pain Relevance 0
95% inhibition of enzyme activity in both.
Negative_regulation (inhibition) of enzyme
9) Confidence 0.01 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2206387 Disease Relevance 0.07 Pain Relevance 0
Enzyme inhibitors
Negative_regulation (inhibitors) of Enzyme
10) Confidence 0.01 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2206387 Disease Relevance 0 Pain Relevance 0
Gaucher disease, the deficiency of the lysosomal enzyme glucocerebrosidase: recombinant enzyme therapy
Negative_regulation (deficiency) of enzyme associated with gauchers disease
11) Confidence 0.01 Published 2010 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2909498 Disease Relevance 0.90 Pain Relevance 0.17
Gaucher disease (GD), the inherited deficiency of the lysosomal enzyme glucocerebrosidase ([GC] enzyme commission number EC 3.2.1.45), presents with a wide range of symptoms of varying severity, and primarily affects the skeletal, hematologic and nervous systems.
Negative_regulation (deficiency) of enzyme in nervous systems associated with gauchers disease
12) Confidence 0.01 Published 2010 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2909498 Disease Relevance 0.56 Pain Relevance 0.07
EET has been proposed for a number of lysosomal storage disorders, including GD, Sandhoff, Fabry, and Tay-Sachs diseases.68,69 The mechanism of action for these compounds is competitive binding to the active site of the mutant enzyme, facilitating proper folding and trafficking to the lysosome, where endogenous substrate displaces the chaperone and enzyme activity is restored.70 Most chaperones studied to date are enzyme inhibitors in the structural class of imino sugars or similar analogs of the natural substrate, glucosylceramide.71 Imino sugars have been shown to increase the cellular activity of the N370S mutant form of GC, as well as the wild-type enzyme.72 In cell based systems, where fibroblasts from patients are cultured with the chemical chaperone N-nonyl-deoxynojirimycin, the enzymatic activity of the GC variant, N370S, is increased.
Negative_regulation (inhibitors) of enzyme in fibroblasts associated with gauchers disease, disease and lysosome storage disease
13) Confidence 0.01 Published 2010 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2909498 Disease Relevance 0.59 Pain Relevance 0
The divergent phenotypes and the heterogeneity involving different organ systems implicates the involvement of several pathological processes that include enzyme deficiency, substrate accumulation, protein misfolding, and macrophage activation, that differ in each patient with GD.
Negative_regulation (deficiency) of enzyme in macrophage associated with pathologic processes and gauchers disease
14) Confidence 0.01 Published 2010 Journal Therapeutics and Clinical Risk Management Section Abstract Doc Link PMC2909498 Disease Relevance 0.48 Pain Relevance 0
The future of the treatment of GD will include an individualized approach, employing a combination of therapies that can address the effects of enzyme deficiency, storage of abnormal lipid substrate resulting in lysosomal dysfunction, protein misfolding and the inflammatory processes.



Negative_regulation (deficiency) of enzyme associated with inflammation and gauchers disease
15) Confidence 0.01 Published 2010 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2909498 Disease Relevance 0.63 Pain Relevance 0.05
Optimal therapy in Gaucher disease

Gaucher disease (GD), the inherited deficiency of the lysosomal enzyme glucocerebrosidase, presents with a wide range of symptoms of varying severity, and primarily affects the skeletal, hematologic and nervous systems.

Negative_regulation (deficiency) of enzyme in nervous systems associated with gauchers disease
16) Confidence 0.01 Published 2010 Journal Therapeutics and Clinical Risk Management Section Title Doc Link PMC2909498 Disease Relevance 0.52 Pain Relevance 0
A clear genotype-phenotype correlation could be found [102]: patients with the severe childhood phenotype have mutations that result in absence of enzyme activity, whereas patients with the milder childhood and adult (myopathic) phenotypes have mutations that result in residual enzyme activity.
Negative_regulation (absence) of enzyme
17) Confidence 0.01 Published 2010 Journal Journal of Biomedicine and Biotechnology Section Body Doc Link PMC2877206 Disease Relevance 0.72 Pain Relevance 0.03
Furthermore, functional polymorphisms in the COMT gene resulting in reduced enzyme activity are associated with fibromyalgia [25], [26], temporomandibular disorder (TMD) onset [27], experimental pain sensitivity [27], [28], and altered morphine efficacy in cancer pain treatment [29].
Negative_regulation (reduced) of enzyme associated with pain, catechol-o-methyltransferase, temporomandibular joint disorders, cancer pain, fibrositis and morphine
18) Confidence 0.01 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2664927 Disease Relevance 1.42 Pain Relevance 1.06
Thus, minor SNPs linked to the APS haplotype may compensate for the decreased enzyme thermostability produced by the met158 allele.
Negative_regulation (decreased) of enzyme
19) Confidence 0.01 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2664927 Disease Relevance 0.28 Pain Relevance 0.24
James Shayman and colleagues in the University of Michigan and a former student of Norman Radin identified high-affinity inhibitors of the metabolic target of glycosphingolipid synthesis, UDP-glucyosylceramide synthase.66 Homologues of the most potent inhibitors were generated as highly selective inhibitors of the enzyme, with inhibitory concentrations in the nanomolar range, but without appreciable cytotoxicity in culture.
Negative_regulation (inhibitors) of enzyme
20) Confidence 0.01 Published 2010 Journal Biologics : Targets & Therapy Section Body Doc Link PMC3010821 Disease Relevance 0.37 Pain Relevance 0

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