INT28926

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Context Info
Confidence 0.58
First Reported 1989
Last Reported 2010
Negated 0
Speculated 0
Reported most in Abstract
Documents 11
Total Number 11
Disease Relevance 1.25
Pain Relevance 1.97

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

mitochondrion (Aldh2) oxidoreductase activity (Aldh2)
Anatomy Link Frequency
liver 1
Aldh2 (Rattus norvegicus)
Pain Link Frequency Relevance Heat
tolerance 102 98.76 Very High Very High Very High
headache 69 98.32 Very High Very High Very High
addiction 30 94.28 High High
Angina 9 87.20 High High
Enkephalin 7 83.68 Quite High
alcohol 17 72.56 Quite High
Neuropeptide 1 57.60 Quite High
Pain 16 32.84 Quite Low
Migraine 10 26.00 Quite Low
analgesia 14 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Headache 77 98.32 Very High Very High Very High
Myocardial Infarction 3 88.00 High High
Cv General 3 Under Development 9 87.20 High High
Increased Venous Pressure Under Development 23 68.24 Quite High
Vomiting 1 62.88 Quite High
Volume Depletion And Dehydration 6 40.80 Quite Low
Loss Of Sense Of Smell 1 34.32 Quite Low
Pain 16 32.84 Quite Low
Photophobia 2 21.68 Low Low
Poisoning 1 11.76 Low Low

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
However, the mitochondrial aldehyde dehydrogenase (ALDH2) is inhibited in GTN-tolerant tissues and produces NO2- from GTN, which is proposed to be converted to NO within mitochondria.
Negative_regulation (inhibited) of ALDH2
1) Confidence 0.58 Published 2003 Journal Mol. Pharmacol. Section Abstract Doc Link 14573760 Disease Relevance 0.17 Pain Relevance 0.29
The in vivo protocol resulted in almost complete inhibition of ALDH2 activity and GTN biotransformation in hepatic mitochondria, indicating that long-term GTN exposure results in inactivation of the enzyme.
Negative_regulation (inhibition) of ALDH2
2) Confidence 0.58 Published 2003 Journal Mol. Pharmacol. Section Abstract Doc Link 14573760 Disease Relevance 0.20 Pain Relevance 0.29
However, the mitochondrial aldehyde dehydrogenase (ALDH2) is inhibited in GTN-tolerant tissues and produces NO2- from GTN, which is proposed to be converted to NO within mitochondria.
Negative_regulation (inhibited) of mitochondrial aldehyde dehydrogenase
3) Confidence 0.58 Published 2003 Journal Mol. Pharmacol. Section Abstract Doc Link 14573760 Disease Relevance 0.18 Pain Relevance 0.29
In the presence of dithiothreitol (DTT) inactivation of ALDH2 was much
slower. 
Negative_regulation (inactivation) of ALDH2
4) Confidence 0.53 Published 2008 Journal The Journal of Biological Chemistry Section Abstract Doc Link PMC2576553 Disease Relevance 0 Pain Relevance 0.04
These
observations are consistent with a significant role for irreversible
inactivation of ALDH2 in the development of nitrate tolerance.



Negative_regulation (inactivation) of ALDH2 associated with tolerance
5) Confidence 0.39 Published 2008 Journal The Journal of Biological Chemistry Section Abstract Doc Link PMC2576553 Disease Relevance 0 Pain Relevance 0.05
Accordingly, inactivation of ALDH2 seems to be due to
the oxidation and subsequent disulfide formation of an essential cysteine
residue. 
Negative_regulation (inactivation) of ALDH2
6) Confidence 0.39 Published 2008 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2576553 Disease Relevance 0 Pain Relevance 0
Both L-arginine and L-proline, the two amino acids component of kentsin, decreased the specific activity of rat liver mitochondrial aldehyde dehydrogenase in vitro at 10(-3) mol concentration.
Negative_regulation (decreased) of mitochondrial aldehyde dehydrogenase in liver
7) Confidence 0.37 Published 1989 Journal Physiol. Behav. Section Abstract Doc Link 2813554 Disease Relevance 0 Pain Relevance 0.53
Importantly, ALDH2-catalyzed GTN
reduction was partly inactivated by preincubation with GTN, suggesting that
the inactivation of GTN reduction is also partly irreversible. 
Negative_regulation (reduction) of ALDH2-catalyzed
8) Confidence 0.34 Published 2008 Journal The Journal of Biological Chemistry Section Abstract Doc Link PMC2576553 Disease Relevance 0 Pain Relevance 0
One major unresolved question
concerns the identity of the physiological reductant, because ALDH2-catalyzed
GTN reduction is supported by the non-physiological thiol dithiothreitol (DTT)
but not by glutathione (GSH), the most abundant physiological low-molecular
weight thiol. 
Negative_regulation (reduction) of ALDH2-catalyzed
9) Confidence 0.34 Published 2008 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2576553 Disease Relevance 0.12 Pain Relevance 0.05
FIGURE 7.Effect of preincubation of ALDH2 with GTN on the ALDH2-catalyzed
reduction of GTN. 
Negative_regulation (reduction) of ALDH2-catalyzed
10) Confidence 0.34 Published 2008 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2576553 Disease Relevance 0 Pain Relevance 0
This suggests that the headache experienced after the combination of ethanol and disulfiram and in individuals who lack functional ALDH-2 is not due to the same mechanism as the hangover headache experienced in the absence of disulfiram.
Negative_regulation (lack) of ALDH-2 associated with headache
11) Confidence 0.30 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3013144 Disease Relevance 0.58 Pain Relevance 0.43

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