INT113951

Context Info Confidence 0.13 First Reported 2003 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 2 Total Number 8 Disease Relevance 0.26 Pain Relevance 0.25

signal transduction (Gnat3) GTPase activity (Gnat3) cytoplasm (Gnat3) signal transducer activity (Gnat3)

Gnat3 (Mus musculus)

Pain Link Frequency Relevance Heat Bioavailability 28 90.32 tolerance 27 83.12 Potency 14 53.80 Angina 8 28.40 Glutamate 14 5.00 ischemia 7 5.00 alcohol 7 5.00

Disease Link Frequency Relevance Heat Increased Venous Pressure Under Development 17 94.92 Myocardial Infarction 1 29.20 Cv General 3 Under Development 1 28.40 Coronary Artery Disease 14 5.00 Targeted Disruption 7 5.00 Angina 7 5.00

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Protein

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Event

Anatomy

Negation

Speculation

Pain term

Disease term

Immunoblot analysis indicated that the majority of vascular ALDH2 is present in the cytoplasm, suggesting that mitochondrial biotransformation of GTN by ALDH2 plays a minor role in the overall vascular biotransformation of GTN by this enzyme.

Positive_regulation (biotransformation) of Gene_expression (biotransformation) of GTN

1) Confidence 0.13 Published 2003 Journal Mol. Pharmacol. Section Abstract Doc Link 14573760 Disease Relevance 0.26 Pain Relevance 0.13

As shown in Fig. 2A, GTN caused biphasic activation of sGC in the presence of both ALDH2 variants with apparent EC50 values of 3.4 ± 0.20 and 15 ± 1.5 ?

Positive_regulation (presence) of Gene_expression (caused) of GTN

2) Confidence 0.13 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2801295 Disease Relevance 0 Pain Relevance 0

As shown in Fig. 2A, GTN caused biphasic activation of sGC in the presence of both ALDH2 variants with apparent EC50 values of 3.4 ± 0.20 and 15 ± 1.5 ?

Positive_regulation (activation) of Gene_expression (caused) of GTN

3) Confidence 0.13 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2801295 Disease Relevance 0 Pain Relevance 0

At low GTN, the ALDH2-catalyzed reaction results in highly selective formation of 1,2-GDN, but this selectivity is largely lost at increasing GTN concentrations or in the presence of enzyme inhibitors (9).

Positive_regulation (increasing) of Gene_expression (concentrations) of GTN

4) Confidence 0.12 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2801295 Disease Relevance 0 Pain Relevance 0

This discrepancy reinforces our recent proposal that GTN denitration and bioactivation reflect two separate pathways of ALDH2-catalyzed GTN biotransformation, both of which involve formation of a thionitrate intermediate at Cys302 as initial reaction step (12).

Positive_regulation (bioactivation) of Gene_expression (denitration) of GTN

5) Confidence 0.12 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2801295 Disease Relevance 0 Pain Relevance 0.03

To obtain information on the effects of the nicotinamide and, in particular, Alda-1 on bioactivation of a pharmacologically relevant GTN concentration, the same set of experiments was performed with 1 ?

Positive_regulation (relevant) of Gene_expression (concentration) of GTN

6) Confidence 0.12 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2801295 Disease Relevance 0 Pain Relevance 0.05

m) was reached 120 ± 3.0 s after injection of GTN and rapidly decayed, whereas the maximum for ALDH2*2 (0.26 ± 0.03 ?

Positive_regulation (for) of Gene_expression (injection) of GTN

7) Confidence 0.12 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2801295 Disease Relevance 0 Pain Relevance 0

To obtain information on the effects of the nicotinamide and, in particular, Alda-1 on bioactivation of a pharmacologically relevant GTN concentration, the same set of experiments was performed with 1 ?

Positive_regulation (bioactivation) of Gene_expression (concentration) of GTN

8) Confidence 0.12 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2801295 Disease Relevance 0 Pain Relevance 0.05

General Comments

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