INT137334

Context Info Confidence 0.41 First Reported 2004 Last Reported 2010 Negated 2 Speculated 1 Reported most in Body Documents 8 Total Number 12 Disease Relevance 0.61 Pain Relevance 0.28

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

Gnat3 (Mus musculus)

Pain Link Frequency Relevance Heat Potency 10 100.00 Bioavailability 22 83.96 Angina 11 83.40 Calcium channel 1 82.96 addiction 25 52.16 tolerance 85 46.00 agonist 1 44.80 Glutamate 10 5.00 bradykinin 8 5.00 alcohol 6 5.00

Disease Link Frequency Relevance Heat Increased Venous Pressure Under Development 36 99.16 Emergencies 2 95.60 Adverse Drug Reaction 1 84.16 Angina 6 83.40 Hypoxia 1 45.84 Stress 12 45.36 Erectile Dysfunction 3 26.32 Hypertension 43 5.00 Disease 11 5.00 Coronary Artery Disease 10 5.00

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

The actions and interactions of GTN are explored as a guide for nurses to keep in mind when administering GTN to the patient in a cardiovascular emergency.

GTN Binding (interactions) of associated with emergencies

1) Confidence 0.41 Published 2006 Journal Contemp Nurse Section Abstract Doc Link 16863416 Disease Relevance 0.34 Pain Relevance 0.08

A substantial decrease of the dissociation constant for GTN in the presence of NAD+ seems to be an implausible explanation.4 It is more likely that NAD+ binding exposes a target to GTN that is poorly accessible in the absence of the cofactor.

GTN Binding (target) of

2) Confidence 0.21 Published 2008 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2576553 Disease Relevance 0 Pain Relevance 0

We propose that, in addition to the DTT-reversible oxidation of the active site cysteine by GTN, the oxidized cysteinyl and/or some other active site residues may engage in a secondary reaction with GTN to yield an enzyme species that does not support dehydrogenation and is not reduced by DTT.

GTN Binding (engage) of

3) Confidence 0.16 Published 2008 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2576553 Disease Relevance 0 Pain Relevance 0

m GTN at pH 7.5 resulted in complete inactivation of acetaldehyde dehydrogenation, whereas the enzyme remained active after preincubation in the absence of GTN.

GTN Neg (absence) Binding (absence) of

4) Confidence 0.16 Published 2008 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2576553 Disease Relevance 0 Pain Relevance 0.03

Importantly, ALDH2-catalyzed GTN reduction was partly inactivated by preincubation with GTN, suggesting that the inactivation of GTN reduction is also partly irreversible.

GTN Binding (preincubation) of

5) Confidence 0.16 Published 2008 Journal The Journal of Biological Chemistry Section Abstract Doc Link PMC2576553 Disease Relevance 0 Pain Relevance 0

A secondary reaction, in which GTN or one of its metabolites reacts with an oxidized or nitrated thiol before generation of the disulfide can occur, might result in irreversible formation of thiol sulfinate and sulfonate products (6, 14).

GTN Binding (reacts) of

6) Confidence 0.15 Published 2008 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2576553 Disease Relevance 0 Pain Relevance 0

Formation of 1,3-GDN appears to occur through a nonspecific side reaction of the enzyme, which does not involve binding of GTN to the catalytic site because it is insensitive to substrate-competitive inhibitors.

GTN Binding (binding) of

7) Confidence 0.11 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2801295 Disease Relevance 0 Pain Relevance 0

Determination of GTN-derived NO in the Presence of ALDH2

GTN Neg (NO) Spec (Determination) Binding (Determination) of

8) Confidence 0.09 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2801295 Disease Relevance 0 Pain Relevance 0

It was one of the goals of the present study to find out whether Alda-1 might be useful as a lead compound for the development of drugs improving the potency of GTN in subjects carrying the ALDH2*2 allele, but our data clearly argue against this possibility.

GTN Binding (potency) of associated with potency

9) Confidence 0.09 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2801295 Disease Relevance 0 Pain Relevance 0.05

As expected from the lower GTN affinity of the mutant, the rates of cGMP formation were much lower in the presence of ALDH2*2.

GTN Binding (affinity) of

10) Confidence 0.08 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2801295 Disease Relevance 0 Pain Relevance 0.04

The present results indicate that Alda-1 stimulates established ALDH2 activities by improving NAD binding but does not improve the GTN binding affinity of the Asian variant.

GTN Binding (affinity) of

11) Confidence 0.08 Published 2010 Journal The Journal of Biological Chemistry Section Abstract Doc Link PMC2801295 Disease Relevance 0 Pain Relevance 0.04

trinitrate (GTN) was earlier believed to be due to its conversion

GTN Binding (trinitrate) of

12) Confidence 0.05 Published 2004 Journal Journal of Biomedicine and Biotechnology Section Body Doc Link PMC555773 Disease Relevance 0.27 Pain Relevance 0.04

General Comments

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