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Variable glyceryl dinitrate formation as a function of glutathione S-transferase
Biological & Pharmaceutical Bulletin
|August 1, 1996
Summary
Glutathione S-transferases (GSTs) metabolize nitroglycerin (GTN) into glyceryl dinitrates (GDNs). This study reveals that alpha and mu GSTs exhibit distinct substrate specificities, influencing the specific GDN isomers formed during GTN breakdown.
Area of Science:
- Biochemistry
- Pharmacology
- Enzymology
Background:
- Nitroglycerin (GTN) is a primary treatment for angina pectoris.
- Glutathione S-transferases (GSTs) are known to metabolize GTN into glyceryl dinitrates (GDNs).
Purpose of the Study:
- To investigate the substrate specificity of different GST families towards GTN.
- To determine how alpha and mu GSTs differentially process GTN.
Main Methods:
- Isolation of alpha and mu GSTs from porcine liver and intestinal mucosa.
- Utilized CM-cellulose and glutathione-affinity column chromatography for enzyme purification.
- Analyzed the products of GTN metabolism by alpha and mu GSTs.
Main Results:
- Mu GSTs degraded GTN, preferentially forming 1,3-GDN over 1,2-GDN (ratio 0.61).
- Alpha GSTs metabolized GTN, producing twice as much 1,2-GDN as 1,3-GDN.
- Demonstrated distinct substrate specificities between alpha and mu GSTs for GTN.
Conclusions:
- Two major GST families, alpha and mu, are involved in GTN metabolism.
- These GSTs exhibit differential hydrolysis of nitrogroups within the GTN molecule.
- Understanding these specificities could inform GTN drug development and metabolism studies.