Pearson, RJ and Butler, A (2021) Glyceryl Trinitrate: History, Mystery, and Alcohol Intolerance. Molecules, 26 (21). 6581 - 6581. ISSN 1420-3049

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Glyceryl trinitrate (GTN) is one of the earliest known treatments for angina with a fascinating history that bridges three centuries. However, despite its central role in the nitric oxide (NO) story as a NO-donating compound, establishing the precise mechanism of how GTN exerts its medicinal benefit has proven to be far more difficult. This review brings together the explosive and vasodilatory nature of this three-carbon molecule while providing an update on the likely in vivo pathways through which GTN, and the rest of the organic nitrate family, release NO, nitrite, or a combination of both, while also trying to explain nitrate tolerance. Over the last 20 years the alcohol detoxification enzyme, aldehyde dehydrogenase (ALDH), has undoubtedly emerged as the front runner to explaining GTN's bioactivation. This is best illustrated by reduced GTN efficacy in subjects carrying the single point mutation (Glu504Lys) in ALDH, which is also responsible for alcohol intolerance, as characterized by flushing. While these findings are significant for anyone following the GTN story, they appear particularly relevant for healthcare professionals, and especially so, if administering GTN to patients as an emergency treatment. In short, although the GTN puzzle has not been fully solved, clinical study data continue to cement the importance of ALDH, as uncovered in 2002, as a key GTN activator.

Item Type: Article
Additional Information: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
Uncontrolled Keywords: glyceryl trinitrate; NO-donors; organic nitrates; nitric oxide; aldehyde dehydrogenase; nitrate tolerance
Subjects: R Medicine > R Medicine (General)
R Medicine > R Medicine (General) > R735 Medical education. Medical schools. Research
R Medicine > RA Public aspects of medicine
Divisions: Faculty of Medicine and Health Sciences > School of Pharmacy and Bioengineering
Depositing User: Symplectic
Date Deposited: 04 Nov 2021 15:43
Last Modified: 14 Feb 2022 10:07

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